1 1

RESUME PERSONAL

Name: William J. Greenlee, Ph.D. Address: 115 Herrick Avenue, Teaneck, New Jersey, 07666 Telephone: Home - (201) 692-9712 Business – (201) 485-6230 Cell - (908) 463-5332 william@william-greenlee.com

PROFESSIONAL EXPERIENCE

MedChem Discovery Consulting, LLC, Teaneck, NJ

Principal, November, 2011 - present

Consulting services in Preclinical Drug Discovery; including Lead Identification

(Hit-to-Lead), Lead Optimization, Candidate Nomination, Preclinical Development,

Intellectural Properties Issues and Due Diligence.

Merck Research Laboratories, Rahway, NJ

Senior Director, Medicinal Chemistry, Rahway, N.J., August, 2010 to September 2011

Responsible for the design and synthesis of drug candidates in the Cardiovascular

and Metabolic Disease areas (50 chemists). Areas of focus included hypertension,

thrombosis and obesity/diabetes.

Merck Research Laboratories, Kenilworth, NJ

Vice President, Medicinal Chemistry, and Kenilworth Chemistry Site Head, Kenilworth,

N.J., November, 2009 to August, 2010.

Responsible for Chemical Research in Kenilworth in support of six Merck franchise

areas - Cardiovascular, Diabetes/Obesity, Neurosciences, Infectious Diseases,

Oncology and BRID (Bone, Respiratory, Immunology, Dermatology). Staff (220

chemists) comprised Medicinal Chemistry, Structural Chemistry, Radiochemistry

and Spectroscopy.

Schering-Plough Research Institute, Kenilworth, NJ

2 2

Vice President, CNS and Cardiovascular Chemistry and High-Throughput Synthesis,

May 2002 – November, 2009

Responsible for the design and synthesis of drug candidates in the CNS and

Cardiovascular/Metabolic Disease areas, and for Hit-to-Lead support for all SPRI

therapy areas (80 chemists). Provided overall direction to chemistry outsourcing

activities that employed 120 chemists at WuXi Pharmatech (Shanghai, China) and

30 chemists at AMRI (Albany, NY).

Senior Director, CNS and Cardiovascular Chemistry, September 1995 to May, 2002.

Responsible for the design and synthesis of drug candidates in support of the

cardiovascular and CNS therapy areas, and for the High-Throughput Synthesis

(HiTS) group (45-75 chemists).

Merck Research Laboratories, Rahway, NJ

Senior Director, Basic Medicinal Chemistry, August 1993 - August 1995.

Directed research in the design and synthesis of receptor antagonists and enzyme

inhibitors in the cardiovascular, inflammation and diabetes areas (15-25

chemists).

Director, Exploratory Chemistry Department, July 1989 - July 1993.

Directed research in the design and synthesis of receptor antagonists and enzyme

inhibitors in the cardiovascular, central nervous system, and inflammation areas

(15-25 chemists).

Assistant Director, Exploratory Chemistry Department, July, 1984 - July 1989.

Directed research projects in hypertension and diabetes (12-15 chemists).

Research Fellow, New Lead Discovery Department, September, 1981 - July, 1984.

Directed research in the design and synthesis of inhibitors of angiotensin-

converting enzyme, alanine racemase and D-Ala-D-Ala ligase.

Senior Chemist, New Lead Discovery Department, August, 1977 - August, 1981.

Design and synthesis of inhibitors of angiotensin-converting enzyme.

Chemical Samples Company (Dr. Kenneth W. Greenlee, President), Columbus, OH

Summer work in synthesis of hydrocarbons for catalog business (1966-1970).

Acetylene and olefin synthesis using standard reaction sequences in liquid

3 3

ammonia (24-Liter glass flasks). Gained experience in high-efficiency distillation

techniques, including column packing and maintenance.

EDUCATION

Columbia University, February, 1976 - July, 1977

National Institutes of Health Postdoctoral Fellow in Chemistry - Postdoctoral work with Professor Gilbert Stork on the total synthesis of cytochalasin B.

Harvard University, September, 1972 - February, 1976

National Science Foundation Predoctoral Fellow in Chemistry (September 1972 - August, 1975); Ph.D. in Chemistry (June, 1976) - Graduate research with Professor R. B. Woodward on the total synthesis of marasmic acid.

The Ohio State University, September, 1968 - June, 1972

B.S. in Chemistry (June, 1972), Summa Cum Laude and with Distinction. Undergraduate research with Professor Paul G. Gassman (Junior and Senior academic years, and summers of 1971, 1972).

SOCIETY MEMBERSHIPS

American Chemical Society

American Association for the Advancement of Science

Sigma Xi

Sino-American Pharmaceutical Association (SAPA)

ACADEMIC AND PROFESSIONAL HONORS

Research and Development Council of New Jersey 2009 Thomas Alva Edison

Patent Award (Emerging Technology category) – Adenosine A2A Receptor

Antagonist (preladenant).

Elected a Fellow of the American Chemical Society, July, 2009 (inaugural class).

Research and Development Council of New Jersey 2008 Thomas Alva Edison

Patent Award (Emerging Technology category) – Thrombin Receptor Antagonist

(vorapaxar).

Elected a Fellow of the American Association for the Advancement of Science

(AAAS) / Pharmaceutical Chemistry Division, October, 2007.

4 4

Inducted into the Medicinal Chemistry Hall of Fame of the American Chemical

Society Division of Medicinal Chemistry, August 2006 (one of first three medicinal

chemists given this honor).

Alfred Burger Award in Medicinal Chemistry, American Chemical Society, March

2004.

National Institutes of Health Postdoctoral Fellowship (February, 1976 - July,

1977).

National Science Foundation Graduate Fellowship (September, 1972 - August,

1975).

The American Institute of Chemists Award for the outstanding senior

undergraduate majoring in chemistry, The Ohio State University, 1972.

William L. Evans Memorial Award to an Outstanding Senior Student in Chemistry,

For Excellence in Scholarship and Leadership, The Ohio State University, 1972.

College of Arts and Sciences undergraduate research scholarship, The Ohio State

University, academic year 1971 - 1972.

National Science Foundation Undergraduate Research Program participant, The

Ohio State University, summers 1970, 1971 (Research Advisor, Prof. Paul G.

Gassman).

Member of Phi Beta Kappa and Phi Eta Sigma (freshman men's honorary society).

PROFESSIONAL ACTIVITIES

American Chemical Society, Division of Medicinal Chemistry - Vice Chair, 2000;

Long-Range Planning Committee (LRPC) Chair, 2000; Program Chair; 2001-2002;

Division Chair, 2003. Industrial Councilor (2009-2011) [elected positions]. Chair,

Predoctoral Fellowship Program Selection Committee, 2004. Section Editor

(Cardiovascular and Pulmonary), Annual Reports in Medicinal Chemistry, (1999 –

2004). Member, Division of Medicinal Chemistry Awards Nominating Committee,

2010 - 2011.

American Chemical Society, Division of Organic Chemistry - Executive Committee

Member-at-Large (2000-2003); Chair-Elect (2003); Chair (2004); Past Chair (2005);

Program Chair (2007-2008). 2011 National Organic Symposium Executive Officer

(2009-2011) [elected positions]. Technical Achievements in Organic Chemistry

Award Program, Selection Committee (2001), Organizer (2002 - 2003). Chair,

Division of Organic Chemistry Travel Award Program, 2006-2007. Member, DOC

Awards Committee, 2009. Member, Division of Organic Chemistry ACS Fellows

5 5

Nomination Committee (2009-2010). Co-organizer, Robert Burns Woodward

Memorial Symposium, A.C.S. National Meeting, Boston, MA, August 23, 2010.

Symposium Executive Officer and Co-Organizer, 42nd National Organic Chemistry

Symposium, Princeton University, June 5 – 9, 2011.

Other American Chemical Society Activities - Editorial Advisory Board, Journal of

Medicinal Chemistry (2001 – 2006); Perspectives Editor (April, 2006-present).

Editorial Advisory Board, ACS Medicinal Chemistry Letters (2010 – present).

Organized / Chaired 15 symposia for ACS National Meetings (ORGN, MEDI) during

2000-2010, including the Arthur C. Cope Award Symposium and other ACS

National Award symposia. American Chemical Society National Awards Selection

Committee, 2001-2003. Associate Member, American Chemical Society

Committee on Public Relations and Communications (2008-2009). Associate

Member, Committee on Divisional Activities (2010), Member (2011). Co-

Organizer, ACS PharmaLeaders Conference at Schering-Plough Research Institute,

Kenilworth, NJ, November 9-10, 2008.

Other Professional Activities - Chair, Gordon Research Conference on Medicinal

Chemistry, Colby-Sawyer College, August 3-9, 1997. Co-Organizer, annual Drew

Residential School in Medicinal Chemistry and Drew Residential School Special

Topics courses (2001 - present). Scientific Advisory Board, Rider University (2002

– 2011). Member, University of Kansas School of Pharmacy Executive Advisory

Council, 2005; 2010. Editorial Advisory Board, Medicinal Research Reviews (2002

– 2006). Section Co-Editor for Current Opinion in Drug Discovery and

Development (Current Drugs) (1999 - 2006). NIH/NIDDK Spring 2008 Board of

Scientific Counselors Review – Ad Hoc Member. Member of 2009 Sato

International Award Nominating Committee. Co-Organizer, Keystone Conference

on Small Molecule Drug Discovery, Whistler, British Columbia, Apr 20 - 25, 2010.

Section Head, "Drug Discovery & Design" Section, Faculty of 1000 Biology (2009 -

present). Member of the Advisory Board of the Institute of Chemical Biology and

Drug Discovery (ICB&DD) at Stony Brook University (2010 - ).

PUBLICATIONS

1. Paul G. Gassman and William J. Greenlee. Chemistry of Bent Bonds XXX. A

Simple Approach to Azulenes, Syn. Comm., 2, 395-398 (1972).

2. Paul G. Gassman and William J. Greenlee. Chemistry of Bent Bonds XXXVI.

Photolysis of Substituted Derivatives of 2,3-Diazabicyclo[3.1.0]-hex-2-ene. A

Simple Route to Certain Bicyclo[1.1.0]butanes, J. Amer. Chem. Soc., 95, 980-

982 (1973).

6 6

3. P. G. Gassman and W. J. Greenlee. Dideuteriodiazomethane, Org. Syn., 53, 38

(1973).

4. W. J. Greenlee and R. B. Woodward. Total Synthesis of Marasmic Acid, J. Amer.

Chem. Soc., 98, 6075 (1976).

5. W. J. Greenlee, D. Taub and A. A. Patchett. A General Synthesis of -Vinyl--

Amino Acids, Tetrahedron Letts., 3999 (1978).

6. G. Stork, Y. Nakahara, Y. Nakahara and W. J. Greenlee. Total Synthesis of

Cytochalasin B, J. Amer. Chem. Soc., 100, 9775 (1978).

7. A. A. Patchett, E. Harris, E. W. Tristram, M. J. Wyvratt, M. T. Wu, D. Taub, E. R.

Peterson, T. J. Ikeler, J. ten Broeke, L. G. Payne, D. L. Ondeyka, E. D. Thorsett,

W. J. Greenlee, N. S. Lohr, R. D. Hoffsommer, H. Joshua, W. V. Ruyle, J. W.

Rothrock. S. D. Aster, A. L. Maycock, F. M. Robinson and R. Hirschmann. A New

Class of Angiotensin-Converting Enzyme Inhibitors, Nature, 288, 280 (1980).

8. W. J. Greenlee and R. B. Woodward. Marasmic Acid I; Total Synthesis of (+/-)-

Isomarasmic Acid, Tetrahedron, 36, 3361 (1980).

9. W. J. Greenlee and R. B. Woodward. Marasmic Acid II; Total Synthesis of (+/-)-

Marasmic Acid. Tetrahedron, 36, 3366 (1980).

10. W. J. Greenlee and E. D. Thorsett. Mild Conversion of Carboxamides and

Carboxylic Acid Hydrazides to Acids and Esters, J. Org. Chem., 46, 5351 (1981).

11. E. D. Thorsett, E. E. Harris, E. R. Peterson, W. J. Greenlee, A. A. Patchett, E. H.

Ulm and T. C. Vassil. Phosphorous-Containing Inhibitors of Angiotensin-

Converting Enzyme, Proc. Natl. Acad. Sci. USA, 79, 2176 (1982).

12. W. J. Greenlee. Preparation of Substituted N-Carboxymethyl Dipeptides,

Tetrahedron Letts., 23, 3995 (1982).

13. W. J. Greenlee and D. G. Hangauer. Addition of Trimethylsilylcyanide to a-

Substituted Ketones: Catalyst Efficiency, Tetrahedron Letts., 24, 4559 (1983).

14. W. J. Greenlee. Synthesis of ,-Unsaturated Amino Acids by the Strecker

Reaction, J. Org. Chem., 49, 2632 (1984).

15. W. J. Greenlee, E. D. Thorsett, J. P. Springer and A. A. Patchett. Azapeptide

Inhibitors of Angiotensin-Converting Enzyme, Biochem. Biophys. Res.

Commun., 122, 791 (1984).

16. William J. Greenlee, Patricia L. Allibone, Debra S. Perlow, Arthur A. Patchett,

Edgar H. Ulm and Theodore C. Vassil. Angiotensin-Converting Enzyme

7 7

Inhibitors: Synthesis and Biological Activity of Acyltripeptide Analogs of

Enalapril, J. Med. Chem., 28, 434 (1985).

17. N. A. Thornberry, H. G. Bull, D. Taub, W. J. Greenlee, A. A. Patchett and E. H.

Cordes. 3-Halovinylglycines. Efficient Irreversible Inhibitors of E. Coli Alanine

Racemase, J. Amer. Chem. Soc., 109, 7543 (1987).

18. W. J. Greenlee. Renin Inhibitors, Pharmaceutical Research, 4, 364 (1987).

19. P. K. Chakravarty, P. Combs, A. Roth and W. J. Greenlee. An Efficient Synthesis

of -Amino--Ketophosphonates From -Amino Acids, Tetrahedron Letts., 28,

611 (1987).

20. Mark G. Bock, Robert M. DiPardo, Ben E. Evans, Kenneth E. Rittle, Joshua

Boger, Martin Poe, Bruce I. LaMont, Robert J. Lynch, Edgar H. Ulm, George P.

Vlasuk, William J. Greenlee and Daniel F. Veber. Renin Inhibitors. Statine-

Containing Tetrapeptides with Varied Hydrophobic Carboxy Termini, J. Med.

Chem., 30, 1853 (1987).

21. P. F. Schuda, W. J. Greenlee, P. K. Chakravarty, and P. Eskola. A short and

Efficient Synthesis of (3S,4S)-4-[(tert-Butoxycarbonyl)amino]-5-cyclohexyl-3-

hydroxypentanoic Acid Ethyl Ester, J. Org. Chem., 53, 873 (1988).

22. William J. Greenlee, James P. Springer and Arthur A. Patchett. Synthesis of an

Analog of Tabtoxin as a Potential Inhibitor of D-Alanine:D-Alanine Ligase (ADP

Forming), J. Med. Chem., 32, 165 (1989).

23. P. K. Chakravarty, W. J. Greenlee, W. H. Parsons, A. A. Patchett, P. Combs, A.

Roth, R. D. Busch and T. N. Mellin. (3-Amino-2-oxoalkyl)phosphonic Acids and

Their Analogues as Novel Inhibitors of D-Alanine-D-Alanine Ligase, J. Med.

Chem., 32, 1886 (1989).

24. Richard Saperstein, Pasquale P. Vicario, H. Vincent Strout, Edward Brady, Eve E.

Slater, William J. Greenlee, Debra L. Ondeyka, Arthur A. Patchett and David G.

Hangauer. Design of a Selective Insulin Receptor Tyrosine Kinase Inhibitor and

Its Effects on Glucose Uptake and Metabolism in Intact Cells, Biochemistry, 28,

5694 (1989).

25. William J. Greenlee. Renin Inhibitors, Med. Res. Rev., 10, 173 (1990).

26. S. E. deLaszlo, B. L. Bush, J. J. Doyle, W. J. Greenlee, D. G. Hangauer, T. A.

Halgren, R. J. Lynch, T. W. Schorn and P. K. S. Siegl. The Synthesis and Use of 3-

Amino-4-Phenyl-2-Piperidones and 4-Amino-2-Benzazepinones as

Conformationally-Restricted Phenylalanine Isosteres in Renin Inhibitors, in

Peptides, Chemistry, Structure and Biology, Proceedings of the Eleventh

8 8

American Peptide Symposium, J. E. Rivier and G. R. Marshall, eds., Escom

Science Publishers, B. V., Leiden, 1990, p. 409.

27. William J. Greenlee, Jan tenBroeke, Stephen E. deLaszlo, Prasun K.

Chakravarty, Valerie J. Camara, Kenneth J. Fitch, Carol S. Sarnella, Arthur A.

Patchett, Peter D. Williams, Debra S. Perlow, Daniel F. Veber, Robert J. Lynch,

John J. Doyle, Terry W. Shorn, John F. Strouse and Peter K. S. Siegl. Approaches

to Human Renin Inhibitors With Improved Bioavailability, in Peptides,

Chemistry, Structure and Biology, Proceedings of the Eleventh American

Peptide Symposium, J. E. Rivier and G. R. Marshall, eds., Escom Science

Publishers, B. V., Leiden, 1990, p. 411.

28. R. A. Jupp, B. M. Dunn, J. W. Jacobs, G. Vlasuk, K. E. Arcuri, D. F. Veber, D. S.

Perlow, L. S. Payne, J. Boger, S. deLaszlo, P. K. Chakravarty, J. tenBroeke, D. G.

Hangauer, D. Ondeyka, W. J. Greenlee and J. Kay. The Selectivity of Statine-

Based Inibitors Against Various Human Aspartic Proteinases, Biochem. J., 265,

871 (1990).

29. L. W. Schaffer, T. W. Schorn, R. J. Winquist, J. F. Strouse, L. Payne, P. K.

Chakravarty, S. E. deLaszlo, J. tenBroeke, D. F. Veber, W. J. Greenlee and P. K.

S. Siegl. Acute Hypotensive Responses to Peptide Inhibitors of Renin in

Conscious Monkeys: An Effect on Blood Pressure Independent of Plasma Renin

Inhibition, J. Hypertension, 8, 251 (1990).

30. W. J. Greenlee and A. E. Weber. Renin Inhibitors, Drug News and Perspectives,

4, 332 (1991).

31. W. J. Greenlee and Peter K. S. Siegl. Angiotensin / Renin Modulators, Annual

Reports in Medicinal Chemistry, Vol. 26, Chapter 7, pp 63-72 (1991).

32. R. A. Rivero and W. J. Greenlee. The Synthesis of Novel Macrocyclic Inhibitors

of Human Renin, Tetrahedron Letts., 32, 2453 (1991).

33. R. A. Rivero, W. J. Greenlee and A. A. Patchett. Sulfones as Peptide Bond

Isosteres, Tetrahedron Letts., 32, 5263 (1991).

34. A. E. Weber, T. A. Halgren, J. J. Doyle, R. J. Lynch, P. K. S. Siegl, W. H. Parsons,

W. J. Greenlee and A. A. Patchett. Design and Synthesis of P2-P2’-Linked

Macrocyclic Human Renin Inhibitors, J. Med. Chem., 34, 2692 (1991).

35. N. B. Mantlo, P. K. Chakravarty, D. L. Ondeyka, P. K. S. Siegl, R. S. Chang, V. J.

Lotti, K. A. Faust, T.-B. Chen, T. W. Schorn, C. S. Sweet, S. E. Emmert, A. A.

Patchett and W. J. Greenlee. Potent, Orally Active Imidazo[4,5-b]pyridine-

Based Angiotensin II Antagonists, J. Med. Chem., 34, 2919 (1991).

9 9

36. P. D. Williams, L. S. Payne, D. S. Perlow, M. K. Holloway, P. K. S. Siegl, T. W.

Schorn, R. J. Lynch, J. J. Doyle, J. F. Strouse, G. P. Vlasuk, K. Hoogsteen, J. P.

Springer, B. L. Bush, T. A. Halgren, J. tenBroeke, W. J. Greenlee, A. D. Richards,

J. Kay and D. F. Veber. Design of Renin Inhibitors Containing Conformationally-

Restricted Mimetics of the P1-P1’ and P1 Through P2’ Sites, Structure and

Function of the Aspartic Proteinases, B. M. Dunn, Ed., Plenum Press, New York,

1991, pp 325-334.

37. W. T. Ashton, C. L. Cantone, L. C. Meurer, R. L. Tolman, W. J. Greenlee, A. A.

Patchett, R. J. Lynch, T. W. Schorn, J. F. Strouse and P. K. S. Siegl. Renin

Inhibitors Containing C-Termini Derived from Mercaptoheterocycles, J. Med.

Chem., 35, 2103 (1992).

38. S. E. de Laszlo, B. L. Bush, J. J. Doyle, W. J. Greenlee, D. G. Hangauer, T. A.

Halgren, R. J. Lynch, T. W. Schorn and P. K. S. Siegl. Synthesis and Use of 3-

Amino-4-phenyl-2-piperidones and 4-Amino-2-benzazepin-3-ones as

Conformationally Restricted Phenylalanine Isosteres in Renin Inhibitors, J.

Med. Chem., 35, 83 (1992).

39. W. J. Greenlee and Peter K. S. Siegl. Angiotensin / Renin Modulators, Annual

Reports in Medicinal Chemistry, Vol. 27, Chapter 7, pp 59-68 (1992).

40. P. K. S. Siegl, R. S. L. Chang, N. B. Mantlo, P. K. Chakravarty, W. J. Greenlee, A.

A. Patchett, C. S. Sweet and V. J. Lotti. In Vivo Pharmacology of L-158,809, a

New Highly Potent and Selective Nonpeptide Angiotensin II (AII) Receptor

Antagonist, J. Pharm. Exp. Therapeut., 262, 139, 1992.

41. R. S. L. Chang, P. K. S. Siegl, B. V. Clineschmidt, N. B. Mantlo, P. K. Chakravarty,

W. J. Greenlee, A. A. Patchett and V. J. Lotti. In Vitro Pharmacology of L-

158,809, a New Highly Potent and Selective Nonpeptide Angiotensin II (AII)

Receptor Antagonist, J. Pharm. Exp. Therapeut., 262, 133, 1992.

42. W. T. Ashton, C. L. Cantone, R. L. Tolman, W. J. Greenlee, R. J. Lynch, T. W.

Schorn, J. F. Strouse and P. K. S. Siegl. Renin Inhibitors With C-Termini Derived

from Amides and Esters of -Mercaptoalkanoic Acids, J. Med. Chem., 35, 2772

(1992).

43. R. A. Rivero, P. K. Chakravarty, R. Chen, W. J. Greenlee, A. Rosegay and R.

Simpson, The Synthesis of [3H]-losartan, [3H]-L-158,641 and [3H]-L-158,809.

Bioorganic Med. Chem. Letts., 3, 557 (1993).

44. Eric E. Allen, Stephen E. deLaszlo, Song X. Huang, Carol S. Quagliato, William J.

Greenlee, Raymond, Tsing-Bau Chen, Kristie A. Faust, V. J. Lotti,

Quinazolinones 1: Design and Synthesis of Potent Quinazolinone-Containing

10 10

AT1-Selective Angiotensin II Receptor Antagonists, Bioorg. Med. Chem. Letts.,

3, 1293 (1993).

45. Stephen E. de Laszlo, Eric E. Allen, Carol S. Quagliato, William J. Greenlee,

Arthur A. Patchett, Robert B. Nachbar, Peter K. S. Siegl, Raymond S. Chang,

Salah D. Kivlighn, Terry S. Schorn, Kristie A. Faust, Tsing-Bau Chen, Gloria J.

Zingaro, Victor J. Lotti, Quinazolinones 2: QSAR and In Vivo Characterization of

AT1-Selective AII Antagonists, Bioorg. Med. Chem. Letts., 3, 1299 (1993).

46. Theresa M. Williams, Terrence C. Ciccarone, Suzanne C. MacTough, Clarence S.

Rooney, Suresh K. Balani, Jon H. Condra, Emilio A. Emini, Mark E. Goldman,

William J. Greenlee, Laura R. Kauffman, Julie A. O'Brien, Vinod V. Sardana,

William A. Schleif, Anthony D. Theoharides, and Paul S. Anderson. 5-Chloro-3-

(phenylsulfonyl)indole-2-carboxamide: A Novel, Non-Nucleoside Inhibitor of

HIV-1 Reverse Transcriptase, J. Med. Chem., 36, 1291 (1993).

47. Linda L. Chang, Wallace T. Ashton, Kelly L. Flanagan, Robert A. Strelitz, Malcolm

MacCoss, William J. Greenlee, Raymond S. L. Chang, Victor J. Lotti, Kristie A.

Faust, Tsing-Bau Chen, Patricia Bunting, Gloria J. Zingaro, Salah D. Kivlighn and

Peter K. S. Siegl. Triazolinones as Nonpeptide Angiotensin II Antagonists. 1.

Synthesis and Evaluation of Potent 2,4,5-Trisubstituted Triazolinones, J. Med.

Chem., 36, 2558 (1993).

48. W. T. Ashton, S. M. Hutchins, W. J. Greenlee, G. A. Doss, R. S. L. Chang, V. J.

Lotti, K. A. Faust, T.-B. Chen, G. J. Zingaro, S. D. Kivlighn and P. K. S. Siegl.

Nonpeptide Angiotensin II Antagonists Derived From 1H-Pyrazole-5-

carboxylates and 4-Aryl-1H-imidazole-5-carboxylates, J. Med. Chem., 36, 3595

(1993).

49. Peter K. S. Siegl, and William J. Greenlee. Challenges and Progress Toward the

Development of Orally Active Renin Inhibitors, Curr. Opin. Invest. Drugs, 2, 931

(1993).

50. M. T. Wu, T. J. Ikeler, W. T. Ashton, R. S. L. Chang, V. J. Lotti and W. J. Greenlee.

Synthesis and Structure-Activity Relationships of a Novel Series of Non-peptide

AT2 Selective Angiotensin II Receptor Antagonists, Bioorg. Med. Chem. Letts.,

3, 2023 1993.

51. S. E. de Laszlo, C. S. Quagliato, W. J. Greenlee, A. A. Patchett, R. S. L. Chang, V.

J. Lotti, T. B. Chen, S. A. Scheck, K. A. Faust, S. D. Kivlighn, T. S. Schorn, G. J.

Zingaro and P. K. S. Siegl. L-159,689, a Potent, Orally-active, Balanced Affinity

Antagonist of the Angiotensin II AT1 and AT2 Receptors, J. Med. Chem., 36,

3207 (1993).

11 11

52. Sander G. Mills, Mu Tsu Wu, Malcolm MacCoss, Richard J. Budhu, Conrad P.

Dorn, Jr., Margaret A. Cascieri, Sharon Sadowski, Catherine D. Strader, William

J. Greenlee, 1,4-Diacylpiperazine-2-(S)-[N-Aminoalkyl)carboxamides] as Novel,

Potent Substance P Receptor Antagonists, Bioorg. Med. Chem. Letts., 3, 2707

(1993).

53. Lihu Yang, Ann E. Weber, William J. Greenlee and Arthur A. Patchett,

Marcocyclic Renin Inhibitors: Synthesis of a Subnanomolar, Orally Active

Cysteine Derived Inhibitor, Tetrahedron Letts., 34, 7035 (1993).

54. D. S. Dhanoa, S. W. Bagley, R. S. L. Chang, V. J. Lotti, T.-B. Chen, S. D. Kivlighn,

G. J. Zingaro, P. K. S. Siegl, P. K. Chakravarty, A. A. Patchett, W. J. Greenlee,

(Dipropylphenoxy)phenylacetic Acids: A New Generation of Nonpeptide

Angiotensin II Receptor Antagonists, J. Med. Chem., 36, 3738 (1993).

55. D. S. Dhanoa, S. W. Bagley, R. S. L. Chang, V. J. Lotti, T.-B. Chen, S. D. Kivlighn,

G. J. Zingaro, P. K. S. Siegl, A. A. Patchett and W. J. Greenlee, Non-Peptide

Angiotensin II Receptor Antagonists. 1. Design, Synthesis and Biological Activity

of N-Substituted Indoles and Dihydroindoles, J. Med. Chem., 36, 4230 (1993).

56. D. S. Dhanoa, S. W. Bagley, R. S. L. Chang, V. J. Lotti, T.-B. Chen, S. D. Kivlighn,

G. J. Zingaro, P. K. S. Siegl, P. K. Chakravarty, A. A. Patchett, W. J. Greenlee,

Non-Peptide Angiotensin II Receptor Antagonists. 2. Design, Synthesis and

Biological Activity of N-Substituted (Phenylamino)phenylacetic Acids and

Acylsulfonamides, J. Med. Chem., 36, 4239 (1993).

57. Nathan B. Mantlo, Dooseop Kim, Debra Ondeyka, Raymond S. L. Chang, Salah

D. Kivlighn, Peter K. S. Siegl and William J. Greenlee, Potent Imidazo[4,5-

b]pyridine Angiotensin II Antagonists Which Exhibit Balanced Affinity to the

AT1 and AT2 Receptor Subtypes, Bioorg. Med. Chem. Letts., 4, 17 (1994).

58. D. Kim, N. B. Mantlo, R. S. L. Chang, S. D. Kivlighn and W. J. Greenlee,

Evaluation of Heterocyclic Acid Equivalents as Tetrazole Replacements in

Imidazopyridine-Based Nonpeptide Angiotensin II Receptor Antagonists,

Bioorg. Med. Chem. Letts., 4, 41 (1994).

59. Elizabeth M. Naylor, Prasun K. Chakravarty, Colleen A. Costello, Raymond S.

Chang, Tsing-Bau Chen, Kristie A. Faust, Victor J. Lotti, Salah D. Kivlighn, Gloria

J. Zingaro, Peter K. S. Siegl, Pancras C. Wong, David J. Carini, Ruth R. Wexler,

Arthur A. Patchett and William J. Greenlee. Potent Imidazole Angiotensin II

Antagonists: Acylsulfonamides and Acylsulfamides as Tetrazole Replacements,

Bioorg. Med. Chem. Letts., 4, 69 (1994).

12 12

60. P. K. Chakravarty, R. A. Strelitz, T.-B. Chen, R. S. L. Chang, V. J. Lotti, G. J.

Zingaro, T. W. Schorn, S. D. Kivlighn, P. K. S. Siegl, A. A. Patchett, W. J.

Greenlee, Quinazolinone Biphenyl Acylsulfonamides: A Potent New Class of

Angiotensin-II Receptor Antagonists, Bioorg. Med. Chem. Letts., 4, 75 (1994).

61. T. W. Glinka, S. E. de Laszlo, P. K. S. Siegl, R. S. L. Chang, S. D. Kivlighn, T. S.

Schorn, K. A. Faust, T. B. Chen, G. J. Zingaro, V. J. Lotti and W. J. Greenlee. A

New Class of Balanced AT1/AT2 Angiotensin II Antagonists: Quinazolinone AII

Antagonists with Acylsulfonamide and Sulfonylcarbamate Acidic

Functionalities, Bioorg. Med. Chem. Letts., 4, 81 (1994).

62. L. L. Chang, W. T. Ashton, K. L. Flanagan, E. M. Naylor, P. K. Chakravarty, A. A.

Patchett, W. J. Greenlee, T.-B. Chen, K. A. Faust, L. W. Schaffer, T. W. Schorn,

G. J. Zingaro, R. S. L. Chang, V. J. Lotti, S. D. Kivlighn and P. K. S. Siegl.

Triazolinones as Nonpeptide Angiotensin II Antagonists. II. Discovery of a

Potent and Orally-Active Triazolinone Acylsulfonamide, Bioorg. Med. Chem.

Letts., 4, 115 (1994).

63. N. J. Kevin, R. A. Rivero, W. J. Greenlee, R. S. L. Chang and T. B. Chen,

Substituted Phenylthiophene Benzoylsulfonamides with Potent Binding Affinity

to Angiotensin II AT1 and AT2 Receptors, Bioorg. Med. Chem. Letts., 4, 189

(1994).

64. D. Kim, N. B. Mantlo, J. R. Tata, K. Fitch, D. Dhanoa, K. Owens, D. Levorse, P. K.

S. Siegl, R. S. L. Chang, T. Chen, S. Scheck, G. J. Zingaro, S. D. Kivlighn and W. J.

Greenlee, Acidic Phenol: A New Class of Potent Nonpeptide Angiotensin II

Receptor Antagonists, Bioorg. Med. Chem. Letts., 4, 207 (1994).

65. Thomas F. Walsh, Kenneth J. Fitch, Malcolm MacCoss, Raymond S. L. Chang,

Salah D. Kivlighn, Victor J. Lotti, Peter K. S. Siegl, Arthur A. Patchett and William

J. Greenlee, Synthesis of New Imidazo[1,2-b]pyridazine Isosteres of Potent,

Imidazo[4,5-b]pyridine Angiotensin II Antagonists, Bioorg. Med. Chem. Letts.,

4, 219 (1994).

66. R. A. Rivero, W. J. Greenlee, R. S. L. Chang, Substituted 1,3-Benzodioxole and

1,3-Benzodithiole-2-carboxylates and Their Tetrazole Analogs with Potent

Binding Affinity to the Angiotensin II AT1 Receptor, Bioorg. Med. Chem. Letts.,

4, 747 (1994).

67. Thomasz W. Glinka, Stephen E. de Laszlo, Jennifer Tran, Raymond S. Chang,

Tsing-Bau Chen, Victor J. Lotti and William J. Greenlee, L-161,638, A Potent

Selective Quinazolinone Angiotensin II Binding Inhibitor, Bioorg. Med. Chem.

Letts., 4, 1479 (1994).

13 13

68. D. S. Dhanoa, S. W. Bagley, R. S. L. Chang, V. J. Lotti, T. Chen, S. D. Kivlighn, G. J.

Zingaro, P. K. S. Siegl and W. J. Greenlee, Nonpeptide Angiotensin II (AII)

Receptor Angtagonists, N-Substituted Indole, Dihydroindole,

Phenylaminophenylacetic Acid and Acylsulfonamide-Based AII Receptor

Antagonists, in Peptides, Chemistry, Structure and Biology, Proceedings of the

Thirteenth American Peptide Symposium, Robert S. Hodges and John A. Smith,

eds., Escom Science Publishers, B. V., Leiden, 1994, p. 296.

69. R. S. L. Chang, R. J. Bendesky, T. B. Chen, K. A. Faust, P. J. Kling, S. A. O'Malley,

E. M. Naylor, P. K. Chakravarty, A. A. Patchett, W. J. Greenlee, B. V.

Clineschmidt and V. J. Lotti, In Vitro Pharmacology of MK-996, A New Potent

And Selective Angiotensin II (AT1) Receptor Antagonist, Drug Dev. Res., 32, 161

(1994).

70. Thomasz W. Glinka, Stephen E. de Laszlo, Peter K. S. Siegl, Raymond S. Chang,

Salah D. Kivlighn, Terry S. Schorn, Kristie A. Faust, Tsing-Bau Chen, Gloria J.

Zingaro, Victor J. Lotti and William J. Greenlee, Development of Angiotensin II

Antagonists with Equipotent Affinity for Human AT1 and AT2 Receptor

Subtypes, Bioorg. Med. Chem. Letts., 4, 2337 (1994).

71. L. L. Chang, W. T. Ashton, K. L. Flanagan, T. B. Chen, S. O'Malley, G. Zingaro, P.

K. Siegl, S. D. Kivlighn, R. S. L. Chang and W. J. Greenlee, Triazolinone

Biphenylacylsulfonamides as Angiotensin II Receptor Antagonists With High

Affinity For Both The AT1 and AT2 Subtypes, J. Med. Chem., 37, 4464 (1994).

72. L. L. Chang, W. T. Ashton, K. L. Flanagan, R. A. Rivero, T.-B. Chen, S. S. O'Malley,

G. J. Zingaro, S. D. Kivlighn, P. K. S. Siegl, V. J. Lotti, R. S. L. Chang and W. J.

Greenlee, Potent Triazolinone-Based Angiotensin II Receptor Antagonists with

Equivalent Affinity for Both the AT1 and AT2 Subtypes, Bioorg. Med. Chem.

Letts., 4, 2787 (1994).

73. Prasun K. Chakravarty, Elizabeth M. Naylor, Anna Chen, Raymond S. L. Chang,

Tsing-Bau Chen, Kristie A. Faust, Victor J. Lotti, Salah D. Kivlighn, Robert A.

Gable, Gloria J. Zingaro, Terry W. Schorn, Linda W. Schaffer, Theodore P.

Broten, Peter K. S. Siegl, Arthur A. Patchett and William J. Greenlee, MK-996 (L-

159,282), A Highly Potent, Orally Active Imidazo[4,5-b]Pyridine Biphenyl

Acylsulfonamide: A New AT1 Selective Angiotensin II Receptor Antagonist, J.

Med. Chem., 37, 4068 (1994).

74. Siv A. Hjorth, Hans T. Schambye, William J. Greenlee and Thue W. Schwartz,

Identification of Peptide Binding Residues in the Extracellular Domains of the

AT1 Receptor, J. Biol. Chem., 269, 30953 (1994).

14 14

75. Kristine Prendergast, Kym Adams, William J. Greenlee, Robert B. Nachbar,

Arthur A. Patchett and Dennis J. Underwood, Derivation of a 3D

Pharmacophore Model for the Angiotensin-II Site One Receptor, J. Comput-

Aided Mol. Design, 8, 491 (1994).

76. Dennis J. Underwood, Ralph Rivero, William Greenlee, Arthur Patchett and

Kristine Prendergast, Structural Model of Antagonist and Agonist Binding to

the Angiotensin-II, AT1 Subtype, G-Protein Coupled Receptor, Chemistry and

Biology, Chemistry & Biology, 1, 211 (1994).

77. Signe Perlman, Hans T. Schambye, Ralph A. Rivero, William J. Greenlee, Siv A.

Hjorth and Thue W. Schwartz, Non-peptide Angiotensin Agonist, J. Biol. Chem.,

270, 1493 (1995).

78. Salah D. Kivlighn, Gloria J. Zingaro, Robert A. Gabel, Theodore P. Broten, Terry

W. Schorn, Linda W. Schaffer, Elizabeth M. Naylor, Prasun K. Chakravarty,

Arthur A. Patchett, William J. Greenlee and Peter K. S. Siegl, In Vivo

Pharmacology of a Novel AT1 Selective Angiotensin II Receptor Antagonist,

Am. J. Hypertens., 8, 58 (1995).

79. K. J. Fitch, T. F. Walsh, A. A. Patchett, R. S. L. Chang, P. K. S. Siegl, K. A. Faust, T.

B. Chen, V. J. Lotti, S. D. Kivlighn, G. J. Zingaro and W. J. Greenlee, Bioorg. Med.

Chem. Letts., 5, 155 (1995).

80. Salah D. Kivlighn, Gloria J. Zingaro, Ralph A. Rivero, William R. Huckle, Victor J.

Lotti, Raymond S. L. Chang, Terry W. Schorn, Nancy Kevin, Robert G. Johnson,

Jr., William J. Greenlee and Peter K. S. Siegl, Discovery of L-162,313: A

Nonpeptide That Mimics the Biological Actions of Angiotensin-II, Am. J. Physiol,

268, R820 (1995).

81. T. F. Walsh, K. J. Fitch, R. S. L. Chang, K. A. Faust, T.-B. Chen, S. D. Kivlighn, G. J.

Zingaro, V. J. -

Phenoxyphenylacetic Acid Derived Angiotensin II Antagonists With Low

Nanomolar AT1/ AT2 Receptor Subtype Affinity (Part II), Bioorg. Med. Chem.

Letts., 5, 1151 (1995).

82. T. F. Walsh, K. J. Fitch, D. L. Williams, K. L. Murphy, N. A. Nolan, D. J. Pettibone,

R. S. L. Chang, S. O'Malley, B. V. Clineschmidt, D. F. Veber, W. J. Greenlee,

Potent, Dual Antagonists of Endothelin and Angiotensin II Receptors Derived

From -Phenoxyphenylacetic Acids (Part III), Bioorg. Med. Chem. Letts., 5,

1155 (1995).

83. W. T. Ashton,* L. L. Chang, K. L. Flanagan, N. B. Mantlo, D. L. Ondeyka, D. Kim,

S. E. de Laszlo, T. W. Glinka, R. A. Rivero, N. J. Kevin, R. S. L. Chang, P. K. S. Siegl,

15 15

S. D. Kivligh, W. J. Greenlee, AT1/AT2-Balanced Angiotensin II Antagonists, Eur.

J. Med. Chem., 30 (Suppl.), 255S, 1995.

84. S. E. de Laszlo, R. S. Chang, T.-B. Chen, K. A. Faust, W. J. Greenlee, S. D. Kivlighn,

V. J. Lotti, S. S. O'Malley, T. W. Schorn, P. K. S. Siegl, J. Tran and G. J. Zingaro,

The SAR of 6-(N-Alkyl-N-Acyl)-2-Propyl-3-[(2-Tetrazol-5-yl)bipheny-4-

yl)methyl]-Quinazolinones as Balanced Affinity Antagonists of the Human AT1

and AT2 Receptors, Bioorg. Med. Chem. Letts., 5, 1359 (1995).

85. R. A. Rivero, W. J. Greenlee, P. D. Williams, G. R. Kieczykowski and D. L.

Williams Jr., Discovery of Substituted 8,9-Dicarboxydibenzo [2,3:5,6] Bicyclo

[5.2.0] Nonan-4-ones with Moderate Binding Affinity to the Endothelin ETA

and ETB Receptors, Bioorg. Med. Chem. Letts., 5, 1401 (1995).

86. R. A. Gabel, S. D. Kivlighn, G. J. Zingaro, T. W. Schorn, L. W. Schaffer, W. T.

Ashton, L. L. Chang, K. Flanagan, W. J. Greenlee and P. K. S. Siegl, In Vivo

Pharmacology of L-159,913, A New Highly Potent and Selective Nonpeptide

Angiotensin II Receptor Antagonist, Clin. Exper. Hypertens., 17, 931 (1995).

87. R. S. L. Chang, V. J. Lotti, T.-B. Chen, K. A. Faust, P. J. Kling, S. A. O’Malley, S. D.

Kivlighn, P. K. S. Siegl, D. Ondeyka, W. J. Greenlee, N. B. Mantlo, In Vitro

Pharmacology of an Angiotensin AT1 Receptor Antagonist with Balanced

Affinity for Angiotensin AT2 Receptors, Eur. J. Pharmacol., 294, 429 (1995).

88. S. D. Kivlighn, G. J. Zingaro, R. A. Gabel, T. P. Broten, R. S. L. Chang, D. L.

Ondeyka, N. B. Mantlo, R. E. Gibson, W. J. Greenlee, P. K. Siegl, In Vivo

Pharmacology of an Angiotensin AT1 Receptor Antagonist with Balanced

Affinity for Angiotensin AT2 Receptors, Eur. J. Pharmacol., 294, 439 (1995).

89. L. L. Chang, W. J. Greenlee, Angiotensin II Receptor Antagonists: Nonpeptides

with Equivalent High Affinity for Both the AT1 and AT2 Subtypes, Curr. Pharm.

Des., 1, 407 (1995).

90. D. L. Williams, Jr., K. L. Murphy, N. A. Nolan, J. A. O’Brien, D. J. Pettibone, S. D.

Kivlighn, S. M. Krause, E. V. Lis, Jr., G. J. Zingaro, R. A. Gabel, F. C. Clayton, P. K.

S. Siegl, K. Zhang, J. Naue, K. Vyas, T. F. Walsh, F. K. Fitch, P. K. Chakravarty, W.

J. Greenlee and B. V. Clineschmidt, Pharmacology of L-754,142, a Highly

Potent, Orally Active, Nonpeptidyl Endothelin Antagonist, J. Pharmacol. Exp.

Therapeut., 275, 1518 (1995).

91. R. R. Wexler, W. J. Greenlee, J. D. Irvin, M. R. Goldberg, K. Prendergast, R. D.

Smith, P. B. M. W. M. Timmermans, Nonpeptide Angiotensin II Receptor

Antagonists: The Next Generation in Antihypertensive Therapy, J. Med. Chem.,

39, 625 (1996).

16 16

92. W. Huckle, M. D. Drag, W. R. Acker, M. Powers, R. C. McFall, D. J. Holder, T.

Fujita, I. I. Stabilito, D. Kim, D. L. Ondeyka, N. B. Mantlo, R. S. L. Chang, C. F.

Reilly, R. S. Schwartz, W. J. Greenlee, R. G. Johnson, Effects of Subtype-

Selective and Balanced Angiotensin II Receptor Antagonists in a Porcine

Coronary Artery Model of Vascular Restenosis, Circulation, 93, 1009 (1996).

93. R. A. Rivero, N. J. Kevin, S. D. Kivlighn, G. J. Zingaro, R. S. Chang and W. J.

Greenlee, L-162,389: A Potent Orally Active Angiotensin II Receptor Antagonist

with Balanced Affinity to Both AT1 and AT2 Receptor Subtypes, Bioorg. Med.

Chem. Letts., 6, 307 (1996).

94. S. E. de Laszlo, T. W. Glinka, W. J. Greenlee, R. Ball, R. B. Nachbar and K.

Prendergast, The Design, Binding Affinity Prediction and Synthesis of

Macrocyclic Angiotensin II AT1 and AT2 Receptor Antagonists, Bioorg. Med.

Chem. Letts., 6, 923 (1996).

95. D. L. Williams, Jr., K. L. Murphy, N. A. Nolan, J. A. O'Brien, E. V. Lis, Jr., D. J.

Pettibone, B. V. Clineschmidt, S. M. Krause, D. F. Veber, E. M. Naylor, P. K.

Chakravarty, T. F. Walsh, D. M. Dhanoa, A. Chen, S. W. Bagley, K. J. Fitch and

W. J. Greenlee, Pharmacology of L-744,453, A Novel Nonpeptidyl Endothelin

Antagonist, Life Sci., 58, 1149 (1996).

96. Signe Perlman, Claudio M. Costa-Neto, Ayumi A. Miyakawa, Hans T. Schambye,

Siv. A. Hjorth, Antonio C. M. Paiva, Ralph A. Rivero, William J. Greenlee and

Thue W. Schwartz, Dual Agonistic and Antagonistic Property of Nonpeptide

Angiotensin AT1 Ligands: Susceptibility to Receptor Mutations, Mol.

Pharmacol., 51:301 (1997).

97. S. E. de Laszlo, E. E. Allen, B. Li, D. Ondeyka, R. Rivero, L. Makowitz, C.

Molineaux, S. J. Siliciano, M. S. Springer, W. J. Greenlee and N. Mantlo, A

Nonpeptide Agonist Ligand of the C5a Receptor: Synthesis, Binding Affinity,

Optimization and Functional Characterization, Bioorg. Med. Chem. Letts., 7,

213 (1997).

98. Stephen M. Krause, Thomas F. Walsh, William J. Greenlee, Robert Ranaei,

David L. Williams, Jr. and Salh D. Kivlighn, Renal Protection by a Dual ETA/ETB

Endothelin Antagonist, L-754,142, after Aortic Cross-Clamping in the Dog, J.

Am. Soc. Nephrol., 8: 1061 (1997).

99. W. J. Greenlee, Hypertension - Treatment by Blockade of the Renin-

Angiotensin System, Proceedings, XIVth International Symposium on Medicinal

Chemistry, F. Awouters, Ed., Eur. J. Med. Chem., 32 (Suppl.), 97S, 1997.

17 17

100. William Greenlee and Manoj Desai, Editorial Overview, Current Opinion in

Drug Discovery and Development, 1, 3 (1998).

101. William J. Greenlee and Major Desai, The Chemistry of Drug Design and Lead

Optimization, Editorial Overview, Current Opinion in Drug Discovery and

Development, 2, 264 (1999).

102. Y. Wang, S. Chackalamannil, Z. Hu, J. W. Clader, W. Greenlee, W. Billard, H.

Binch, III, R. Crosby V. Ruperto, R. A. Duffy, R. McQuade and J. E. Lachowicz,

Design and Synthesis of Piperidine Analogs as Potent and Selective M2

Muscarinic Receptor Antagonists, Bioorg. Med. Chem. Letts., 10, 2247 (2000).

103. William J. Greenlee and Major Desai, The Chemistry of Drug Design and Lead

Optimization, Editorial Overview, Current Opinion in Drug Discovery and

Development, 3, 352 (2000).

104. Yuguang Wang, Samuel Chackalamannil, Wei Chang, William Greenlee, Vilma

Ruperto, Ruth A. Duffy, Robert McQuade and Jean E. Lachowicz, Design and

Synthesis of Ether Analogues as Potent and Selective M2 Muscarinic Receptor

Antagonists, Bioorg. Med. Chem. Letts., 11, 891 (2001).

105. W. R. Huckle, M. D. Drag, W. R. Acker, M. Powers, R. C. McFall, D. J. Holder, T.

F. Walsh, R. S. Schwartz, W. J. Greenlee and R. G. Johnson, Jr., Effects of L-

749,329, and ET(A)/ET(B) endothelin receptor antagonist, in a porcine

coronary artery injury model of vascular restenosis, Circulation, 103, 1899

(2001).

106. W. Greenlee, J. Clader, T. Asbertom, S. McCombie, J. Ford, H. Guzik, J.

Kozlowski, S. Li, C. Liu, D. Lowe, S. Vice, H. Zhao, G. Zhou, W. Billard, H. Binch,

R. Crosby, R. Duffy, J. Lachowicz, V. Coffin, R. Watkins, V. Ruperto, C. Strader, L.

Taylor and K. Cox, Muscarinic Agonists and Antagonists in the Treatment of

Alzheimer’s Disesase, Il Framaco, 56, 247 (2001).

107. Craig D. Boyle, Samuel Chackalamannil, John W. Clader, William J. Greenlee,

Hubert B. Josien, James J. Kaminski, Joseph A. Kozlowski, Stuart W. McCombie,

Dennise V. Nazareno, Jayaram R. Tagat, Yuguang Wang, Guowei Zhou, William

Billard, Herbert Binch III, Gordon Crosby, Mary Cohen-Williams, Vicki L. Coffin,

Kathleen A. Cox, Diane E. Grotz, Ruth A. Duffy, Vilman Ruperto and Jean E.

Lachowicz, Metabolic Stabilization of Benzylidene Ketal M2 Muscarinic

Receptor Antagonists via Halonaphthoic Acid Substitution, Bioorg. Med. Chem.

Letts., 11, 2311 (2001).

108. Anandan Palani, Sherry Shapiro, John W. Clader, William J. Greenlee, Kathleen

Cox, Julie Strizki, Michael Endres and Bahige M. Baroudy, Discovery of 4-[(Z)-(4-

18 18

Bromophenyl)ethoxyimino)methyl]-1’-[2,4-dimethyl-3-pyridinyl)carbonyl]-4’-

methyl-1,4’-bipiperidine N-Oxide (SCH 351125): An Orally Bioavailable Human

CCR5 Antagonist for the Treatment of HIV Infection, J. Med. Chem., 44, 3339

(2001).

109. Julie M. Strizki, Serena Xu, Nicole E. Wagner, Lisa Wojcik, Jia Liu, Yan Hou,

Michael Endres, Anandan Palani, Sherry Shapiro, John W. Clader, William J.

Greenlee, Jayaram R. Tagat, Stuart McCombie, Kathleen Cox, Ahmad B. Fawzi,

Chuan-Chu Chou, Catherine Pugliese-Sivo, Liza Davies, Mary E. Moreno, David

D. Ho, Alexandra Trkola, Cheryl A. Stoddart, John P. Moore, Gregory R. Reyes

and Bahige M. Baroudy, SCH-C (SCH 351125), an orally bioavailable, small

molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of

HIV-1 infection in vitro and in vivo, Proc. Natl. Acad. Sci. USA, 98, 12718 (2001).

110. Yuguang Wang, Samuel Chackalamannil, Zhiyong Hu, Brian A. McKittrick,

William Greenlee, Vilma Ruperto, Ruth A. Duffy and Jean E. Lachowicz, Sulfide

Analogs as Potent and Selective M2 Muscarinic Receptor Antagonists, Bioorg.

Med. Chem. Letts., 12, 1087 (2002).

111. Anandan Palani, Sherry Shapiro, Hubert Josien, Thomas Bara, John W. Clader,

William J. Greenlee, Kathleen Cox, Julie M. Stritzki and Bahige M. Baroudy,

Synthesis, SAR, and Biological Evaluation of Oximino-Piperidino-Piperidine

Amides. 1. Orally Bioavailable CCR5 Receptor Antagonists with Potent Anti-HIV

Activity, J. Med. Chem., 45, 3143 (2002).

112. Yuguang Wang, Samuel Chackalamannil, Zhiyong Hu, William Greenlee, John

Clader, James Kaminski, William Billard, Herbert Binch III, Gordon Crosby,

Vilma Ruperto, Ruth A. Duffy, Jean E. Lachowicz, Mary Cohen-Williams, Vicki L.

Coffin, Kathleen A. Cox and Diane E. Grotz, Improving Oral Efficacy of CNS Drug

Candidates: The Discovery of Highly Orally Efficacious Muscarinic M2 Receptor

Antagonists, J. Med. Chem., 45, 5415 (2002).

113. Yuguang Wang, Samuel Chackalamannil, Zhiyong Hu, Craig D. Boyle, Claire M.

Lankin, Yan Xia, Ruo Xu, Theodros Asberom, Dmitri Pissarnitski, Andrew W.

Stamford, William J. Greenlee, Jeffrey Skell, Stanley Kurowski, Subbarao

Vemulapalli, Jairam Palamandra, Madhu Chintala, Ping Wu, Joyce Myers and

Peng Wang, Design and synthesis of xanthine analogues as potent and

selective PDE5 inhibitors, Bioorg. Med. Chem. Letts., 12, 3149 (2002).

114. Manoj C. Desai and William J. Greenlee, Editorial Overview, Chemical

Genomics, Pharmacogenomics and Pharmacogenetics, Current Opinion in Drug

Discovery and Development, 5, 475 (2002).

19 19

115. Andandan Palani, Sherry Shapiro, John W. Clader, William J. Greenlee, David

Blythin, Kathleen Cox, Nicole E. Wagner, Julie Strizki, Bahige M. Baroudy and

Niya Dan, Biological Evaluation and Interconversion Studies of Rotamers of

SCH 351125, an Orally Bioavailable CCR5 Antagonist, Bioorg. Med. Chem.

Letts., 13, 705 (2003).

116. Andandan Palani, Sherry Shapiro, John W. Clader, William J. Greenlee, Susan

Vice, Stuart McCombie, Kathleen Cox, Julie Strizki and Bahige M. Baroudy,

Oximino-Piperidino-Piperidine-Based CCR5 Antagonists. Part 2: Synthesis, SAR

and Biological Evaluation of Symmetrical Heteroaryl Carboxamides, Bioorg.

Med. Chem. Letts., 13, 709 (2003).

117. Anandan Palani, Sundeep Dugar, John W. Clader, William J. Greenlee, Vilma

Ruperto, Ruth A. Duffy and Jean E. Lachowicz, Isopropyl Amide Derivatives of

Potent and Selective Muscarinic M2 Receptor Antagonists, Bioorg. Med. Chem.

Letts., 14, 1791 (2004).

118. John W. Clader, William Billard, Herbert Binch, III, Lian-Yong Chen, Gordon

Crosby, Jr., Ruth A. Duffy, Jennifer Ford, Joseph A. Kozlowski, Jean E.

Lachowicz, Shengjian Li, Charles Liu, Stuart W. McCombie, Susan Vice, Gowei

Zhou and William J. Greenlee, Muscarinic M2 Antagonists: Anthranilamide

Derivatives With Exceptional Selectivity and In Vivo Activity, Bioorg. Med.

Chem. Letts., 14, 319 (2004).

119. Dmitri Pissarnitski, Theodros Asberom, Craig D. Boyle, Samuel Chackalamannil,

Madhu Chintala, John W. Clader, William J. Greenlee, Yueqing Hu, Stanley

Kurowski, Joyce Myers, Jairam Palamanda, Andrew W. Stamford, Subbaro

Vemulapalli, Yuguang Wang, Peng Wang, Ping Wu, and Ruo Xu, SAR

Development of Polycyclic Guanine Derivatives Targeted to the Discovery of a

Selective PDE5 Inhibitor for Treatment of Erective Dysfunction, Bioorg. Med.

Chem. Letts., 14, 1291 (2004).

120. Manoj C. Desai and William J. Greenlee, Editorial Overview: Transporter

Proteins in Drug Disposition and Uptake, Current Opinion in Drug Design and

Development, 7, 395 (2004).

121. Jing Su, Brian A. McKittrick, Haiqun Tang, Michael Czarniecki, William J.

Greenlee, Brian E. Hawes and Kim O’Neill, Discovery of Melanin-Concentrating

Hormone Receptor R1 Antagonists Using High-Throughput Synthesis, Bioorg.

Med. Chem., 13, 1829 (2005).

122. Wen-Lian Wu, Duane A. Burnett, Richard Spring, William J. Greenlee, Michelle

Smith, Leonard Favreau, Ahmad Fawzi, Hongtao Zhang and Jean E. Lachowicz,

Dopamine D1/D5 Receptor Antagonists with Improved Pharmacokinetics:

20 20

Design, Synthesis, and Biological Evaluationm of Phenol Bioisosteric Analogues

of Benzazepine D1/D5 Antagonists, J. Med. Chem., 48, 680 (2005).

123. Craig D. Boyle, Ruo Xu, Theodros Asberom, Samuel Chackalamannil, John W.

Clader, William J. Greenlee, Henry Guzik, Yuequing Hu, Zhiyong Hu, Claire M.

Lankin, Dmitri Pissarnitski, Andrew W. Stamford, Yuguang Wang, Jeffrey Skell,

Stanley Kurowski, Subbarao Vemulapalli, Jairam Palamanda, Madhu Chintala,

Ping Wu, Joyce Myers and Peng Wang, Optimization of Purine Based

PDE1/PDE5 Inhibitors to a Potent and Selective PDE5 Inhibitor for the

Treatment of Male ED, Bioorg. Med. Chem. Letts., 15, 2365 (2005).

124. Mark D. McBriar, Henry Guzik, Ruo Xu, Jaroslava Paruchova, Shengjian Li,

Anandan Palani, John W. Clader, William J. Greenlee, Brian E. Hawes, Timothy

J. Kowalski, Kim O’Neill, Brian Spar and Blair Weig, Discovery of Urea Melanin

Concentrating Hormone Receptor Antagonists: Orally Efficacious Antiobesity

Therapeutics, J. Med. Chem., 48, 2274 (2005).

125. William J. Greenlee and Manoj C. Desai, Editorial Overview: The Role of

Medicinal Chemists in Drug Discovery, Current Opinion in Drug Design and

Development, 8, 419 (2005).

126. Samuel Chackalamannil, Yan Xia, William J. Greenlee, Martin Clasby, Dario

Doller, Hsingan Tsai, Theodros Asberom, Michael Czarniecki, Ho-Sam Ahn,

George Boykow, Carolyn Foster, Jacqueline Agans Fantuzzi, Matthew Bryant,

Janice Lau, and Madhu Chintala, Discovery of Potent Orally Active Thrombin

Receptor (Protease Activated Receptor 1 Antagonists as Novel Antithrombotic

Agents, J. Med. Chem., 48, 5884 (2005).

127. Anandan Palani, Sherry Shapiro, Mark D. McBriar, John W. Clader, William J.

Greenlee, Brian Spar, Timothy J. Kowalski, Constance Farley, John Cook,

Margaret van Heek, Blair Weig, Kim O’Neill, Michael Graziano and Brian

Hawes, Biaryl Ureas as Potent and Orally Efficacious Melanin Concentrating

Hormone Receptor 1 Antagonists for the Treatment of Obesity, J. Med. Chem.,

48, 4746 (2005).

128. Anandan Palani, Sherry Shapiro, Mark D. McBriar, John W. Clader, William J.

Greenlee, Kim O’Neill and Brian Hawes, Biaryl Diamides as Potent Melanin

Concentrating Hormone Receptor 1, Bioorg. Med. Chem. Letts., 15, 5234

(2005).

129. Ruo Xu, Shengjian Li, Jaroslava Paruchova, Mark D. McBriar, Henry Guzik,

Anandan Palani, John W. Clader, Kathleen Cox, William J. Greenlee, Brian E.

Hawes, Timothy J. Kowalski, Kim O’Neill, Brian D. Spar, Blair Weig and Daniel J.

Weston, Bicyclic[4.1.0]heptanes as phenyl replacements for melanin

21 21

concentrating hormone receptor antagonists, Bioorg. Med. Chem., 14, 3285

(2006).

130. Martin C. Clasby, Samuel Chackalamannil, Michael Czarniecki, Dario Doller,

Keith Eagen, William J. Greenlee, Yan Lin, Hsingan Tsai, Yan Xia, Ho-Sam Ahn,

Jacqueline Agans-Fantuzzi, George Boykow, Matthew Bryant, Madhu Chintala,

Carolyn Foster and Janice Lau, Discovery and Synthesis of a Novel Series of

Quinoline Based Thrombin Receptor (PAR-1) Antagoinsts, Bioorg. Med. Chem.

Letts., 16, 1544-1548 (2006).

131. Wen-Lian Wu, Duane A. Burnett, Mary Ann Caplen,Martin S. Domalski, Chad

Bennett, William J. Greenlee, Brian E. Hawes, Kim O’Neill, Blair Weig, Daniel

Weston, Brian Spar and Timothy Kowalski, Design and Synthesis of Orally

Efficacious Benzimidazoles as Melanin-Concentrating Hormone Receptor 1

Antagonists, Bioorg. Med. Chem. Letts., 16, 3674 (2006).

132. Wen-Lian Wu, Duane A. Burnett, Richard Spring, Li Qiang, Thavalakulamgara K.

Sasikumar, Martin S. Domalski, William J. Greenlee, Kim O’Neill and Brian E.

Hawes, Synthesis and Structure–Activity Relationships of Piperidine-Based

Melanin-Concentrating Hormone Receptor 1 Antagonists, Bioorg. Med. Chem.

Letts., 16, 3668 (2006).

133. Yan Xia, Samuel Chackalamannil, Tze-Ming Chan, Michael Czarniecki, Dario

Doller, Keith Eagen, William J. Greenlee, Hsingan Tsai, Yuguang Wang, Ho-Sam

Ahn, George C. Boykow and Andrew T. McPhail, Himbacine derived thrombin

receptor (PAR-1) antagonists: Structure–activity relationship of the lactone

ring, Bioorg. Med. Chem. Letts., 16, 4969 (2006).

134. Bernard R. Neustadt, Jinsong Hao, Neil Lindo, William J. Greenlee, Andrew W.

Stamford, Ennio Ongini, John Hunter, Angela Monopoli, Rosalia Bertorelli,

Carolyn Foster, Leyla Arik, Jean Lachowicz, Kwokei Ng and Kung-.I Feng, Potent,

Selective and Orally Active Adenosine A2A Receptor Antagonists:

Arylpiperazine Derivatives of Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines,

Bioorg. Med. Chem. Letts., 17, 1376 (2007).

135. T.K. Sasikumar, Li Qiang, Duane A. Burnett, William J. Greenlee, Brian E.

Hawes, Timothy J. Kowalski, Kim O’Neill, Brian D. Spar and Blair Weig, Novel

aminobenzimidazoles as selective MCH-R1 antagonists for the treatment of

metabolic diseases, Bioorg. Med. Chem. Letts., 16, 5427-5431 (2006).

136. T.K. Sasikumar, L. Qiang, W.-L. Wu, D.A. Burnett, W.J. Greenlee, K. O’Neill, B.E.

Hawes, M. van Heek and M. Graziano, Tetrahydroisoquinolines as MCH-R1

antagonists, Bioorg. Med. Chem. Letts., 16, 4917-4921 (2006).

22 22

137. Mark D. McBriar, Henry Guzik, Sherry Shapiro, Jaroslava Paruchova, Ruo Xu,

Anandan Palani, John W. Clader, Kathleen Cox, William J. Greenlee, Brian E.

Hawes, Timothy J. Kowalski, Kim O’Neill, Brian Spar, Blair Weg, Daniel J.

Weston, Constance Farley and John Cook, Discovery of Orally Efficacious

Melanin Concentrating Hormone-1 Receptor Antagonists as Antiobesity

Agents. Synthesis, SAR and Biological Evaluation of Bicyclo[3.1.0]hexyl Ureas,

J. Med. Chem., 49, 2294 (2006).

138. Theodros Asberom, Thomas A. Bara, John W. Clader, William J. Greenlee,

Henry S. Guzik, Hubert B. Josien, Wei Li, Eric M. Parker, Dmitri A. Pissarnitski,

Lixin Song Lili Zhang and Zhiqiang Zhao, Tetrahydroquinoline sulfonamides as

-secretase inhibitors, Bioorg. Med. Chem. Letts., 17, 205 (2007).

139. Theodros Asberom, Zhiqiang Zhao, Thomas A. Bara, John W. Clader, William J.

Greenlee, Lynn A. Hyde, Hubert B. Josien, Wei Li, Andrew T. McPhail, Amin A.

Nomeir, Eric M. Parker, Murali Rajagopalan, Lixin Song, Gwendolyn T. Wong,

-secretase inhibitors

efficacious in a transgenic animal model of alzheimer’s disease, Bioorg. Med.

Chem. Letts., 17, 511 (2007).

140. Dmitri A. Pissarnitski,, Theodros Asberom, Thomas A. Bara, Alex V. Buevich,

John W. Clader, William J. Greenlee, Henry S. Guzik, Hubert B. Josien, Wei Li,

Michael McEwan, Brian A. McKittrick, Terry L. Nechuta, Eric M. Parker,Lisa

Sinning, Elizabeth M. Smith, Lixin Song, Henry A. Vaccaro, Johannes H. Voigt,

Lili Zhang, Qi Zhang and Zhiqiang Zhao, 2,6-Disubstituted N-arylsulfonyl

-secretase inhibitors, Bioorg. Med. Chem. Letts., 17, 57 (2007).

141. Martin C. Clasby, Samuel Chackalmannil, Michael Czarniecki, Dario Doller,

Keith Eagen, William Greenlee, Grace Kao, Yan Lin, Hsingan Tsai, Yan Xia, Ho-

Sam Ahn, Jacqueline Agans-Fantuzzi, George Boykow, Madhu Chintala, Carolyn

Foster, April Smith-Thoran, Kevin Alton3, Matthew Bryant, Yunsheng Hsieh,

Janice Lau, and Jairam Palamanda, Metabolism-based identification of a potent

thrombin receptor antagonist, J. Med. Chem., 50, 129 (2007).

142. Tao Guo, Rachael C. Hunter, Rui Zhang and William J. Greenlee, Microwave

assisted synthesis of isothiazolo-, thiazolo-, imidazo-,and pyrimido-

pyrimidinones as novel MCH1R antagonists, Tetrahedron Letts., 48, 613–615

(2007).

143. Silverman, Lisa S.; Caldwell, John P.; Greenlee, William J.; Kiselgof, Eugenia;

Matasi, Julius J.; Tulshian, Deen B.; Arik, Leyla; Foster, Carolyn; Bertorelli,

Rosalia; Monopoli, Angela; Ongini, Ennio. 3H-[1,2,4]-Triazolo[5,1-i]purin-5-

23 23

amine derivatives as adenosine A2A antagonists, Bioorg. Med. Chem. Letts.,

17, 1659-1662 (2007)

144. Hubert Josien, Thomas Bara, Murali Rajagopalan, Theodros Asberom, John W.

Clader, Leonard Favreau, William J. Greenlee, Lynn A. Hyde, Amin A. Nomeir,

Eric M. Parker, Dmitri A. Pissarnitski, Lixin Song, Gwendolyn T. Wong, Lili

Zhang, Qi Zhang and Zhiqiang Zhao, Small Conformationally Restricted

Piperidine N- -Secretase Inhibitors, Bioorg.

Med. Chem. Letts., 17, 5330 (2007)

145. Martin C. Clasby, Samuel Chackalmannil, Michael Czarniecki, Dario Doller,

Keith Eagen, William Greenlee, Yan Lin, Jayaram R. Tagat, Hsingan Tsai, Yan

Xia, Ho-Sam Ahn, Jacqueline Agans-Fantuzzi, George Boykow, Madhu Chintala,

Yunsheng Hsieh, Janice Lau, and Andrew T. McPhail, Himbacine-Derived

Thrombin Receptor Antagonists: Discovery of a New Tricyclic Core, Bioorg.

Med. Chem. Letts., 17, 3647–3651 (2007).

146. Ginny D. Ho, Ana Bercovici, Deen Tulshian, William J. Greenlee, Ahmad

Fawzi,April Smith Torhan and Hongtao Zhang, Synthesis and structure–activity

relationships of 4-hydroxy-4-phenylpiperidines as nociceptin receptor ligands:

Part 1, Bioorg. Med. Chem. Letts., 17, 3023 (2007).

147. Ginny D. Ho, Ana Bercovici, Deen Tulshian, William J. Greenlee, Ahmad Fawzi,

Xiomara Fernandez, Robbie L. McLeod, April Smith Torhan and Hongtao Zhang,

Synthesis and structure–activity relationships of 4-hydroxy-4-phenylpiperidines

as nociceptin receptor ligands: Part 2, Bioorg. Med. Chem. Letts., 17, 3028

(2007).

148. Jing Su, Brian A. McKittrick, Haiqun Tang, Duane A. Burnett, John W. Clader,

William J. Greenlee, Brian E. Hawes, Kim O_Neill, Brian Spar, Blair Weig,

Timothy Kowalski, Steve Sorota, Cheng Li and Tongtong Liu, SAR study of

bicyclo[4.1.0]heptanes as melanin-concentrating hormone receptor, Bioorg.

Med. Chem., 15, 5369 (2007).

149. Xia, Yan; Chackalamannil, Samuel; Clasby, Martin; Doller, Dario; Eagen, Keith;

Greenlee, William J.; Tsai, Hsingan; Agans-Fantuzzi, Jacqueline; Ahn, Ho-Sam;

Boykow, George C.; Hsieh, Yunsheng; Lunn, Charles A.; Chintala, Madhu.

Himbacine derived thrombin receptor (PAR - 1) antagonists: SAR of the

pyridine ring, Bioorg. Med. Chem. Letts., 17, 4509-4513 (2007).

150. Wen-Lian Wu, Duane A. Burnett, Martin Domalski, William J. Greenlee, Cheng

Li, Rosalia Bertorelli, Silva Fredduzzi, Gianluca Lozza, Alessio Veltri and Angelo

Reggiani, Discovery of Orally Efficacious Tetracyclic Metabotropic Glutamate

24 24

Receptor 1 (mGluR1) Antagonists for the Treatment of Chronic Pain, J. Med.

Chem., 50, 5550 (2007).

151. Mariappan V. Chelliah, Samuel Chackalamannil, Yan Xia, Keith Eagen, Martin C.

Clasby, Xiaobang Gao, William Greenlee, Ho-Sam Ahn, Jacqueline Agans-

Fantuzzi, George Boykow, Yunsheng Hsieh, Matthew Bryant, Jairam

Palamanda, Tze-Ming Chan, David Hesk, and Madhu Chintala, Heterotricyclic

Himbacine Analogs as Potent, Orally Active Thrombin Receptor (Protease

Activated Receptor-1) Antagonists, J. Med. Chem., 50, 5147 -5160, 2007.

152. Hongmei Li, Theodros Asberom, Thomas A. Bara, John W. Clader, William J.

Greenlee, Hubert B. Josien, Mark D. McBriar, Amin Nomeir, Dmitri A.

Pissarnitski, Murali Rajagopalan, Ruo Xu, Zhiqiang Zhao, Lixin Song and Lili

Zhang, Discovery of 2,4,6-trisubstituted N-arylsulfonyl piperidines as γ-

secretase inhibitors, Bioorg. Med. Chem. Letts., 17, 6290-6294 (2007).

153. Guoqing Li, Andrew W. Stamford, Ying Huang, Kuo–Chi Cheng, John Cook,

Constance Farley, Jun Gao, Lorraine Ghibaudi, William J. Greenlee, Mario

Guzzi, Margaret van Heek, Joyce J. Hwa, Joe Kelly, Deborra Mullins, Eric M.

Parker, Sam Wainhaus and Xiaoping Zhang, Discovery of Novel Orally Active

Ureido NPY Y5 Receptor Antagonists, Bioorg. Med. Chem. Letts., 18, 1146

(2008).

154. Mark D. McBriar, John W. Clader, Inhou Chu, Robert A. Del Vecchio, Leonard

Favreau, William J. Greenlee, Lynn A. Hyde, Amin A. Nomeir, Eric M. Parker,

Dmitri A. Pissarnitski, Lixin Song, Lili Zhang and Zhiqiang Zhao, Discovery of

amide and heteroaryl isosteres as carbamate replacements in a series of orally

active γ-secretase inhibitors, Bioorg. Med. Chem. Letts., 18, 215 (2008).

155. Samuel Chackalamannil, Yuguang Wang, William J. Greenlee, Zhiyong Hu, Yan

Xia, Ho-Sam Ahn, George Boykow, Yunsheng Hsieh, Jairam Palamanda,

Jacqueline Agans-Fantuzzi, Stan Kurowski, Michael Graziano, and Madhu

Chintala, Discovery of a Novel, Orally Active Himbacine-Based Thrombin

Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity, J. Med.

Chem., 51, 3061 (2008).

156. Madhu Chintala, Michael P. Graziano, Samuel Chackalamannil, William

Greenlee, Teddy Kosoglou, John Strony, Gail Berman and Enrico Veltri,

Thrombin Receptor Antagonist as a Novel Approach for the Treatment of

Atherothrombosis, Nature Insight, Cardiovascular Disease, Supplement to

Nature, Vol. 451, No. 7181 (2008).

157. Unmesh Shah, Craig D. Boyle, Samuel Chackalamannil, Bernard R. Neustadt,

Neil Lindo, William J. Greenlee, Carolyn Foster, Leyla Arik, Ying Zhai, Kwokei

25 25

Ng, Shiyong Wang, Angela Monopoli, Jean E. Lachowicz, Biaryl and heteroaryl

derivatives of SCH 58261 as potent and selective adenosine A2A receptor

antagonists, Bioorg. Med. Chem. Letts., 18, 4199 (2008).

158. Unmesh Shah, Claire M. Lankin, Craig D. Boyle, Samuel Chackalamannil,

William J. Greenlee, Bernard R. Neustadt, Mary E. Cohen-Williams, Guy A.

Higgins, Kwokei Ng, Geoffrey B. Varty, Hongtao Zhang, Jean E. Lachowicz,

Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261

as adenosine A2A receptor antagonists, Bioorg. Med. Chem. Letts., 18, 4204

(2008).

159. Shu-Wei Yang, Ginny Ho, Deen Tulshian, William J. Greenlee, Xiomara

Fernandez, Robbie L. McLeod, Stephen Eckel and John Anthes, Structure–

activity relationships of 3-substituted N-benzhydryl-nortropane Analogs as

Nociceptin Receptor Ligands for the Treatment of Cough, Bioorg. Med. Chem.

Letts., 18, 6340 (2008).

160. Bernard R. Neustadt, Hong Liu, Jinsong Hao, William J. Greenlee, Andrew W.

Stamford, Carolyn Foster, Leyla Arik, Jean Lachowicz, Hongtao Zhang, Rosalia

Bertorelli, Silva Fredduzzi, Geoffrey Varty, Mary Cohen-Williams, Kwokei Ng,

Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-

c]pyrimidines, Bioorg. Med. Chem. Letts., 19, 967 (2009).

161. Shu-Wei Yang, Ginny Ho, Deen Tulshian, William J. Greenlee, Zheng Tan,

Hongtao Zhang, April Smith-Torhan, Ahmad Fawzi, John Anthes, Sherry Lu,

Geoffrey Varty, Xiomara Fernandez, Robbie L. McLeod, John Hey, Identification

of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor

ligands for the management of cough and anxiety, Bioorg. Med. Chem. Letts.,

19, 2482 (2009).

162. Ginny D. Ho, John Anthes, Ana Bercovici, John P. Caldwell, Kuo-Chi Cheng,

Xiaoming Cui, Ahmad Fawzi, Xiomara Fernandez, William J. Greenlee, John

Hey, Walter Korfmacher, Sherry X. Lu, Robbie L. McLeod, Fay Ng, April Smith

Torhan, Zheng Tan, Deen Tulshian, Geoffrey B. Varty, Xiaoying Xu, Hongtao

Zhang, The discovery of tropane derivatives as nociceptin receptor ligands for

the management of cough and anxiety, Bioorg. Med. Chem. Letts., 19, 2519

(2009).

163. T. K. Sasikumar, Li Qiang, Duane A. Burnett, William J. Greenlee, Cheng Li, Larry

Heimark, Birendra Pramanik, Mariagrazia Grilli, Rosalia Bertorelli, Gianluca

Lozza, Angelo Reggiani, Tricyclic Thienopyridine-

pyrimidones/thienopyrimidine-pyrimidones as Orally Efficacious mGluR1

Antagonists for Neuropathic Pain, Bioorg. Med. Chem. Letts., 19, 3199 (2009).

26 26

164. Santhosh F. Neelamkavil, Craig D. Boyle, Samuel Chackalamannil, William J.

Greenlee, Lili Zhang, and Giuseppe Terracina, The discovery of azepane

sulfonamides as potent 11β-HSD1 inhibitors, Bioorg. Med. Chem. Letts., 19,

4563 (2009).

165. Zhaoning Zhu, Zhong-Yue Sun, Yuanzan Ye, Brian McKittrick, William Greenlee,

Michael Czarniecki, Ahmad Fawzi, Hongtao Zhang and Jean Lachowicz, Design

and Discovery of 1,3-Benzodizepines as Novel Dopamine Antagonists, Bioorg.

Med. Chem. Letts., 19, 5218 (2009).

166. Shu-Wei Yang, Ginny Ho, Deen Tulshian, William J. Greenlee, John Anthes,

Xiomara Fernandez, Robbie L. McLeod, John A. Hey and Xiaoying Xu, Discovery

of Orally Active 3-Pyridinyl-tropane As a Potent Nociceptin Receptor Agonist

for the Management of Cough, J. Med. Chem., 52, 5323 (2009).

167. Hubert Josien, Thomas Bara, Murali Rajagopalan, John W. Clader, William J.

Greenlee, Leonard Favreau, Lynn A. Hyde, Amin A. Nomeir, Eric M. Parker,

Lixin Song, Lili Zhang, Qi Zhang, Novel orally active morpholine N-

arylsulfonamides γ-secretase inhibitors with low CYP 3A4 liability, Bioorg. Med.

Chem. Letts., 19, 6032 (2009).

168. Zhong-Yue Sun, Zhaoning Zhu, Yuanzan Ye, Brian McKittrick, Michael

Czarniecki, William Greenlee, Deborra Mullins, Mario Guzzi, Discovery and SAR

of cyclic isothioureas as novel NPY Y1 receptor antagonists, Bioorg. Med.

Chem. Letts., 19, 6012 (2009).

169. T.K. Sasikumar, Duane A. Burnett, William J. Greenlee, Michelle Smith, Ahmad

Fawzi, Hongtao Zhang, Jean E. Lachowicz, Remote functionalization of SCH

39166: Discovery of potent and selective benzazepine dopamine D1 receptor

antagonists, Bioorg. Med. Chem. Letts., 20, 832 (2010).

170. Li Qiang, T.K. Sasikumar, Duane A. Burnett, Jing Su, Haiqun Tang, Yuanzan Ye,

Robert D. Mazzola Jr., Zhaoning Zhu, Brian A. McKittrick, William J. Greenlee,

Ahmad Fawzi, Michelle Smith, Hongtao Zhang, Jean E. Lachowicz, Discovery of

new SCH 39166 analogs as potent and selective dopamine D1 receptor

antagonists, Bioorg. Med. Chem. Letts., 20, 836 (2010).

171. Ruo Xu, David Cole, Ted Asberom, Tom Bara, Chad Bennett, Duane A. Burnett,

John Clader, Martin Domalski, William Greenlee, Lynn Hyde, Hubert Josien,

Hongmei Li, Mark McBriar, Brian McKittrick, Andrew T. McPhail, Dmitri

Pissarnitski, Li Qiang, Murali Rajagopalan, Thavalakulamgar Sasikumar, Jing Su,

Haiqun Tang, Wen-Lian Wu, Lili Zhang, Zhiqiang Zhao, Design and Synthesis of

Tricyclic Sulfones as -Secretase Inhibitors with Greatly Reduced Notch

Toxicity, Bioorg. Med. Chem. Letts., 20, 2591 (2010).

27 27

172. Jack D. Scott, Sarah W. Li, Hongwu Wang, Yan Xia, Charles L. Jayne, Michael W.

Miller, Ruth A. Duffy, George C. Boykow, Timothy J. Kowalski, Brian D. Spar,

Andrew W. Stamford, Samuel Chackalamannil, Jean E. Lachowicz, William J.

Greenlee, Diaryl piperidines as CB1 receptor antagonists, Bioorg. Med. Chem.

Letts., 20, 1278 (2010).

173. Yu-Sen Wang, Corey Strickland, Johannes H. Voigt, Matthew E. Kennedy, Brian

M. Beyer, Mary M. Senior, Elizabeth M. Smith, Terry L. Nechuta, Vincent S.

Madison, Michael Czarniecki, Brian A. McKittrick, Andrew W. Stamford, Eric M.

Parker, John C. Hunter, William J. Greenlee and Daniel F. Wyss, Application of

Fragment-Based NMR Screening, X-ray Crystallography, Structure-Based

Design, and Focused Chemical Library Design to Identify Novel μM Leads for

the Development of nM BACE-1 (β-Site APP Cleaving Enzyme 1) Inhibitors, J.

Med. Chem., 53, 942 (2010).

174. Zhaoning Zhu, Zhong-Yue Sun, Yuanzan Ye, Johannes Voigt, Corey Strickland,

Elizabeth M. Smith, Jared Cumming, Lingyan Wang, Jesse Wong, Yu-Sen Wang,

Daniel F. Wyss, Xia Chen, Reshma Kuvelkar, Matthew E. Kennedy, Leonard

Favreau, Eric Parker, Brian A. McKittrick, Andrew Stamford, Michael Czarniecki,

William Greenlee and John C. Hunter, Discovery of Cyclic Acylguanidines as

Highly Potent and Selective β-Site Amyloid Cleaving Enzyme (BACE) Inhibitors:

Part I—Inhibitor Design and Validation, J. Med. Chem., 53, 951 (2010).

175. T.K. Sasikumar, Li Qiang, Duane A. Burnett, William J. Greenlee, Cheng Li,

Mariagrazia Grilli, Rosalia Bertorelli, Gianluca Lozza, Angelo Reggiani, A-ring

Modifications on the Triazafluorenone Core Structure and Their mGluR1

Antagonist Properties, Bioorg. Med. Chem. Letts., 20, 2474 (2010).

176. Jared Cumming, Suresh Babu, Ying Huang, Carolyn Carrol, Xia Chen, Leonard

Favreau, William Greenlee, Tao Guo, Matthew Kennedy, Reshma Kuvelkar,

Thuy Le, Guoqing Li, Nansie McHugh, Peter Orth, Lynne Ozgur, Eric Parker, Kurt

Saionz, Andrew Stamford, Corey Strickland, Dawit Tadesse, Johannes Voigt, Lili

Zhang, Qi Zhang, Piperazine sulfonamide BACE1 inhibitors: Design, synthesis,

and in vivo characterization, Bioorg. Med. Chem. Letts., 20, 2837 (2010).

177. T. K. Sasikumar, Duane A. Burnett, Theodros Asberom, Wen-Lian Wu, Chad

Bennett, David Cole, Ruo Xu, William J. Greenlee, John Clader, Lili Zhang, Lynn

Hyde, Tetracyclic sulfones as potent γ-secretase inhibitors: Synthesis and

structure activity relationship studies, Bioorg. Med. Chem. Letts., Bioorg. Med.

Chem. Letts., 20, 3645 (2010).

178. Xianhai Huang,, Robert Aslanian,, Wei Zhou, Xiaohong Zhu, Jun Qin,William

Greenlee, Zhaoning Zhu, Lili Zhang, Lynn Hyde, Inhou Chu, Mary Cohen-

28 28

Williams, and Anandan Palani, The Discovery of Pyridone and Pyridazone

Heterocycles as γ-Secretase Modulators, ACS Med. Chem. Letts., 1, 184 (2010).

179. T. K. Sasikumar, Li Qiang, Duane A. Burnett, David Cole, Ruo Xu, Hongmei Li,

William J. Greenlee, John Clader, Lili Zhang, Lynn Hyde, Tricyclic sulfones as

orally active -secretase inhibitors: Synthesis and structure–activity

relationship studies, Bioorg. Med. Chem. Letts., 20, 3632 (2010).

180. Elizabeth M. Smith, Steve Sorota, Hyunjin M. Kim, Brian A. McKittrick, Terry L.

Nechuta, Chad Bennett, Chad Knutson, Duane A. Burnett, Jane Kieselgof,

Zheng Tan, Diane Rindgen, Terry Bridal, Xiaoping Zhou, Yu-Ping Jia, Zoe Dong,

Debbie Mullins, Xiaoping Zhang, Tony Priestley, Craig C. Correll, Deen Tulshian,

Michael Czarniecki, William J. Greenlee, T-type calcium channel blockers: spiro-

piperidine azetidines and azetidinones-optimization, design and synthesis,

Bioorg. Med. Chem. Letts., 20, 4602 (2010).

181. Yan Xia, Samuel Chackalamannil, William J. Greenlee, Yuguang Wang, Zhiyong

Hu, Yuriko Root, Jesse Wong, Jianshe Kong, Ho-Sam Ahn, George Boykow,

Yunsheng Hsieh, Stan Kurowski and Madhu Chintala, Discovery of a Vorapaxar

Analog with Increased Aqueous Solubility, Bioorg. Med. Chem. Letts., 20, 6676

(2010).

182. Hongmei Li, Ruo Xu, David Cole, John W. Clader, William J. Greenlee, Amin A.

Nomeir, Lixin Song, Lili Zhang, Design, synthesis, and structure–activity

relationship studies of N-arylsulfonyl morpholines as -secretase inhibitors,

Bioorg. Med. Chem. Letts., 20, 6606 (2010).

183. Jun Qin, Pawan Dhondi, Xianhai Huang, Mihirbaran Mandal, Zhiqiang Zhao,

Dmitri Pissarnitski, Wei Zhou, Robert Aslanian, Zhaoning Zhu, William

Greenlee, John Clader, Lili Zhang, Mary Cohen-Williams, Nicholas Jones, Lynn

Hyde, Anandan Palani, Discovery of fused 5,6-bicyclic heterocycles as γ-

secretase modulators, Bioorg. Med. Chem. Letts., 21, 664 (2010).

184. Shu-Wei Yang, Jennifer Smotryski, Julius Matasi, Ginny Ho, Deen Tulshian,

William J. Greenlee, Rossella Brusa, Massimiliano Beltramo, Kathleen Cox,

Structure–activity relationships of 2,4-diphenyl-1H-imidazole analogs as CB2

receptor agonists for the treatment of chronic pain, Bioorg. Med. Chem. Letts.,

21, 182 (2011).

185. Jing Su, Haiqun Tang, Brian A. McKittrick, Ruo Xu, John W. Clader, William J.

Greenlee, Lynn Hyde and Lili Zhang, Synthesis and SAR study of tricyclic

sulfones as -secretase inhibitors: C-6 and C-8 positions, Bioorg. Med. Chem.

Letts., 21, 3447 (2011).

29 29

186. Yan Xia, Samuel Chackalamannil, William J. Greenlee, Charles Jayne, Bernard

Neustadt, Andrew Stamford, Henry Vaccaro, Xiaoying (Lucy) Xu, Hana Baker,

Kim O’Neill, Morgan Woods, Brian Hawes, Tim Kowalski, Discovery of a

nortropanol derivative as a potent and orally active GPR119 agonist for type 2

diabetes, Bioorg. Med. Chem. Letts., 21, 3290 (2011).

187. Julius J. Matasi, Stephanie Brumfield, Deen Tulshian, Michael Czarnecki,

William Greenlee, Charles G. Garlisi, Hongchen Qiu, Kristine Devito, Shu-Cheng

Chen, Youngliang Sun, Rosalia Bertorelli, William Geiss, Van-Duc Le, Gregory S.

Martin, Samuel A. Vellekoop, James Haber and Melissa L. Allard, Synthesis and

SAR development of novel P2X7 receptor antagonists for the treatment of

pain: Part 1, Bioorg. Med. Chem. Letts., 21, 3805 (2011).

188. Jun Qin, Wei Zhou, Xianhai Huang,, Pawan Dhondi, Anandan Palani, Robert

Aslanian, Zhaoning Zhu, William Greenlee, Mary Cohen-Williams, Nicholas

Jones, Lynn Hyde, and Lili Zhang, Discovery of a Potent Pyrazolopyridine Series

of γ-Secretase Modulators, ACS Med. Chem. Letts., 2, 471 (2011).

189. Stephanie Brumfield, Julius J. Matasi, Deen Tulshian, Michael Czarniecki,

William Greenlee, Charles Garlisi, Hongchen Qiu, Kristine Devito, Shu-Cheng

Chen, Yongliang Sun, Rosalia Bertorelli, Justin Ansell, William Geiss, Van-Duc

Le, Gregory S. Martin, Samuel A. Vellekoop, James Haber, Melissa L. Allard,

Synthesis and SAR development of novel P2X7 receptor antagonists for the

treatment of pain: Part 2, Bioorg. Med. Chem. Letts., 21, 7287 (2011).

190. Zhong-Yue Sun, Theodros Asberom, Thomas Bara, Chad Bennett, Duane A.

Burnett, Inhou Chou, John Clader, Mary Cohen-Williams, David Cole, Michael

Czarniecki, James Durkin, Gioconda Gallo, William J Greenlee, Hubert Josien,

Xianhai Huang, Lynn Hyde, Nicholas Jones, Irina Kazakevich, Hongmei Li,

Xiaoxiang Liu, Julie Lee, Malcolm MacCoss, Troy McCracken, Amin Nomeir,

Robert Mazzola, Anandan Palani, Eric M. Parker, Dmitri Pissarnitski, Jun Qin,

Lixin Song, Giuseppe Terracina, Monica Vicarel, Johannes H. Voigt, Ruo Xu, Lili

Zhang, Qi Zhang, Zhiqiang Zhao, Xiaohong Zhu, and Zhaoning Zhu, Cyclic

hydroxyamidines as amide isosteres: Discovery of oxadiazolines and

oxadiazines as potent and highly efficacious -secretase modulators in vivo, J.

Med. Chem., Just Accepted Manuscript • DOI: 10.1021/jm201407j •

Publication Date (Web): 18 Nov 2011.

CHAPTERS AND BOOKS 1. Edgar H. Ulm and William J. Greenlee. Inhibitors of the Renin-Angiotensin

System Enzymes, in "Enzyme Inhibitors as Drugs," M. Sandler and H. J. Smith, eds, Oxford University Press, 1989, Chapter 3.

30 30

2. William J. Greenlee and Ruth R. Wexler. Medicinal Chemistry of Angiotensin II

Antagonists, in "Angiotensin Receptors," Juan M. Saavedra and Pieter B. M. W. M. Timmermans, eds., Plenum, New York, 1994, pp 67-85.

3. Stephen E. de Laszlo and William J. Greenlee. Angiotensin II Receptor

Antagonists: Novel Heterocycles, in Pharmacochemistry Library, H. Timmerman, ed., Volume 21, "Medicinal Chemistry of the Renin-Angiotensin System," R. R. Wexler and P. B. M. W. M. Timmermans, eds., Elsevier, New York, 1994, p. 203.

4. Antihypertensive Drugs, edited by Pieter A. van Zwieten and William J.

Greenlee, Harwood Academic Publishers, Amsterdam, 1997. INVITED LECTURES 1. Total Synthesis of Marasmic Acid, Temple University, October 12, 1980. 2. Total Synthesis of Marasmic Acid, University of Maryland, February 3, 1981. 3. The Synthesis of Unusual Amino Acids as Enzyme Inhibitors, State University of

New York at Stony Brook, April 25, 1985. 4. The Synthesis of Unusual Amino Acids as Enzyme Inhibitors, University of Iowa,

June 7, 1985. 5. Design of Inhibitors of Human Renin, Center for Biotechnology, State

University of New York at Stony Brook, May 3, 1989. 6. Design of Inhibitors of Human Renin, McGill University, November 7, 1990. 7. Design and Synthesis of Orally-Active Nonpeptide Angiotensin II Antagonists,

Gordon Research Conference on Medicinal Chemistry, New London, NH, August 5-9, 1991.

8. Design of Human Renin Inhibitors, DuPont Merck Pharamceutical Company,

May 1, 1992. 9. Design and Synthesis of a New Class of Orally-Active Angiotensin II Antagonists,

Royal Society of Chemistry Fine Chemicals and Medicinals Group, meeting on "Recent Advances in Drugs for the Treatment of Cardiovascular Disease, Glasgow, Scotland, October 14-15, 1992.

10. Design and Synthesis of a AT1-Selective and "Balanced (AT1/AT2) Nonpeptidic

Angiotensin II Antagonists, IBC Conference on New Advances in

31 31

Peptidomimetics & Small Molecule Design for Drug Development, Doubletree Hotel, Philadelphia, PA, March 23-25, 1994.

11. Design and Synthesis of AT1-Selective and Balanced Angiotensin II Antagonists,

West Coast Biotechnology Meeting, San Diego, CA, October 14-17, 1995. 12. Antihypertensives: Recent Advances in Development of Blockers of the Renin-

Angiotensin System, XIVth International Symposium on Medicinal Chemistry, Maastrict, Holland, September 8-12, 1996.

13. Muscarinic Agonists and Antagonists in the Treatment of Alzheimer’s Disease,

XVIth International Symposium on Medicinal Chemistry, Bologna, Italy, September 18-22, 2000.

14. Discovery of Muscarinic M2 Receptor Antagonists for the Treatment of

Alzheimer’s Disease and CCR5 Receptor Antagonists for the Treatment of HIV Infection, University Of Minnesota, Departement of Medicinal Chemistry, April 22, 2003.

15. Design and Synthesis of Thrombin Receptor Antagonists, Alfred Burger Award

Address, 229th

American Chemical Society National Meeting, San Diego, CA, March 13-17th, 2005.

16. Design and Synthesis of Thrombin Receptor Antagonists, State University of

New York at Stony Brook, Department of Chemistry, April 22, 2005. 17. Design and Synthesis of Thrombin Receptor Antagonists, 9

th Beijing Healthcare

Industry Forum, Beijing International Conference Center, Beijing, CHINA, October 20, 2005.

18. Design and Synthesis of Thrombin Receptor Antagonists, Shanghai Institute of Organic Chemistry, Shanghai, CHINA, October 25, 2005.

19. Design and Synthesis of Thrombin Receptor Antagonists, American Chemical

Society Mid-Atlantic Regional Meeting (MARM), Hershey, PA, June 4-7, 2006. 20. Design and Synthesis of Thrombin Receptor Antagonists, 21st Annual William S.

Johnson Symposium, Stanford University, Palo Alto, CA, October 14-15, 2006. 21. Design and Synthesis of Thrombin Receptor Antagonists,.” Neurocrine

Biosciences, San Diego, CA, October 17, 2006. 22. Design and Synthesis of Thrombin Receptor Antagonists, Advances in Chemical

Sciences Symposium - sponsored by NESACS, IUPAC and RSC-US, Royal Sonesta Hotel, Cambridge, MA, March 30, 2007.

32 32

23. Design and Synthesis of Thrombin Receptor Antagonists, Wayne State University, Detroit, MI, April 25, 2007.

24. Design and Synthesis of Thrombin Receptor Antagonists, Zhengzhou

University, Zhengzhou, China, June 30, 2007. 25. Design and Synthesis of Thrombin Receptor Antagonists, SAPA China

Pharmaceutical and Biotechnology Conference, Galaxy Hotel, Shanghai, China, July, 3-5, 2007.

26. Design and Synthesis of Thrombin Receptor Antagonists, WuXi Pharmatech,

Shanghai, China, July 6, 2007 27. Design and Synthesis of Thrombin Receptor Antagonists, Advances in Synthetic

and Medicinal Chemistry (ASMC2007), St. Petersburg, Russia, August 28 – September 2, 2007.

28. Design and Synthesis of Thrombin Receptor Antagonists, Northwestern

University, Evanston, Illinois, October 31, 2007. 29. Design and Synthesis of Thrombin Receptor Antagonists, AMRI Drug Discovery

Symposium, Desmond Hotel, Albany, NY, October 15-16, 2008. 30. Design and Synthesis of Thrombin Receptor Antagonists for the Prevention of

Arterial Thrombosis, Bristol-Myers Squibb Smissman Symposium, 237th American Chemical Society National Meeting, Salt Lake City, UT, March 22-26, 2009.

31. Discovery of Drug Candidates at Schering-Plough: Case Histories from

Cardiovascular and CNS Therapy Areas, ACS ProSpectives Conferences on the Discovery, Development & Production of Pharmaceuticals and Therapeutics, Discovery & Selection of Successful Drug Candidates with special emphasis on Structure-Based Drug Design, The Hyatt Regency, Cambridge, MA, April 26 - 29, 2009.

32. Discovery of Drug Candidates at Schering-Plough: Case Histories from

Cardiovascular and CNS Therapy Areas, Institute of Chemical Biology and Drug Discovery (ICB&DD) Symposium, “Frontiers in Chemical Biology and Drug Discovery,” Stony Brook University, Stony Brook, NY, October 6, 2009.

33. Natural Products as Leads for Small Molecule Drug Discovery: The Discovery of

Thrombin Receptor Antagonists Based on the Natural Product Himbacine, Visions in Chemistry Symposium, The Knud Lind Larsen Program, Danish Academy of Technical Sciences, Copenhagen, Denmark, 29-30 January 2010.

33 33

34. Thrombin Receptor Antagonists for the Prevention of Arterial Thrombosis – Discovery of Vorapaxar, Cecil Pickett Retirement Symposium, Merck Research Laboratories, Kenilworth, NJ, September 30, 2010.

35. Discovery of Drug Candidates for the Treatment of Parkinson’s Disease and

Alzheimer’s Disease, Department Symposium, Stevens Institute, Hoboken, NJ, October 20, 2010.

36. Thrombin Receptor Antagonists for the Prevention of Arterial Thrombosis –

Discovery of Vorapaxar, Rahway Connectivity DPS Symposium, Merck Research Laboratories, Rahway, NJ, October 22, 2010.

37. Discovery of Drug Candidates for the Treatment of Parkinson’s Disease and

Alzheimer’s Disease, Department Symposium, Stony Brook University, Stony Brook, NY, November 29, 2010.

U. S. PATENTS 1. Process for Preparing Amino Acids and Esters, Arthur A. Patchett and William

J. Greenlee, U.S. Patent No. 4,275,220 (June 23, 1981). 2. Process for Preparing Amino Acids and Esters, Arthur A. Patchett and William

J. Greenlee, U.S. Patent No. 4,347,375 (August 31, 1982). 3. Substituted Phosphonamides as Antihypertensives, William J. Greenlee, Elbert

E. Harris, Arthur A. Patchett, and Eugene D. Thorsett, U. S. Patent 4,379,146 (April 5, 1983).

4. Antihypertensive Proline Derivatives, William J. Greenlee, David G. Hangauer,

Jr., and Arthur A. Patchett, U. S. Patent No. 4,402,969 (September 6, 1984). 5. Process for Preparing Carboxyalkyl Dipeptides, William J. Greenlee, U. S.

Patent No. 4,442,030 (April 10, 1984). 6. 3-Hydroxy-3-(1-Aminoethyl)-2-Azetidinones, William J. Greenlee, Arthur A.

Patchett, U. S. Patent No. 4,576,748 (March 18, 1986). 7. Aza Analogs of Aminoacid Derivatives as Antihypertensives, William J.

Greenlee and Eugene D. Thorsett, U. S. Patent No. 4,634,715 (January 6, 1987) 8. Process for Preparing ACHPA, Paul F. Schuda, William J. Greenlee, Prasun K.

Chakravarty and Philip Eskola, U. S. Patent No. 4,788,322 (November 29, 1988).

34 34

9. Renin Inhibitors Containing Phenylalanyl-Histidine Replacements, Arthur A. Patchett, William J. Greenlee, William H. Parsons and Prasun K. Chakravarty, U. S. Patent No. 4,839,357 (June 13, 1989).

10. Carboxylalkyl Urea Compounds and Derivatives Thereof Useful as Angiotensin

Converting Enzyme Inhibitors and as Antihypertensives, William J. Greenlee, David G. Hangauer and Arthur A. Patchett, U. S. Patent No. 4,866,087 (September 12, 1989).

11. Di- or Tripeptide Renin Inibitors Containing Lactam Conformational Restriction

in ACHPA, William J. Greenlee, Daniel F. Veber and Peter D. Williams, U. S. Patent No. 5,006,511 (April 9, 1991).

12. Renin Inhibitors Containing Phenylalanine-Histidine Replacements, Arthur A.

Patchett, William J. Greenlee, William H. Parsons and Parsun K. Chakravarty, U. S. Patent No. 5,037,807 (August 6, 1991).

13. Renin Inhibitors Containing Phenylalanyl-Histidine Replacements, Arthur A.

Patchett, William J. Greenlee and Prasun K. Chakravarty, U. S. Patent No., 5,039,664 (August 13, 1991).

14. Renin-Inhibitory Di-, Tri- and Tetrapeptides, Jan ten Broeke and William J.

Greenlee, U. S. Patent No. 5,049548 (September 17, 1991). 15. Imidazole Angiotensin II Antagonists Incorporating Acidic Functional Groups,

Prasun K. Chakravarty, William J. Greenlee, Elizabeth M. Naylor, Arthur A. Patchett and Thomas F. Walsh, U. S. Patent No. 5,126,342 (June 30, 1992).

16. Substituted Pyrollo-Fused 6-Membered Heterocycles as Angiotensin II

Antagonists, Arthur A. Patchett, Nathan B. Mantlo and William J. Greenlee, U. S. Patent No. 5,124, 335 (June 23, 1992).

17. HIV Reverse Transcriptase, William J. Greenlee and P. C. Srinivasan, U. S.

Patent No. 5,124,327 (June 23, 1992). 18. Substituted Pyrimidinones as Angiotensin II Antagonists, Eric E. Allen, William J.

Greenlee, Prasun K. Chakravarty, Arthur A. Patchett and Thomas F. Walsh, U. S. Patent No. 5,100,897 (March 31, 1992).

19. Substituted Imidazo-Fused 6-Membered Heterocycles as Angiotensin II

Antagonists, Prasun K. Chakravarty, William J. Greenlee, Nathan B. Mantlo, Arthur A. Patchett and Thomas F. Walsh, U. S. Patent No. 5,102,880 (April 7, 1992).

20. Angiotensin II Antagonists Incorporating an Indole or Dihydroindole, Scott

Bagley, William J. Greenlee, Daljit S. Dhanoa and Arthur A. Patchett, U. S. Patent No. 5,151,435 (September 29, 1992).

35 35

21. Oxo-Purines as Angiotensin II Antagonists, Prasun K. Chakravarty, William J.

Greenlee, Nathan B. Mantlo, Arthur A. Patchett and Thomas F. Walsh, U. S. Patent No. 5,157,026 (October 20, 1992).

22. Substituted Quinolines as Angiotensin II Antagonists, William J. Greenlee,

David B. R. Johnston and Malcolm MacCoss, U. S. Patent No. 5,157,040 (October 20, 1992).

23. Substituted 1-(2H)-Isoquinolinones Bearing Acidic Functional Groups as

Angiotensin II Antagonists, Prasun K. Chakravarty, William J. Greenlee, Nathan B. Mantlo, Arthur A. Patchett and Dooseop Kim, U. S. Patent No. 5,162,340 (November 10, 1992).

24. Substituted Imidazo-Fused 5-Membered Ring Heterocycles and Their Use as

Angiotensin II Antagonists, William J. Greenlee, David B. R. Johnston, Malcolm MacCoss, Nathan B. Mantlo, Arthur A. Patchett, Prasun K. Chakravarty and Thomas F. Walsh, U. S. Patent No. 5,164,407 (November 17, 1992).

25. Substituted Pyrimidines, Pyrimidinones and Pyridopyrimidines, Eric E. Allen,

William J. Greenlee, Malcolm MacCoss and Arthur A. Patchett, U. S. Patent No. 5,166,206 (November 24, 1992).

26. Angiotensin II Antagonists Incorporating a Substituted Indole or Dihydroindole,

Scott Bagley, William J. Greenlee, Daljit S. Dhanoa and Arthur A. Patchett, U. S. Patent No. 5,175,164 (December 29, 1992).

27. Triazole Angiotensin II Antagonists Incorporating a Substituted Benzyl Element,

William J. Greenlee, Arthur A. Patchett, David Hangauer, Wallace Ashton, Kenneth J. Fitch, Thomas F. Walsh, Ralph A. Rivero and Daljit S. Dhanoa, U. S. Patent No. 5,177,095 (January 5, 1993).

28. Imidazole Angiotensin II Antagonists Incorporating a Substituted Benzyl

Element, William J. Greenlee, Arthur A. Patchett, David Hangauer, Thomas F. Walsh, Kenneth J. Fitch, Ralph A. Rivero and Daljit S. Dhanoa, U. S. Patent No. 5,183,810 (February 2, 1993).

29. Angiotensin II Antagonists Incorporating a Substituted 1,3-Benzodioxole or 1,3-

Benzodithiole, William J. Greenlee and Ralph A. Rivero, U. S. Patent No. 5,187,159 (February 16, 1993).

30. Cyclic Renin Inhibitors Containing 2-Substituted (3S, 4S)-4-Amino-5-Cyclohexyl-

3-Hydroxy Pentanoic Acid, 2-Substituted (3S,4S)-5-Cyclohexyl-3,4-Dihydroxypentanoic Acid or 2-Substituted (4S,5S)-5-Amino-6-Cyclohexyl-4-Hydroxyhexanoic Acid or its Analogs, William J. Greenlee, Ralph A. Rivero Ann E. Weber, Lihu Yang, U. S. Patent No. 5,194,605 (March 16, 1993).

36 36

31. Imidazole Derivatives Bearing Acidic Functional Groups at the 5-Position, Their Compositions and Methods of Use as Angiotensin II Antagonists, Prasun K. Chakravarty, William J. Greenlee, Arthur A. Patchett, U. S. Patent No. 5,236,928 (August 17, 1993).

32. Substituted Pyrazolopyrimidines as Angiotensin II Antagonists, Eric E. Allen,

William J. Greenlee, Prasun K. Chakravarty, Malcolm MacCoss, Arthur A. Patchett and Thomas F. Walsh, U. S. Patent No. 5,2520,521 (October 5, 1993).

33. Cyclic Renin Inhibitors Containing 3(S)-Amino-4-Cyclohexyl-2(R)-Hydroxy-

Butanoic Acid or 4-Cyclohexyl-(2R, 3S)-Dihydroxybutanoic Acid or Related Analogs, Daljit S. Dhanoa, Arthur A. Patchett, William J. Greenlee, William H. Parsons, Thomas A. Halgren, Ann E. Weber and Lihu Yang, U. S. Patent No. 5,254,682 (October 19, 1993).

34. Substituted Imidazopyridines as Angiotensin II Antagonists, Eric. E. Allen,

William J. Greenlee, Prasun K. Chakravarty, Malcolm MacCoss, Arthur A. Patchett and Thomas F. Walsh, U. S. Patent No. 5,260,285 (November 9, 1993).

35. (Biphenylmethyl)pyrazole Angiotensin II Antagonists, Wallace T. Ashton, Linda

L. Chang, William J. Greenlee and Steven M. Hutchins, U. S. Patent No. 5,262,412 (December 3, 1993).

36. Substituted 1,2,4-Triazoles Bearing Acidic Functional Groups as Angiotensin II

Antagonists, Wallace T. Ashton, Prasun K. Chakravarty, Linda L. Chang, William J. Greenlee, Dooseop Kim, Nathan B. Mantlo and Arthur A. Patchett, U. S. Patent No. 5,281614 (January 25, 1994).

37. N,N-Diacylpiperazines, Wallace T. Ashton, Conrad P. Dorn, William J. Greenlee,

Malcolm MacCoss, Sander G. Mills and Mu-Tsu Wu, U. S. Patent No. 5,292,726 (March 8, 1994).

38. Substituted Carbamoyl and Oxycarbonyl Derivatives of Biphenylmethylamides,

Wallace T. Ashton, Linda L. Chang, William J. Greenlee, Steven M. Hutchins and Ralph A. Rivero, U. S. Patent No. 5,312,820 (May 17, 1994).

39. Substituted Imidazo-Fused 6-Membered Heterocycles as Angiotensin II

Antagonists, Prasun K. Chakravarty, William J. Greenlee, Nathan B. Mantlo, Arthur A. Patchett and Thomas F. Walsh, U. S. Patent No. 5,332,744 (June 26, 1994).

40. Substituted Pyrimidines, Pyrimidinones and Pyridopyrimidines, Eric E. Allen,

William J. Greenlee, Malcolm MacCoss and Arthur A. Patchett, U. S. Patent No. 5,324,729 (June 28, 1994).

41. Six-Membered Ring Fused Imidazoles Substituted with Phenoxyphenylacetic

Acid Derivatives, Prasun K. Chakravarty, Kenneth J. Fitch, Elizabeth M. Naylor,

37 37

James R. Tata, Thomas F. Walsh, David L. Williams and William J. Greenlee, U. S. Patent No. 5,334,598 (August 2, 1994).

42. N,N-Diacylpiperazine Tachykinin Antagonists, Sander G. Mills, Richard J. Budhu,

Conard P. Dorn, William J. Greenlee, Malcolm MacCoss and Mu Tsu Wu, U. S. Patent No. 5,344,830 (September 6, 1994).

43. N,N'-Diacylpiperazines as Angiotensin II Antagonists, William J. Greenlee and

Mu-Tsu Wu, U. S. Patent No. 5,348,955 (September 20, 1994). 44. Disubstituted 6-Aminoquinazolinones, Stephen E. de Laszlo, Thomasz W.

Glinka, William J. Greenlee, Prasun K. Chakravarty and Arthur A. Patchett, U. S. Patent No. 5,385,894 (January 31, 1995).

45. Substituted Imidazo-fused 5-Membered Ring Heterocycles as Angiotensin II

Antagonists, William J. Greenlee, David B. R. Johnston, Malcolm MacCoss, Nathan B. Mantlo, Arthur A. Patchett, Prasun K. Chakravarty and Thomas F. Walsh, U. S. Patent No. 5,389,660 (February 14, 1995).

46. Substituted Triazolinones, Triazolinethiones, and Triazolinimines as

Angiotensin II Antagonists, Wallace T. Ashton, Linda L. Chang, Malcolm MacCoss, Prasun K. Chakravarty, William J. Greenlee, Arthur A. Patchett and Kelly Flanagan, U. S. Patent No. 5,411,980 (May 2, 1995).

47. Heterocyclic Compounds Bearing Acidic Functional Groups as Angiotensin II

Antagonists, Prasun K. Chakravarty, William J. Greenlee, Dooseop Kim, Nathan B. Mantlo, Arthur A. Patchett and Ralph A. Rivero, U. S. Patent No. 5,412,097 (May 2, 1995).

48. Substituted Quinazolinones Bearing Acidic Functional Groups as Angiotensin II

Antagonists, Prasun K. Chakravarty, Stephen de Laszlo, Thomas W. Glinka, William J. Greenlee, Nathan B. Mantlo and Arthur A. Patchett, U. S. Patent No. 5,441,959 (August 15, 1995).

49. Angiotensin II Antagonists Incorporating a Substituted Benzyl Element, William

J. Greenlee, David Hangauer, Arthur A. Patchett, Thomas F. Walsh, Kenneth J. Fitch, Daljit S. Dhanoa and Ralph A. Rivero, U. S. Patent No. 5,449,682 (September 12, 1995).

50. Endothelin Antagonists Bearing 5-Membered Heterocyclic Amides, Wallace T.

Ashton, Linda L. Chage and William J. Greenlee, U. S. Patent No. 5,538,991 (July 23, 1996).

51. Substituted Biphenylmethylimidazopyridines, Ralph A. Rivero, Prasun K.

Chakravarty, William J. Greenlee, Nancy J. Kevin and Nathan B. Mantlo, U. S. Patent No. 5,554,625 (September 10, 1996).

38 38

52. Endothelin Antagonists Bearing Pyridyl Amides, Wallace T. Ashton, Linda L. Chang and William J. Greenlee, U. S. Patent No. 5,559,135 (September 24, 1996).

53. Biphenyl Compounds Useful As Endothelin Antagonists, Scott W. Bagley,

Theodore P. Broten, Prasun K. Chackravarty, Daljit S. Dhanao, Kenneth J. Fitch, William J. Greenlee, Nancy Jo Kevin, Douglas J. Pettibone, Ralph A. Rivero, Thomas F. Walsh, David L. Williams, Jr., Richard B. Toupence and Jay M. Matthews, U. S. Patent No. 5,565,485 (October 15, 1996).

54. Endothelin Antagonists, William J. Greenlee and Thomas F. Walsh, U. S. Patent

No. 5,686,478 (November 11, 1997). 55. Phenoxyphenylacetic Acid Derivatives, Scott W. Bagley, Theodore P. Broten,

Prasun K. Chackravarty, Daljit S. Dhanao, Kenneth J. Fitch, William J. Greenlee, Nancy Jo Kevin, Gerard R. Kieczykowski, Douglas J. Pettibone, James R. Tata, Ralph A. Rivero, Thomas F. Walsh, David L. Williams, Jr., Jay M. Matthews and Richard B. Toupence, U. S. Patent No. 5,668,176 (September 16, 1997).

56. Phenoxyphenylacetic Acid Derivatives, Scott W. Bagley, Theodore P. Broten,

Prasun K. Chackravarty, Daljit S. Dhanao, Kenneth J. Fitch, William J. Greenlee, Nancy Jo Kevin, Douglas J. Pettibone, Ralph A. Rivero, James R. Tata, Thomas F. Walsh and David L. Williams, Jr., U. S. Patent No. 5,767,310 (June 16, 1998).

57. Certain 1-(2-Naphthyl) and 1-(2-azanaphthyl)-4-(1-phenylmethyl)piperazines,

Dopamine Receptor Subtype Selective Ligands, William J. Greenlee, Ashit K. Ganguly and Jan W. F. Wasley, U. S. Patent No. 6,040,448 (March 21, 2000).

58. Certain 1-(2-Naphthyl) and 1-(2-azanaphthyl)-4-(1-phenylmethyl)piperazines,

Dopamine Receptor Subtype Selective Ligands, William J. Greenlee, Ashit K. Ganguly and Jan W. F. Wasley, U. S. Patent No. 6,384,224 (May 7, 2002).

59. Muscarinic Antagonists, Craig D. Boyle, William J. Greenlee and Samuel

Chackalamannil, U.S. Patent No. 6,890,936 (May 10, 2005). 60. Adenosine A2A Receptor Antagonists, Craig D. Boyle, Samuel Chackalamannil,

William J. Greenlee, Unmesh Shah and Yan Xia, U.S. Patent No. 6,916811 (July 12, 2005).

61. Adenosine A2A Receptor Antagonists, Bernard R. Neustadt, Neil Lindo, William

J. Greenlee, Deen Tulshian, Lisa S. Silverman, Yan Xia, Craig D. Boyle and Samuel Chackalamannil, U. S. Patent No. 6,897,216 (May 24, 2005).

62. Adenosine A2A Receptor Antagonists, Craig D. Boyle, Samuel Chackalamannil,

William J. Greenlee, Unmesh G. Shah and Yan Xia, U. S. Patent No. 6,916,811 (July 12, 2005).

39 39

63. Selective D1/D5 Receptor Antagonists for the Treatment of Obesity and CND

Disorders, Wen-Lian Wu, Duane Burnett, William J. Greenlee and Thavalakulamgara K. Sasikumar, U. S. Patent No. 7,211,574 (May 1, 2007).

64. Thrombin Receptor Antagonists, Samuel Chackalamannil, William J. Greenlee,

Yuguang Wang, Wenxue Wu, Enrico P. Veltri and Yan Xia, U.S. Patent No. 7,304,078 (December 4, 2007).

65. Neuropeptide Receptor Modulators, Zhaoning Zhu, Zhong-Yue Sun, Yuanzan

C. Ye, Debbora E. Mullins, Brian McKittrick, Andrew Stamford, William J. Greenlee, U. S. Patent No. 7,459,450 B2 (December 2, 2008)

66. 2-Substituted Benzimidazole Piperidines Analogs as Selective Melanin

Concentrating Hormone Receptor Antagonists For the Treatment of Obesity and Related Disorders, Duane A. Burnett, Wen-Lian Wu, T. K. Sasikumar and William J. Greenlee, U. S. Patent No. 7, 511,146 (March 31, 2009).

67. Heterocyclic Aspartyl Protease Inhibitors, Zhaoning Zhu, Brian McKittrick,

Zhong-Yue Sun, Yuanzan C. Ye, Johannes Voigt, Corey Strickland, Elizabeth M. Smith, Andrew Stamford, William J. Greenlee, Robert Mazzola, John Caldwell, Jared N. Cumming, Lingyan Wang, Yusheng Wu, Ulrich Iserloh, Tao Guo, Thuy X. H. Le, Kurt W. Saionz, Suresh D. Babu, Rachel Hunter, U. S. Patent No. 7,592,348 B2 (September 22, 2009).

68. Pyridothienopyridazinone Derivatives as mGluR1 Antagonists, Chad E. Bennett,

William S. Greenlee, Chad E. Knutson, Duane A. Burnett, US Patent No. 7,687,501 (March 30, 2010).

69. Heterocyclic Aspartyl Protease Inhibitors, Zhaoning Zhu, Brian A. McKittrick,

Zhong-Yue Sun, Yuanzan C. Ye, Johannes H. Voigt, Corey Strickland, Elizabeth M. Smith, Andrew Stamford, Willam J. Greenlee, Robert Mazzola, John Caldwell, Jared N. Cumming, Lingyan Wang, Yusheng Wu, Ulrich Iserloh, Tao Guo, Thuy X. H. Le, Kurt W. Saionz, Suresh D. Babu, Rachael C. Hunter, Michelle L. Morris, Gang Qian, and Dawit Tadesse, US Patent No. 7,700,603 B2 (April 20, 2010).

70. Substituted Piperazines as CB1 Antagonists, Eric J. Gilbert, Michael W. Miller,

Jack D. Scott, Andrew W. Stamford, William J. Greenlee and Jay Weinstein, US Patent No. 7,700,597 B2 (April 20, 2010).

71. Thrombin Receptor Antagonists, Samuel Chackalamannil, Martin C. Clasby,

William J. Greenlee, Yuguang Wang, Yan Xia, Enrico P. Veltri and Mariappan V. Chelliah, US Patent No. 7,713,999 B2 (May 11, 2010).

40 40

72. Heterocyclic Aspartyl Protease Inhibitors, Zhaoning Zhu, Brian McKittrick,

Zhong-Yue Sun, Yuanzan C. Ye, Johannes H. Voigt, Corey O. Strickland, Elizabeth M. Smith, Andrew Stamford, William J. Greenlee, Robert D. Mazzola, John P. Caldwell, Jared N. Cumming, Lingyan Wang, Yusheng Wu, Ulrich Iserloh, Xiaoxiang Liu, Tao Guo, Thu X. E. Le, Kurt W. Saionz, Suresh D. Babu, Rachael C. Hunter, Michelle L. Morris, Huizhong Gu, Gang Qian, Dawit Tadesse, Ying Huang, Guoqing Li, Jianping Pan, Jeffrey A. Misiaszek, Gaifa Lai, Jingqi Duo, Chuangxing Qu and Yuefei Shaom US Patent No. 7,773,609 (July 27, 2010).

73. Aspartyl Protease Inhibitors, Zhaoning Zhu, Brian McKittrick, Andrew Stamford,

William J. Greenlee, Xiaoxiang Liu, Mihirbaran Mandal, Johannes H. Voigt, and Corey O. Strickland, US Patent No. 7,868,000 B2 (January 11, 2011).

74. Aspartyl Protease Inhibitors, Zhaoning Zhu, Brian McKittrick, Zhong-Yue Sun,

Yuanzan C. Ye, Johannes H. Voigt, Corey O. Strickland, Elizabeth M. Smith, Andrew Stamford, William J. Greenlee, Robert D. Mazzola, John P. Caldwell, Jared N. Cumming, Lingyan Wang, Yusheng Wu, Ulrich Iserloh, Tao Guo, Thuy Le, Kurt W. Saionz, Suresh D. Babu, Rachel C. Hunter, Michelle L. Morris, Huizhong Gu, Gang Qian, and Dawit Tadesse, US Patent No. 7,973,067 (July 5, 2011).