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1, 2013 / IV ()
::. - . 3285 . 3286
1. -....................................................................12. ............................................2 2.1....................................................................2 2.2....................................................................4 2.3....................................................................53. ...........................................94. ........................................11
2
1.
, . , , , . , . . , . , , . . , . . 3 () :
1. 2. 3.
, , .
2.
, , : -1 -2 HIV
2.1. -1
, (MetAP). MetAP . : MetAP-1 MetAP-2. MetAP-1 ( )1 , in vivo. MetAP-2, , . MetAP-1 MetAP-2 , . MetAP-1 , MetAP-1 , . MetAP-1 (3R)--(2S)- (2S,3R AHHpA) ( 1) .
1. (3R)--(2)- (Medicinal chemistry into the millennium 2001)
2S-, 3R- , , (AP). MetAP-1 N- , 2S-, 3R- . MetAP-1, ( 2-4) . 2S-, 3R- , - Sharpless ()( Karl Barry Sharpless)2. ( 2-4) MetAP-1 Ki=5-7M ( )3. MetAP-1 Matthews Lowther, .
2.-4. MetAP-1(Medicinal chemistry into the millennium 2001)
2.2. HIV
, , . , , . , HIV-1 Ascidian Didemnum sp. , , . HIV-1 IC50=2 (IC50 e - )4, . HIV . ( 5) .
5. (Medicinal chemistry into the millennium 2001) HIV , , Zhang et al, HIV . HIV-1 . 5 HIV-1 . HIV-1 , HIV . HIV-1 PR , HIV-1 . , .
2.3.
( 2-4 5) ; 2-4 5 . per se ( ) ; , . , , . (-1 ) , HIV , . , , . "", . -3 . , "" . , . . , . Bohacek McMartin, GrowMol . GrowMol -3 . 66702 ( 6) , GrowMol 20000-50000 , , , 200-400 . . , - .
6. 66702(Medicinal chemistry into the millennium 2001)
GrowMol . , - ( 8 a-d). GrowMol P1 P3 , "" 8 8c .
8 a-d. - (Medicinal chemistry into the millennium 2001)
8c GrowMol ( 1).
1. 8 (Medicinal chemistry into the millennium 2001) . 8c , Rhizopus . . GrowMol P1 P2 . , . . P' , (Ki