Indapamide ppt

8/15/2019 Indapamide ppt

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SAR, MOH, TOXICITY AND SIDE EFFECTOF INDAPAMIDE

Presented by: GUIDED BY :Hipparge Nurpasha Dr. Mrs. Mayura Kale

M Pharm (P’Chem.) II Sem Assistant Professor

Department of Pharm. Chemistry

GOVERNMEN CO!!EGE O" PH#RM#C$

Internal Examiner External Examiner

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INDAPAMIDE:

Indapamide is athiazide-like diuretic[1] drug marketed byServier, generally used in the

treatment ofhypertension, as well as decompensatedheart failure. Combination

preparations withperindopril (an ACE inhibitor antihypertensive) are also available..

a benzamide-sulfonamide-indole. It is called a thiazide-like diuretic but structure is

different enough (lacking the thiazo-ring) so it is not clear that the mechanism is

comparable.3

http://en.wikipedia.org/wiki/Thiazide-like_diuretichttp://en.wikipedia.org/wiki/Indapamide#cite_note-1http://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Servierhttp://en.wikipedia.org/wiki/Hypertensionhttp://en.wikipedia.org/wiki/Heart_failurehttp://en.wikipedia.org/wiki/Perindoprilhttp://en.wikipedia.org/wiki/ACE_inhibitorhttp://en.wikipedia.org/wiki/ACE_inhibitorhttp://en.wikipedia.org/wiki/Perindoprilhttp://en.wikipedia.org/wiki/Heart_failurehttp://en.wikipedia.org/wiki/Hypertensionhttp://en.wikipedia.org/wiki/Servierhttp://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Indapamide#cite_note-1http://en.wikipedia.org/wiki/Thiazide-like_diuretic


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Chemical data

Formula C16H16ClN3O3S

Molecular mass 365.835 g/mol

IUPAC Name

4-chloro-N-(2-methyl-2,3-dihydro-

1H-indol-1-yl)-3-

sulfamoylbenzamide

Description

This compound belongs to

the class of organic

compounds known as

benzenesulfonamides.

These are organic

compounds containing a

sulfonamide group that is

S-linked to a benzene ring.

http://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Chlorinehttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Sulfurhttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Sulfurhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Chlorinehttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Chemical_formula


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Kingdom Organic compounds

Super Class Benzenoids

Class Benzene and substituted derivativ

es

Sub Class Benzenesulfonamides

Direct Parent Benzenesulfonamides

Categories

• Antihypertensive Agents

•

Diuretics•Sodium Chloride Symporter

Inhibitors

http://classyfire.wishartlab.com/tax_nodes/C0000000http://classyfire.wishartlab.com/tax_nodes/C0002448http://classyfire.wishartlab.com/tax_nodes/C0002279http://classyfire.wishartlab.com/tax_nodes/C0002279http://classyfire.wishartlab.com/tax_nodes/C0000031http://classyfire.wishartlab.com/tax_nodes/C0000031http://www.drugbank.ca/mesh/antihypertensive-agentshttp://www.drugbank.ca/mesh/diureticshttp://www.drugbank.ca/mesh/sodium-chloride-symporter-inhibitorshttp://www.drugbank.ca/mesh/sodium-chloride-symporter-inhibitorshttp://www.drugbank.ca/mesh/sodium-chloride-symporter-inhibitorshttp://www.drugbank.ca/mesh/sodium-chloride-symporter-inhibitorshttp://www.drugbank.ca/mesh/sodium-chloride-symporter-inhibitorshttp://www.drugbank.ca/mesh/diureticshttp://www.drugbank.ca/mesh/antihypertensive-agentshttp://classyfire.wishartlab.com/tax_nodes/C0000031http://classyfire.wishartlab.com/tax_nodes/C0000031http://classyfire.wishartlab.com/tax_nodes/C0002279http://classyfire.wishartlab.com/tax_nodes/C0002279http://classyfire.wishartlab.com/tax_nodes/C0002448http://classyfire.wishartlab.com/tax_nodes/C0000000


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Pharmacology

Indication

For the treatment of

hypertension, alone or in

combination with other

antihypertensive drugs, as

well as for the treatment of

salt and fluid retention

associated with congestive

heart failure or edema

from pregnancy

(appropriate only in the

management of edema of

pathologic origin during

pregnancy when clearly


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Pharmacodynamics

Indapamide is an antihypertensive and a

diuretic. It contains both a polar sulfamoyl

chlorobenzamide moiety and a lipid- soluble

methylindoline moiety. Indapamide bears astructural similarity to the triazide diuretics

which are known to decrease vascular smooth

muscle reactivity. However, it differs chemically

from the thiazides in that it does not possess the

thiazide ring system and contains only one

sulfonamide group. Indapamide appears to cause

vasodilation, probably by inhibiting the passage

of calcium and other ions (sodium, potassium)

across membranes. This same effect may cause

hypokalcemia in susceptible individuals.

Indapamide has also been shown to cause uterine

myometrial relaxation in experimental animals.

Overall, indapamide has an extra-renalantihypertensive action resulting in a decrease in


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Mechanism of action

Indapamide blocks the slow

component of delayed rectifier

potassium current (IKs) withoutaltering the rapid component

(IKr) or the inward rectifier

current. Specifically it blocks or

antagonizes the action the

proteins KCNQ1 and KCNE1.Indapamide is also thought to

stimulate the synthesis of the

vasodilatory hypotensive

prostaglandin PGE2.

AbsorptionRapidly absorbed from

gastrointestinal tract.


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SYNTHESIS OF INDAPAMIDE

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G-QSAR:

G0S#R is a %'*el gr'up (+ragme%&) ase 0S#R

me&h' e*el'pe y V!i+e eh%'l'gies P*&. !&.1 ,hihsig%i+ia%&ly e%ha%es apaili&y '+ '%*e%&i'%al 0S#R.Gr'up 'r "ragme%& ase 0S#R is als' -%',% as

G0S#R

G0S#R all',s +le/iili&y &' s&uy *ari'us m'leular+ragme%&s '+ i%&eres& i% rela&i'% &' &he *aria&i'% i%

i'l'gial resp'%se.G0S#R pr'*ies si&e spei+i lues +'r esig%i%g %e,

m'leules a% 2ua%&i&a&i*ely prei&i%g &heir a&i*i&y.Gr'up 'r "ragme%& ase 0S#R is als' -%',% as

G0S#R 10


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JUSTIFICATION

Novelty:

Sy%&hesis '+ &he %'*el 'mp'u%s ha*i%g higher p'&e%y

Vari'us i'l'gial a&i*i&y

Useflness:

herapeu&i a&i*i&y agai%s& *ari'us is'rers li-e Ca%er1

3a&erial i%+e&i'%s1 4lers1Viral i%+e&i'%s e&. 11


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P!AN OF "O#$

!i&era&ure sur*ey

Pla%%i%g +'r sy%&hesis1 P#SS s&uies a% '/ii&y ris-

assessme%& s&uies

Sy%&hesis '+ e%5'&hia5'lyl pyrimii%e

Sy%&hesis '+ eri*a&i*es

Chara&eri5a&i'% y spe&ral a%alysis

Sree%i%g '+ pharma'l'gial a&i*i&y (i%*i*' s&uies)

0S#R a%alysis '+ sree%e 'mp'u%s 12


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!ITE#ATU#E SU#%EY

D'%g H.1 0ua% 3. et.al. sy%&hesi5e 67me&hyl787sus&i&u&e7

91:1;7&ria5'l''ur%al '+ m'leular

s&ru&ure1 :??:@ ;97;A)

Shi*araB H1 Ga5i S1 Pa&il S1 Sur,as S. Sy%&hesis a% i'l'giale*alua&i'% '+ s'me e%5'&hia5'le eri*a&i*es. #sia% >

Researh Chem. :?9?@ 8(:);:97;:A.

P S $aa* e& al 3e%5'&hia5'le Di++ere%& Me&h's '+

Sy%&hesis a% Di*erse 3i'l'gial #&i*i&ies3hara&hi

C'llege '+ Pharmay1 3hara&hi%agara1 Ma%ya1

Kar%a&a-a7 6A9;::1 I%ia.

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CONT&&

Kuer-ar S.V.1Pi%gle M .S et al.; # C'%*e%ie%& sy%&hesis '+

87ya%'7;7imi%'7:7me&hyl&hiy'7;H7pyrimi' e%5'&hia5'le

a% i&s rea&i'% ,i&h sele&e %ulei'philes@ #RKIVOC :??

() 9F?79F.

+

14

Anhy.K2CO3S

N

H8C NH:

SCH8

OO

SCH8 S

N

NH8C SCH8

H

O

O

S

N

N

O

H8C

CN

SCH8


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TO'ICITY #IS$ ASSESSMENT STUDIES(

I& is '%e y Osiris Pr'per&y E/pl'rer a% a&eg'ri5e i% &hree ris- le*els7

9)High ris- aler&

:)Meium ris- aler&

8)!', ris- aler&

)Mu&age%i Meium ris-

)umer'ge%i7 Meium ris-

)Irri&a%&7 Meium ris-

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PASS )P#EDICTION OF ACTI%ITY SPECT#A FO#

SUBSTANCES*

I& helps &' +i% m's& pr'ale %e, leas ,i&h

re2uire a&i*i&y spe&ra am'%g &he sy%&hesi5e

'mp'u%s .

I& helps &' re*eals %e, e++e&s a% meha%isms '+a&i'% +'r &rae rugs.

I& pr'*ies &he asis +'r sele&i'% '+ &he m's&

p'&e%&ial 'mp'u%s +'r high &hr'ughpu& sree%i%g

+r'm &he se& '+ e/is&i%g samples.

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FEASIBI!ITYFollowing sources are feasible for project:

Process Sources AvailableSy%&hesis '+ 'mp'u%s C'%*e%&i'%al appara&us1 Mir',a*e

' +i% +u%&i'%al gr'up IR spe&'me&er

eighi%g '+ pr'u& Ele&'%i ala%e

Dryi%g '+ pr'u& H'& air '*e%

"ree5i%g 'r 'l '%i&i'% "ree5er

Pharma'l'gial sree%i%g Animals (After Approval)

"il&ra&i'% Suction & vacuum pump 17


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P#OB!EM ENCOUNTE#ED AND SO!UTION. P#OB!EM SO!UTION

4%a*ailaili&y '+ +e, imp'r&a%&hemials i% I%s&i&u&i'%

Purhase +r'm mar-e& 'r Gi+&samples

4%a*ailaili&y '+ +e, imp'r&a%&i%s&rume%&s li-e NMR1MS

#%alysis +r'm '&her i%s&i&u&i'%.

Rerys&ali5a&i'%

#ppr'*al +'r a%imale/perime%&a&i'% y i%s&i&u&i'%ala%imal e&his 'mmi&&ee

Prese%&a&i'% '+ researh ,'r-+'r a%imal e/perime%&s i% +r'%& '+#%imal e&his 'mmi&&ee '+ &his

I%s&i&u&i'%

S'l*e%& 'mi%a&i'%

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E'PECTED OUTCOME

19


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#EFE#ENCES

P S $aa* e& al 3e%5'&hia5'le Di++ere%& Me&h's '+Sy%&hesis a% Di*erse 3i'l'gial #&i*i&ies3hara&hi

C'llege '+ Pharmay1 3hara&hi%agara1 Ma%ya1 Kar%a&a-a7

6A9;::1 I%ia.

Shi*araB H1 Ga5i S1 Pa&il S1 Sur,as S. Sy%&hesis

a%i'l'gial e*alua&i'% '+ s'me e%5'&hia5'le

eri*a&i*es. #sia% > Researh Chem. :?9?@ 8(:);:97;:A

20


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CONT(

V'gels &e/&''- '+ pra&ial 'rga%i hemis&ry 6&h ei&i'% y3.S. +ur%iss e& al .

G70S#R '+ N'*el :7J#N#N SON#NE a% R#>ESH N##!E

Depar&me%& '+Pharmaeu&ial Chemis&ry1 G'*er%me%&C'llege '+ Pharmay1Osma%pura1 #ura%gaa1 Maharash&ra1

I%ia.21


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CONT&&

M'rrisi'%1R..13'y1R.N.1LOrga%iChemis&ryL1 Ne,y'r-7Pears'% Eua&i'%1VIEi&i'%1:??816?;76?6.

Gup&a1 R. R1 Kumar1 M.1Gup&a1 V1He&er'yli Chemis&ryL1 9s& e%.1 Spri%ger

pulia&i'%s7Ne, Delhi 99???91INDI#1

*'l.91 :??61;A7;166

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Documents

Indapamide ppt