128019-80-7Relevant academic research and scientific papers
Inhibitors of HIV protease
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, (2008/06/13)
Compounds of formula (I): STR1 wherein: R1 is hydrogen, alkyl, aralkyl, --CORa, --CORb, --CSRa, --CSRb, --SO2 Rb, --CONHRb, --CSNHRb, --CONRb Rb or --CSNRb Rb ; R2 is hydrogen or alkyl; R3 is hydrogen, alkylidene, substituted alkyl, or Rb ; R4 is optionally substituted alkyl, cycloalkyl, or aryl; R5 is Rb O--, Rb Rb N--, Rb HN--, aralkyloxycarbonyloxy or aralkyloxycarbonylamino, or R5 is --(CH2)p --D--(CH2)r --, where D is a single bond, carbonyl, oxygen, sulfur, --NH--, --(CH2 =CH2)-- or --NHCO--; and p and r are each 0 or an integer from 1 to 5; A is --(CH2)m --B--(CH2)n -- where B is a single bond, carbonyl, oxygen, sulfur, --NH--, --(CH2 =CH2)-- or --NHCO--; and m and n are each 0 or an integer from 1 to 5; Ra is alkoxy, aralkyloxy, aryloxy or alkoxycarbonyl; Rb is optionally substituted alkyl, cycloalkyl, heterocyclic, aryl or arylalkenyl; and pharmaceutically acceptable salts and esters thereof and pro-drugs therefor, have the ability to inhibit the activity of HIV protease and may thus be used for the treatment and prophylaxis of AIDS.
Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA - II. Modification of pyrrolidine ring at P1' proline
Komai, Tomoaki,Higashida, Susumu,Sakurai, Mitsuya,Nitta, Tamayo,Kasuya, Atsushi,Miyamaoto, Shuichi,Yagi, Ryuichi,Ozawa, Yuji,Handa, Hiroshi,Mohri, Hiroshi,Yasuoka, Akira,Oka, Shinichi,Nishigaki, Takashi,Kimura, Satoshi,Shimada, Kaoru,Yabe, Yuichiro
, p. 1365 - 1377 (2007/10/03)
Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a Cl atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed K(i) = 4.5 nM against HIV PR and IC90s 0.58 μM and 0.06 μM in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-Cl atom and fused bicyclic heterocycles may be effective in improving their cellular penetration.
