U-1, Medicinal Chemistry-I, Carewell Pharma

Page 1 of 35
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Carewell Pharma - A family of learning
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search CAREWELL PHARMA on Youtube, Watch Free Video lectures
lP
lP
lP
el
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w
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MEDICINAL CHEMISTRY TS
Ca
Ca
UNTT-Ts
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Thoduction to Medicnal Chunlst
lP
lP
lP
History dvelbpmont
el
el
of Mudidnal Cnistry
w
w
Phuysielegieal phuysicodhnicol
re
properties
re
in relahion
Ca
Ca
biological action
Tovizotion - Pantition (oefficien Protein binding
Solubiliu bonding-Chlahm
a
a
-Hyddqn
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Bioisos erism - Optital 4 eomuical Tsomurism
lP
lP
lP
Mlabolism
el
el
Dhwa
w
w
re
re
Ca
Ca
ma
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ma
ar
ar
ar
www.carewellpharma.in (free notes)

Ph
Ph
Ph
visit website to download free pdf notes

Page 2 of 35
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Inbodudim to Mudidnal Chemishy

lP
lP
lP
el
el
w
w
T is a branch of chumlsy, that
re
re
Ca
Ca
intrsaction ofF orqpnic humisy,
biological
phomacoloq4
nd various othr
Spedl speualities.
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t is a disciplina thor endou
ha
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desian dovelopmun and Symthesis ofF
lP
lP
lP
el
el
pharmaceuticol drugs.
w
w
re
involves
ta re
of existing
Ca
Ca
also studying
dnugthelr btologlcal octivit (probehies)

Ond Stwdue Activity Relahionshup
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a
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rm
CSAR. rm
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ha
-MAhaism of atim
lP
lP
lP
el
el
U of drugs
w
Synthusic of
re
re
drugs
Ca
Ca
SAR (STRUCTURE ACTIVITy RELATIONSHIP
CHEMISTRY SEHIND DRUG

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Ph

Page 3 of 35
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HiSTORY AND
lP
lP
lP
DEVELOPMENT of
el
el
MEDICINAL CHEMISTRY
w
re
re
Ca
Ca
Thu
Th Onclent ivilizahons of hl chinea, t
Hiudus, found to b tha ty Uud
a
a
thoapeutic plawls and
rm
rm
rm
Mnual Tor th
ha
ha
ha
teatemt
lP
lP
lP
also chwed CoCa uaves (lonjaiuiug
el
el
w
w
Cocaiu) Cud Usud
re
re
MUSWoms
Ca
Ca
halludnoqus
Soma natual products Us4 in histo
isto
Such Opium Cluchona Bavk.
a
a
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rm
ha
ha
ha
19M
19 cetuuy noum as ag of innovatin
lP
lP
lP
aud chwwishy)
el
el
w
w
re
re
1253 Hunry naed mouphint wt

Ca
Ca
muy! iodida d Make a Mluw Aubs antl

bf qualetna Aalt of Monphlua((modifted).
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ar

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Ph

Page 4 of 35
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Mouphina deuvahve was uboduced as
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lP
lP
Cough Sedhatie in
el
el
1299.
w
Duig
re
re
Ca 1840 firsF vse of Syntuhic
Ca
Oloanic chemicals weuL iwboduced fo
anauthesa duig a oom emoved lik
ubous Oxide, eur and chloroforr
a
a
rm
rm
rm
186-hanbituic aud Sywhuszed as a
ha
ha
ha
ucuful nypwotic.
lP
lP
lP
184S Salicyllc acicl
el
el
f typuod feren
w
w
uboducod
re
re
Ca
Ca
1899- Aspiin Was monkekd as avdipyetic
wiHout Unplasut sida effus .
Aifter 14 30'sduvelopmun of nw
a
a
rm
rm
dug was Spaudad geaty by Combinahnm rm

ha
ha
ha
of mudicina chmithg + xpeimntal

lP
lP
lP
phanmacolo
el
el
w
Discovey dF
re
re
penicillin in
Ca
Ca
is
first futibiohica w an qeatuF
achieve man ( DisoN by Atexandr fumjua)
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ar

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Ph
Ph

Page 5 of 35
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lP
lP
lP
el
el
w
w
re
re
-lquo Ca
tirs drvg fo peam
Ca
CancAr was nuhooun nmustand
as a alkylatug agu
a
a
rm
rm
rm
ha
ha
ha
n the a?oh Certuny, John lougy
lP
lP
lP
el
el
Oud trlich
w
w
Paul (OR up wsh tL
re
re
Ca
Ca
recepto tuouy i maka undusad
tuar dna biud o hecepton
+
a
a
bamd on he chmcal spvctuL
rm
rm
rm
ha
ha
ha
CombositHon.
lP
lP
lP
el
el
w
w
re
re
Ca
Ca
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 6 of 35
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Phusicochumical propeajies inYelotion do Biologicol adion
lP
lP
lP
el
el
n whidn we 2ow Yolu of SomL phycical and
w
poproputes
re
re
chomical
Ca body ui biclogicol
Ca
achim.
Physico+Chtmical Puydal * Chmlcal
O1onizatin
a
a
Solubuli
rm
rm
rm
(3)auriion cofficient
ha
ha
ha
tHydrogun bonding
lP
lP
lP
Botin Bvding
el
el
Chulahim
w
w
re
Sio Sioisoteism
re
Ca
Ca
Cphtal 0vd Gtomuical isomerism
O Tonisahion
tis a phocoAs buy whh on aom/molewles acqvie

a
a
rm
rm
ngaive Or pociive chag by qainlu or lbsing rm

eluctrms. |
ha
ha
ha
T
Thu 1esulig thangd atom/mouuuls (ollLd an ion.
lP
lP
lP
Tomizom
A/A e release e) A* Cahion)
el
el
A
ctabu)
w
Uwioizd (ionizud) eactept A (Anin

re
re
(nm-ion) fomi
Ca
Ca
Na NatC C
(CHh CooH CH c007+H etc- ek

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Ph
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Ph

Page 7 of 35
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ToNIZATION Vnmzed upopilie
lP
lP
lP
TOnj zd- Hydsophullc
el
el
w
w
re
Tutake
re
Dwuing
hould be (UnlbnlzedSalt (rual)
Ca
Ca
Oug
Absophm
- Drug teadhs ind ( blood
a
a
rm
rm
rm
Hydnophlic
ha
ha
ha
Dnq should be (hydnophl
lP
lP
lP
for tuii
el
el
bL (Tonstd
w
MUsF
w
re
re
Ca
Ca
Oisibuhom
Yva rebs jnjd (celA/hissul or
Ck ofahm
upophiuly'c Cpluesphalipiá)
a
a
rm
rm
Dr shovld ba (ipopilic) rm
ha
ha
ha
-for this
lP
lP
lP
MUs MUsF ba (unionjzud

el
el
w
need t0 roSScell-munbrau
re
re
Mads up wn
Ca
Ca
(plospho i pids)
dwa MUS upopulic in

be upophilut nat
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 8 of 35
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Kelaon to iologial achtons
lP
lP
lP
Rolu of ionizahtom in Biological aion(otniuy) in humans (amimals
el
el
play an
w
inmportan role in phamaozinihu.
re
re
Ta move men off drugs tn body
,
Ca
Ca
. Phaymacointiu involves ADME (Abtorptíom distibuhm, mtabolism
and Exurhion).
A Gicod
balan of Ionized- Unlonzed" form 1s better for
phaumacokinic
a
a
rm
rm
rm
Uhionizud form of drvg -
pophidie nau
ha
ha
ha
ovdzd form of dug CHydhopkilic) natue
lP
lP
lP
Tonized form impart q0d waler Colubilutito t drug
el
el
whidh is ecutial food good binding interation of
w
w
drvg wih is receptor.
re
drug to re celA
Ca
Ca
whils uuonizidorm upA fa CroSS
MembranA
Tha drug must b weakly aúdic weaely basic.

T Thu
daqee of dissouatim Cimizohon) Can b Calwlated
a
a
rm
rm
VSiW hendurcon hasdbaldth tquahn. rm

ha
ha
ha
PH=pka+ loq TonlzdJ -fo an auLa

lP
lP
lP
Cunionid]
el
el
pH pka+ loq (Unioni zud

w
ioni zd)
re
re
Ca
Ca
AtcuthHc hase
eg. aud CHCodH (rugaud
ChCooH - Ch cod +H
(Umzed /uon-jamlzd) C Tmiz4
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ar
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ar

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Ph

Page 9 of 35
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Solubulhiiy
lP
lP
lP
Thd
Tha Maximum amount of Solule partida whidh on
el
el
dissolved in pr loom/gm of solvent is callud t
w
ba
dru a
re
re
"sdvbility Ca of given tmperokue
Ca
dissolved
Soluts hCsodulin)
(Solven J
Tt dupends on tunatUk" of solu and solvent as well as

a
a
'pssurt"(Huduophila't f ipophilic.
rm
rm
rm
Heperatue pH
ha
ha
ha
Th aldms 0und Moltculus of al orqani subijanu ak held
lP
lP
lP
toquthu by various Typuy of bornd'(eq tuydiegn bond,
el
el
dipola -dipole, Tonic bomd ek-)
w
w
re
re
Mhod to iprove Solubilty of drugs
Ca
Ca
Aller L sructun of Molwlu
Us oF Co-Solvtnts (€Hhancol, elt--)
Addikim of surfactan
Combxohio.
a
a
Impotmt (Rehationp biclogital ftetin)
rm
rm
dupends
rm
Sioavailielu of Mawly on hir soluodi
ha
ha
ha
drug
in 4 glven Solvent Sycem.
lP
lP
lP
scluion" bufdr it can

el
el
Drug CSoluk) MUS bin

s atiu
w
AnoW
absorbed y biologital membranL and
re
re
solution intrat witm

DrugsMUSt b in
Ca
Ca
receptors.
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Page 10 of 35
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Paatiionm Coctfitient
lP
lP
lP
TF is th vaio of Conwtraion of a compourds
el
el
wo ar equli brium.
w
(druq) in ti phasus
re
re
Solu upophili (ogevc]
Ca
Ca
-Hyd«ophulit. Cuonle
what, = pauitim coefficteuF

ipophilic (oganlt pha]
Co= Conwnratien of dug in
Concovtrohion of drug in hydrophlic Caqutous phase]
a
a
C
rm
rm
rm
Tnpotne (euahn to biologicol actiuuti)
ha
ha
ha
drug absorphon and distvibuitm.
lP
lP
lP
affe c
Combination wih t pka to
qunrally ued in
el
el
Tis
drug in biologitol Sysem
w
w
of
prectct tu aisbibuhm
re
Sin, Bjological MAmbran an ipophilic in natu

re
Ca
Ca
is dire cHy velakd t
So, th ra of dng ransfe
th Lipophilicity of m molecolu
Matun of dug Ha is
Helb' Rn0 t Solubilit (bicovalibin
)D-
Lipophilicfor is
a
a
Hydropulit o
rm
rm
Sepanahion muHhod
rm
hrough
ha
ha
ha
CO miaswld
lP
lP
lP
Value oF
ipophulic
el
el
drug
K>L,thin
w
hydrophulu.
K<, un drvq
re
re
Ca
Ca
Barbipl panhition coefficienr(K) o.*

pauhhion coethcient (k) 48
Phunobarildl
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Page 11 of 35
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Hudroqun Bonding
lP
lP
lP
Tu ydrogn powd is a spcial dipolt- dipolu ineratim
el
el
butueen u hudrogin alom n a polar bond sudh ab
w
re
re
-H H Ond elechonngaHve alom
N-H
Ca
Ca
0, N,F adom.
HhO
O
a
a
O
rm
rm
rm
ha
ha
ha
Jun auy ughly electro nugative aom CfoNJ atta chd wih
lP
lP
lP
aldm, ydoqn batom elkctrm defident cnd
hydrogun than
el
el
a weak attrachn fo bomd wih antother
w
w
tuy make
re
re
electvo ndh Moleculos Qd this is Callecuydioga
Ca
Ca
bondug. aud i is repesLnfed hy dotfd lin
tis of wo typLs!
1) nrMolecular
a
a
11) Tnramoletular
rm
rm
rm
ha
ha
ha
) Tuenmolecular
H-Domding ormud butween two or
lP
lP
lP
whn
MOH mollwlw.
el
el
givts Ossodatfons of molkwles anodoms dimrs,

w
T
re
re
tmurs et. H H H
Ca
Ca
H-0- --H -0--H-0- H N---- H- N

H-N---
H H
H
Cwale CAmmmia)
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Ph
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Ph

Page 12 of 35
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Lnframoleuwlay udrogen bonCu y
lP
lP
lP
Whn H-bonding IS prmd butween tuo atoms wjminn
el
el
Moletuls.
w
(chulahin).
re
re
-thu result in prmatiom
Ca of Ring
Ca
H-baneln4
Saliaylic Aud
a
a
OH
rm
rm
rm
TmportanA-(Relationm to biologial fehon)
ha
ha
ha
lP
lP
lP
phystcal properhe art affcched by hydrognbondv
Many
uling potut,
el
el
Tnhamolewlar H-bonding ainually datka
w
w
billng poit ond Solubili.
re
re
Luermolecwlar H- bondtng qunrally (nceas muling poit,
Ca
Ca
boiling poin and solvhiig.
ijery inuportaut in Chumuny of
uic Codi
tod
InuportanF m drg
dnvg receptor nerachion as wel as thum
a
a
bioloqical actiu
rm
rm
rm
wil also increa th Waltr sdublili
ha
ha
ha
lP
lP
lP
el
el
w
w
re
re
Ca
Ca
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 13 of 35
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otein Gincuug
lP
lP
lP
Tistu procos in whch dvug mollwtes blnd
el
el
t
w
wim pokein fom a Comblex typa Moluwls
re
re
and
Ca u phunoma Rnown as Projthn Bidig
Ca
CProteln clug bindiug).
o OCO
O
O
ret dna
a
a
rm
rm
rm
(omplex
COrugs)
ha
ha
ha
(etein) fom
lP
lP
lP
-fftea t absorphion of dny,wun drug reachs nto
el
el
Sysk mattc irwlahon bind wih tu plasma protein,
w
w
re
re
whith i aleadly Prstar in blood Ond orm a
Ca
Ca
plasma protn dng Complux
-
Soma proteins whioh pSUn in blodd
(Mosty attachuol) win So

)ftlbunin dug also atadud
o-auid glyuprotein blood celu proteln of exbayaswlan
a
a
)upoprotin Hissu, Gu mosHy wh bloo
rm
rm
)Globu lins proteiin

rm
ha
ha
ha
huwo
-whun dg
dng is Combind wih prokeih thuy fom
lP
lP
lP
of (DMpux
el
el
1) Reversibu
w
w
re
re
n) Ireversibu
Ca
Ca
|Reversib In hu, Th dwg bind wih potin wih vezy

weak athrochon forces lka vandar walls fonces aud
hydhdgen bonding, So tHy Can easy clutach
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ar

Ph
Ph
Ph

Page 14 of 35
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ha
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e. dnd uwn hu dnug bind wh vecaptor
ahd arug bicomi
dru
lP
lP
lP
and give s pharmacological acin
,
el
el
n bind wi h photein
w
Irreesibl bla T drug
re
re
wih stTong
Ca bond ika COvalet bond, so y aneasday
Ca
o duachtd.
So, drvg do no butowu fee and doe not biud
wih Hcector aud ot give any phamalbgical achin.
a
a
mpoutaucQ Relaion-to biological adion)
rm
rm
rm
O0O omlpau
ha
ha
ha
+ xballan flud
lP
lP
lP
-Tuaceliln-ftud
Cell (dana4)
el
el
Protein ctachim
Drug ir
w
w
pu dug
re
re
Ca
Ca
of
-sukahm (
Con
a
a
to
neeol
rm
rm
09au dshe
rm
ha
ha
ha
sit oF
lP
lP
lP
oction vetoptor)
el
el
w
w
re
re
iwfluenu tm bioavaikakulil avd distribulim

Ca
Ca
of gchive compomds (dna

oh Combltx 4 pe dhvg] tmm ae inpontau-fo
(omplet phonmalologico actim.
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 15 of 35
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Chlaion
lP
lP
lP
Ts Ja a OnL prm of CDmplaxattm.
el
el
t a typ of onduna Of
w
of jos/moluwles to utal im.
re
re
*SUbstanu covtaining wd c Mo ugands (whdh
Ca
Ca
as lont paiv) (donor) group My ombint wih a
Mua ion COmplex RnowM as hulats
OMd-a process is RnouM a culain
a
a
(ea Etylnidiaman rmujal
rm
rm
rm
EOTA,
COdre atom
ha
ha
ha
lP
lP
lP
HN Nh
el
el
w
w
re
r typ re
Ca
Ca
foum
Tpuan Relation to biologial attonJ
Whn mtals od, mury, ron and Arsunic buil

p in Our boduy,My (on b oxiC, chilahnhenaby
a
a
rm
rm
used Jo a i. rm
,
ha
ha
ha
n
ntus sa* EDTA is ie ctd iud th bloodstream
lP
lP
lP
this biud wi w nmtal f mak a chlakts

el
el
CMd hun emove MuD ual /inurals Om h body.

w
w
re
re
Usd in poisoning
Ca
Ca
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 16 of 35
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rm
rm
ha
ha
ha
lP
lP
lP
el
el
w
w
Bioisostericm
re
re
Ca
Ca
1n mudiinal Chamist Bjolsoshaes 0 group of dhumical
Substitvert which nave similar physical or uical

propuies wih similar biological actiu.
a
a
rm
rm
rm
C1soke Sama e ConfigurahnJ.
ha
ha
ha
e: CO N CO N2 ekt
lP
lP
lP
el
el
fried man proposud of biosolerim "t phunomna
w
w
a defiidion
re
by which COpou ndls USvally fit wi re Sinilar funchlona)

Ca
Ca
group (isostees) ad possas t Same yp OF
Biological achuily
a
a
ReplacoMu a EEA incrtas bioloqical achuity
rm
rm
rm
or SouhimL dicea s blological actriua J
ha
ha
ha
lP
lP
lP
Tupus of Bioisosjerism -
el
el
w
w
re
re
lassical
Ca
Ca
) Non-lassical
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 17 of 35
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D(assial Gioisostes
lP
lP
lP
Th ave Simi lar shape and Covfiqurohin
el
el
w
w
Of aom valenu eluchm saL).
re
re
wun OnL EEK bloisosftts exchang anotur,t give
Ca
Ca
Similar /desied bolbqical uponu
thuy fuuthtr tlasuificd ast

)Monovalen /Uwivalen
a
a
lelt-u attathd
rm
rm
rm
Ont valenuy
,-
ha
ha
ha
-H,-F -Nh r, -L
lP
lP
lP
1) Oivalent/Bivalen
el
el
w
w
-4- -NH -COC4 - ,-CONH
re
re
Ca
Ca
1)Tivalenr
e CH- ,N-
Tehavalun
,
a
a
=N=, =c=
rm
rm
rm
ha
ha
ha
V) King quivalun
lP
lP
lP
el
el
w
w
re
re
Ca
Ca
NH NH
NH NH
Flvorovraci
(Uradl)
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 18 of 35
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Nn-Cassial EibSOS}os
,
lP
lP
lP
no hav Sam Steic or elechron
do
el
el
bnfiquratin (not fit in dufiridhn Buthuy haut San
w
re
re
proprties
Ca du p hu t giv simiksn biologicod
Ca
propurties (aiuity).
e
NH Y
Y( NH
a
a
rm
rm
rm
HO HO
ha
ha
ha
ID proftno Soeol
lP
lP
lP
ugy efective bromdhodilator agvt n cuweral
el
el
auima spute
w
w
re
portont[Relon to Biologlol Ahthin)

re
Ca
Ca
Biolsosprism a broadly usd to pharmacutial sientu
T is Uud hdu toxiCT, dhang bioovaulalby.
n
a
a
dwa deign, purpo of ex chongn9 o blo-
rm
rm
rm
isost o aotn Is
ehan f desied
ha
ha
ha
biblogical or physicol propanie wiHout changa hin stwct

lP
lP
lP
in
Halb in prodvth on
el
el
of dngs ( Safe + mou tkenve).

w
Solved
re
re
Bioisostericm MOy biological problems.-

Ca
Ca
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 19 of 35
a
rm
rm
rm
ha
ha
ha
Optical and Gepmubic (stexachuvusthy
somerismn
lP
lP
lP
Optical isomoism
el
el
>
w
Thos molv, whidh have Samu molecula, strvtun
re
re
formula and also have sOmu propLrtiA Du uy ditftn in
Ca
Ca
Hneir behaviour Lugut
ownds
fhos moletull whlh YOtalt plan polosud ugu (ooL) is
kuown as optical aci ompound.

a
a
chiral
rm
rm
rm
Ty (ontain * (oabon ( fo ditem gep lalm)
ha
ha
ha
CboH
oorl Lactic add
lP
lP
lP
Hd -C-H H-C- (GH0)
el
el
w
w
re
Enanhiomurs Non-supar imposabl miror magA

re
Ca
Ca
DiasttoisOMIK NOn-Supur inpo salels t nn- miiror imaqu
Drvg IsvbstomuL rotaler ugh

clockwise Dexro rotalony +)
optcally active
a
a
rm
rm
futidodeuiA lworoatoy ) rm
ha
ha
ha
RoL In achon
lP
lP
lP
blologitol
Hurt WhuL both f

are enavtiomu
el
el
Variovsthamplu.
w
t) and ( have dfferen biologital attivtie

re
re
-) adrenalin is mon achve than t) adnalina.

Ca
Ca
n So Unanfiomuri whil
of isomurs Is Toxic.
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 20 of 35
a
rm
rm
rm
ha
ha
ha
lP
lP
lP
H
el
el
C0OH-C C-SH CooH-C -SH
w
re
re
H
Ca Nh
Ca
D- Peniillamia - Penlallamjna
"h +wis, D-peniillgmi, is Ustd in ratmunt of

arthriti's whil L-Penicilianint is hignly toxtc
Tu
a
a
is OCCWHd
du chang in stwcm OF
rm
rm
rm
dvgs, Jo
Con nof bind witHh recemors.
ha
ha
ha
i) Gtomebical isomuism8
lP
lP
lP
- AMso known G-ran isomurism
el
el
um2in4 typs
w
w
Thos Molewles whih hae Sam oF
re
re
atom and Cond, bu
Ca
Ca
"ohih have dufteat 8poha arrangumin of t
atoms.
a
a
rm
rm
H rm
Tran
ha
ha
ha
lP
lP
lP
bloloqical achon
Role in
el
el
achuli drugs Moletoll

1F also afteut + bologicol of
w
w
re
re
t is du to dlfferenu in inmer atomic gap b/

Ca
Ca
group Hquired for actiwl

MOR Pokn +nan Cis-isomLr.
diekuyl stilbexhdl
raW
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 21 of 35
a
rm
rm
rm
ha
ha
ha
On is-drvg, has aucitantur atiuit.
lP
lP
lP
Cisplohnn
Transplahin
el
el
w
w
NHh
N NH2
re
re
Ca
Ca
N
(Anicantr adiuili) no anhicanir atiu
ThHe pOin atach mantF wth -t Haptor

a
a
rm
rm
rm
ha
ha
ha
lP
lP
lP
el
el
w
w
re
re
Ca
Ca
Pecopton eecepton
a
a
rm
rm
Dut o ea Changn n shructun

rm
ofF dug .tF
ha
ha
ha
Con no bind witn HCLsto So not qive ay
lP
lP
lP
phoumatological achon or anly Side etfcehs.

el
el
w
ROvgh duaqvamdp to
re
re
duu 0tuhon
Ca
Ca
PeceptoM
Ketepto
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 22 of 35
a
rm
rm
rm
ha
ha
ha
Orvq Metabolism
lP
lP
lP
el
el
-AMSo know as biotvanu fovmatton
w
re
re
Tu Comversim Of dwg from dumi col
Ca
Ca
On
form to anothir.
Conveat ipid solvblu (non-pola)

a
a
rm
rm
rm
dug Waltr solubu (polar) dwg to
ha
ha
ha
avoid Heab Sovptiom n noltubulu ad
lP
lP
lP
hlp in excehion.(Hmot tu dwq frm body).
el
el
w
w
re
re
ophtic Lipid solublu Waka solubll ltg
Ca
Ca
Cupophulic) (inROAL polauily) hydaopluly'e
Achve dnq nahive form of dwg

which gives ( dots no gie any
a
a
rm
rm
phoumacological phama (oloqical

Hsponsn)
rm
ha
ha
ha
Hpms
lP
lP
lP
co Tnachve dw Acive fom

el
el
SOw
w
(pro dwq) egMophine,-

re
re
MouphinL-6-
Ca
Ca
gluuroidi.
(qchive)
Mebolik
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 23 of 35
a
rm
rm
rm
ha
ha
ha
MOsF of t dug ae lip solvble ( Mçophilíc),
lP
lP
lP
Soat Can b exoeltd ouhwovgh
el
el
w
w
mutalolism. Bul SOm dwg am hydrophilc
re
re
et-) les bio-
Ca
Ca
(ey. Stvptomyein, nuostigminl O
tvasfomud and xCced unchangad.
Melnbolukes m dwq wwdh Conve aft

a
a
rm
rm
rm
mabolism.
aane ph exek ay
ha
ha
ha
kidy
lP
lP
lP
Phm-L Mulabolks -A
el
el
Oxidahn
w
w
Hydvolytis
re
re
RLcu ch'o
Ca
Ca
Orvg
-
-TL Mezhboli 8
Phas COugaho)
a
a
rm
rm
ExDekahim tnough
rm
ha
ha
ha
Unin (tidnu) 4 Bil

lP
lP
lP
el
el
Tha primany sati for dwa aoseptieA

w
w
re
re
uabolm is live and ots an

Ca
Ca
kidny, injestinu , Iungs nd plasma.

ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 24 of 35
a
rm
rm
rm
ha
ha
ha
diffecn kinds oF enzymu

lP
lP
lP
System ptun ga-)
el
el
in liv
w
mououu.
re
re
with Cabiotransform drug
Ca
eMzum locatd in Smoom tdoplasmie.
h wlum oF liver also in otur
Organs kidnuy e...
a
a
SUUh lumgs but
rm
rm
rm
in SmaueL COMc.
ha
ha
ha
lP
lP
lP
mosHy biotvafor mabin don by
el
el
mmro somal
w
w
enzymu SUdh as Cytochreme
re
P-yso re
Ca
Ca
OXda , gluwyonmyl raaferau.
)pnaM -L tathon
n tu,tu dwqs Cah b
a
a
rm
rm
metoloelizd by Oxidoim , keduchm,

rm
ha
ha
ha
lP
lP
lP
huyd volysrs and tncen polaity of dwgs

el
el
SO
dwq n eacdy exoek Sm kidmuu
w
w
re
re
thL
Ca
Ca
non-ntmtic kochon
It is a functionalizotin
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 25 of 35
a
rm
rm
rm
ha
ha
ha
formotton) >
biotosfor
Oxidalion (oxidahire
lP
lP
lP
el
el
MOst Common and
TsA
w
re
re
IMportaut
Ca HOchions among Vonjous pho -1
Ca
reoehin
Tha enzum involved in wu Hohion
rosomau Mono oxy9mo in livenL

a
a
rm
rm
rm
ha
ha
ha
Cuto chrom p45D/ CYP) CYP (45)
lP
lP
lP
thu enym Hqud NADPH 4 O.
el
el
w
w
and also Mon- microso ma enzy ms, MMbamIOnD
re
re
Oxidas
Ca
Ca
In t oction aduhon of OXygun/dur
removol of hydragn ak pla

a
a
a) fAromodic ydroxulaJton
rm
rm
rm
ha
ha
ha
lP
lP
lP
(o
el
el
w
w
re
re
Ca
Ca
PhunyToin
Propranobl ec
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 26 of 35
a
rm
rm
rm
ha
ha
ha
Dolkyodhon
lP
lP
lP
el
el
w
w
-Oxygen alm
re
re
H
Ca
Ca
R-0-CH R-OH +
H H
e Phunacetin to Pavacerambl.
a
a
rm
rm
rm
NúOqun aom
ha
ha
ha
lP
lP
lP
CoJ
RNHO +
el
el
w
w
-Amiiphyliw. to Norhiptylina
re
re
Ca
Ca
c)N- OMidarion NH-OHH
NH
a
a
rm
rm
rm
ha
ha
ha
i) Rettochion
Addinon of ydvogan /removal oft onugu
lP
lP
lP
el
el
Dugs Cowalning (orboyl, nuo, and azo

w
w
re
re
group C broanbformtd by ducive

Ca
Ca
proCMU
Sudh reduchon qewoli alconol and
amino moiene in mupbolism.
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 27 of 35
a
rm
rm
rm
ha
ha
ha
a) Nuo edvchon
lP
lP
lP
el
el
RNOa RNH
w
re
re
Chloramphunico)
Ca
Ca
to aryl amtn
mabolik.
b) kuto rcduiom OH
a
a
R--R
rm
rm
rm
R-CH- 2'
ha
ha
ha
ea
lP
lP
lP
Cortisona to Hudo coisoa
el
el
w
w
c)f20 tduthom
re
re
Ca
Ca
N=N-
a
a
rm
rm
rm
ha
ha
ha
lP
lP
lP
NH+ HhN
el
el
w
w
re
re
Prontosil Sulfanilomids
Ca
Ca
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

.
Page 28 of 35
a
rm
rm
rm
ha
ha
ha
in) Hydrolysis
lP
lP
lP
dw
el
el
in H, mutaboli sA with
w
re
re
(ombinng
Ca walen
Ca
Ester or amids Strau .altonol amids-
a
a
rm
rm
rm
CODH (DoH
ha
ha
ha
CTP
lP
lP
lP
yddlusis
el
el
w
w
re
re
Sali cullc
Ca
Ca
cid
faspiin
=
also SOna otheL 2e0rhon
a
a
rm
rm
rm
ha
ha
ha
lP
lP
lP
Caclizaiom diuycuzahon
el
el
w
w
re
re
Ca
Ca
shNtL
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 29 of 35
a
rm
rm
rm
ha
ha
ha
lP
lP
lP
el
el
w
w
(unthHc ation)
re
re
Pha s& - L Hohin
Ca
Ca
aslen hon phan-1 and also
is
Hhoga not exockd attu phau-1 (on exrd
a
a
rm
rm
rm
thvougn pha-I
ha
ha
ha
A1F Involues ConTugctin w
n endognovVS
lP
lP
lP
as qluuronic aud, sufak,
el
el
Svb uncL SUch
w
w
re
glycin. re
Ca
Ca
L Yeouhion al MOR polan., sd dwg an
idylim (bil)
easily excd by t
a
a
rm
rm
GlvCvrMC rm
exCchn
ha
ha
ha
CodH acid
lP
lP
lP
el
el
w
HO
re
re
Satula'c
Ca
Ca
HO
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 30 of 35
a
rm
rm
rm
ha
ha
ha
alvcuvondc gcid
lP
lP
lP
el
el
enzyma Ud
w
gluwrouyltransfesa su.
re
re
Ca UDP
Ca
- OH group CO nTugattd with gluuronic aú4.
a
a
rm
rm
rm
COOH
Uosomad
ha
ha
ha
Cluwrony
lP
lP
lP
Htawy fracu
oH
el
el
w
w
(salityIre
re
aud) HO
re
Ca
Ca
CODH
Dw+UDPG-NOWsUa HO
OH
teid
a
a
Drug
rm
rm
glucuronids rm
ha
ha
ha
+ UDP
lP
lP
lP
el
el
mot dwgs
w
w
re
re
Aspivin, avacetamol, PABA,

Ca
Ca
Morphín ert
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 31 of 35
a
rm
rm
rm
ha
ha
ha
) Sulfat »
lP
lP
lP
Th phunolic Compounds ad
el
el
w
w
sferoida Sulfated Sulfo nnirase
by
re
re
Ca
Ca
C sULT&J
Meyl dopa , chloramphuniaol e.

a
a
1) Glyine Cougotion
rm
rm
rm
whidh Coboxylit add (cooH)
ha
ha
ha
lP
lP
lP
gdup (onJugated with glycina
el
el
w
w
Saljuylaes, nicotinc acd et.
,
re
re
Ca
Ca
V) Azehyloion
Compounds having amino o
udrozina COuugated wlth h

-A
a
a
help f 2ym. fAutyl CGUnzym
rm
rm
rm
ha
ha
ha
Acety
C0-A
lP
lP
lP
R-NH R-NH COCH

el
el
w
eg Suformoamudus Sulfonamjdus , hydalazil,

re
re
PAS elc--
Ca
Ca
othns tothons of phak -T an

My
Soma
,
lahon Glutathon (DwJugannnucdiodi syntuuia
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 32 of 35
a
rm
rm
rm
ha
ha
ha
lP
lP
lP
facor afkctig drug mutatolim includling
el
el
StexoChinial as pec
w
re
re
Ca
Ca
) chtnikal facor
a) EnzymL induchin
b) nzym inhibtin
a
a
rm
rm
rm
n) Bioloqitalfactor
ha
ha
ha
a) Aq
lP
lP
lP
b) Die
el
el
difeen
w
w
c) Sex
re
tu dne re
Ca
Ca
u) Phusicochunial propuics of
v) SteRoumical asprcr
a
a
rm
rm
) chermicol asplers rm
ha
ha
ha
lP
lP
lP
a) Enzyma inducinn-
el
el
Tha phunomua of incseaud

w
w
re
re
drog mtabdiztng aii of enaymus oy

Ca
Ca
Several chugs p chenials knoum as enaym

nduchon aqunts Colled enzum induces.
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 33 of 35
a
rm
rm
rm
ha
ha
ha
is du to
lP
lP
lP
incHaM n both liven siz liven blood
el
el
fHow
w
- inuto spbilty of cytbthrom p-4s0 f1o
re
re
enzymh
Ca
Ca
Orod
CYPA nadte Ellninatd
CDwtraephic
sterod Induction
a
a
rm
rm
rm
Rifampin- enzuym nduurs
ha
ha
ha
lP
lP
lP
el
el
bEnzym inhibthim:
w
w
in t muizbolizlng
A denau dn
re
re
Ca
Ca
an enzumL is Callld ab Unzymt
abulit of
inhi uhn.
diret interadionMa a enuumi cik # Chang
enzymu octiu -(. 4na-(onb
a
a
rm
rm
rm
ndireu
o fall in rai of ezymL
ha
ha
ha
du
syntuis (Hpxssjn). or
lP
lP
lP
el
el
or
du to nubiha duftceincy
w
physioloqy).
harmonal imbalana (alend
re
re
Ca
Ca
Trfenadin CesAActive antihistamind.
rdetien Inhibltian
Futhomycin keto(onazol
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 34 of 35
a
rm
rm
rm
ha
ha
ha
) Bioogical factor
lP
lP
lP
el
el
w
w
a) fhak
re
re
Thu dwa muabolic ra is duffrtnr
Ca
Ca
in differot ag group
nuonatcs (upto monH) - -neofavs (m-1y)

-sloully
a
a
rm
rm
rm
uabelism
ha
ha
ha
devtlopmut of mkosomal enzyma
lP
lP
lP
chldn1 r- 12y)o muhnbelim- Rapid
el
el
w
w
COwond osdt
re
re
Ca
Ca
dduly Pirm muubohym - slouwly
b)
Tu zym Contt ard acti j
altd (afkrrd) b a dieany Cmponut
a
a
rm
rm
rm
pn dse >
ha
ha
ha
lo sbwly mutobolism
lP
lP
lP
hugh protin diet mpid Tmuttbolim

el
el
tavs nceass
w
potein dicr CnzymiL

re
re
yntns.
Ca
Ca
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

Page 35 of 35
a
rm
rm
rm
ha
ha
ha
cSax difeenca
lP
lP
lP
tr also afect dwg muttbolism.
el
el
w
w
muaholizu sl0w in womenn
re
re
Renzodiazapinu than man.
Ca
Ca
mnbolizi apid a in m
than Jomen-
.thee an also SomLfacor whln afft

a
a
rm
rm
rm
muabolt's m SUn as renanty , disa,
ha
ha
ha
hanmond imbalan
lP
lP
lP
el
el
n) Dhysiochinical pro pirdien
w
w
,Anap et.-
re
pka, Solubail, polany, re

s1zA
Ca
Ca
mayb
also offec +u dug mabolism by
witm atv CTs of enzyms
inuadion
a
a
Strochumical aspF dwg mablim
rm
rm
v) rm
ilaus
ha
ha
ha
dso affur dnrg muuplhtm ,

lP
lP
lP
Soma muskolizin Uymi ofttn displaya

el
el
for ona nontiomu of a d

w
pfrenu
re
re
otun. (erantioeucHu). 1*
Ca
Ca
Ove
dus o dilfe in hin ahon
D4) glucou eaily mulabolisd tha L)alucOSI
not uakchisd
ma
ma
ma
ar
ar
ar

Ph
Ph
Ph

U-1, Medicinal Chemistry-I, Carewell Pharma

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Page 1 of 35

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Inbodudim to Mudidnal Chemishy

dnugthelr btologlcal octivit (probehies)

SAR (STRUCTURE ACTIVITy RELATIONSHIP

CHEMISTRY SEHIND DRUG

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1253 Hunry naed mouphint wt

muy! iodida d Make a Mluw Aubs antl

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dug was Spaudad geaty by Combinahnm rm

of mudicina chmithg + xpeimntal

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Physico+Chtmical Puydal * Chmlcal

tis a phocoAs buy whh on aom/molewles acqvie

ngaive Or pociive chag by qainlu or lbsing rm

Uwioizd (ionizud) eactept A (Anin

(CHh CooH CH c007+H etc- ek

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MUs MUsF ba (unionjzud

dwa MUS upopulic in

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Tha drug must b weakly aúdic weaely basic.

VSiW hendurcon hasdbaldth tquahn. rm

PH=pka+ loq TonlzdJ -fo an auLa

pH pka+ loq (Unioni zud

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