| cpd |
chemical name |
syn |
comment |
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| 4-amino quinoline |
erythrocytic form of most malarial parasite *inactive #
exoerythrocytic form (liver |
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| 1-chloroquine phosphate |
7-chloro-4[4-(diethylamino)-1-methylbutyl] amino quinoline
phosphate |
|
*no effect on liver form |
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| 2-Amodiaquine HCl |
4-[(7-chloro-4-quinolinyl)amino]-2-[(diethylamino)methyl]-phenol
dihydrochloride dihydrate |
|
*similar to chloroquine *3-4 times as active as
quinine |
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| 3-Sontoquine |
7-chloro-4[4-(diethylamino)-1-methylbutyl]
amino 3-methyl quinoline |
|
similat to chloroquine |
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| 4-hydroxychloroquine sulfate |
2-[[4[7-chloro-4-quinolyl)amino]pentyl]ethylamino]ethanol
sulfate (1:1) |
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*antimalarial + ttt of rheumatoid arthritis |
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| 8-aminoquinolines |
*more toxic *active # exoerythrocytic forms not erythrocytic |
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| 1-pamaquine |
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| 2-primaquine |
8-[(4-amino-1-methylbutyl)-amino]6-methoxyquinoline
phosphate |
2 pathways |
*most active drug :kill exo forms of vivax
,falciparum ,malaria,oval & 2ry exo forms of all except falciparum *no
effect on erythro forms so must be used in combinatn therapy |
|
| 9-Amino
acridines |
|
| Quinacrine HCl |
6-chloro-9-[[4-(diethylamino)-1-methylbutyl]
amino]2-methoxyacridine dihydrochloride |
*same mech of action of quinoline (DNA intercalation ) due to
str similarity *effective on erythrocytic *more toxic & less effective
than chloroquine *used also in giardiasis , amoebiasis ,tap worms |
|
| Guanidine & biduanides |
str similarity to pteridine moity of folic acid |
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| chloroquanide HCl (proguanil HCl) |
1-(p-chlorophenyl)-5-isopropylbiguanide HCl |
*it self >not active w id metab to dihydro-s-triazine w has str similarity to pteridine moiety of folic acid v *its
metabolite is potent DHFR inhibitor *used for both types of
malaria *** SAR : 1-subst
of halogen on para position of phenyl ring > increase activity 2-chlorine in
chloroguanide but bromine
>very active 3-second chlorine added to 3 position >enhance activity but more toxic 4-dichloro cpd is more toxic |
|
| Cycloguanil pamoate |
4,6-diamino-1(p-chlorophenyl) 1,2-dihydro-2,2-dimethyl
s-triazine |
|
*the active metabolite *usu not used itself |
|
| pyrimidine analogues |
act on DHFR similary e pteridine ring of DHFA & directly
resp for redn of DHFA >THFA
*effective on exo (vivax) & erythro forms (falciparum) |
|
| 1-pyrimethamine |
5-(4-chlorophenyl)-6-ethyl-1,2,4-pyrimidinediamine |
********not****** *potent DHFR inhibitor >block syn of THFA w
is ess for purine & pyrimidine syn ,DNA **used in conjugation e
sulfadoxine as antimalaria (w act on DH pteroate synthetase) SAR :1-e withdrawing gp in position 6 is ess for activity 2-p-chloro
phenyl at position 5 >ess for activity 3-if separatn phenyl ring & pyrimidine
ring by C or O > decrease activity *** it is selective parasitic |
|
| 2-Trimethoprim |
2,4-diamino-5-(3,4,5-trimethoxy benzyl) pyrimidine |
syn >not imp |
*used in combinatn e sulfonamides *more selective to bacteria & not
selective to parasite DHFR |
|
| sulfones & sulfonamides |
exhibit prophylactic activity # resistant p.falciparum |
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| Dapsone |
4,4'-sulfonylbis benzene amine |
|
combinatn e pyrimethamine & antimalarial
combinatn for ttt of chloroquine resistant P.falciparum |
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| Quinine (cinchona alkaloids) |
6-methoxycinchonan-9-ol sulfate (not imp) |
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| miscellaneous (( Mefloquine) |
DL-erythro-d-2-piperidyl-2,8-bis(trifluro
methyl)-4-quinoline methanol |
|
*racemic mix DL *very active # erythrocytic
forms of chloroquine resistant malaria (p.falciparum) |
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