Indoles and pyridazino[4,5-b]indoles as nonnucleoside analog inhibitors of HIV-1 reverse transcriptase

被引：29

作者：

Font, M ^{[1
]}

Monge, A ^{[1
]}

Cuartero, A ^{[1
]}

Elorriaga, A ^{[1
]}

MartinezIrujo, JJ ^{[1
]}

Alberdi, E ^{[1
]}

Santiago, E ^{[1
]}

Prieto, I ^{[1
]}

Lasarte, JJ ^{[1
]}

Sarobe, P ^{[1
]}

Borras, F ^{[1
]}

机构：

[1] UNIV NAVARRA,CTR INVEST FARMACOBIOL APLICADA,E-31080 PAMPLONA,SPAIN

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 30卷 / 12期

关键词：

indole; nonnucleoside RT inhibitor; syncytia assay; HIV-1(IIIB) HT4lacZ-1 cells;

D O I：

10.1016/0223-5234(96)88316-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and the study of the activity of new indol-2-carboxamides and pyridazino[4,5-b]indoles as inhibitors of HIV-1 reverse transcriptase (RT) are presented. The activity of the compounds synthesized as inhibitors of different types of HIV-1 RT (wild type enzyme and mutant forms P236L, Y181C and P236L/Y181C) was evaluated. The activity of the most active compounds was investigated in the syncytia reduction in vitro assay, in HIV-1(IIIB)-infected HT4lacZ-1 cells. Their potential cytotoxicity was determined in parallel. Two lead compounds, N-[1-[2-(3-isopropylamino)pyridyl]piperazin]-5,6-methylenedioxy indol-2-carboxamide 7q and N-[1-[2-(3-ethylamino)pyridyl]piperazin] 7s have been identified.

引用

页码：963 / 971

页数：9

共 18 条

[1]

ADRISIANO R, 1957, GAZZ CHIM ITAL, V87, P949

[2]

AGGARWAL BB, 1985, J BIOL CHEM, V260, P2345

[3] NEW GENERAL SYNTHESIS OF AROMATIC NITRILES FROM ALDEHYDES [J].

BLATTER, HM ;

STEVENS, GD ;

LUKASZEWSKI, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1961, 83 (09) :2203-&

[4] DENATURATION REFOLDING OF PURIFIED RECOMBINANT HIV REVERSE-TRANSCRIPTASE YIELDS MONOMERIC ENZYME WITH HIGH ENZYMATIC-ACTIVITY [J].

DEIBEL, MR ;

MCQUADE, TJ ;

BRUNNER, DP ;

TARPLEY, WG .

AIDS RESEARCH AND HUMAN RETROVIRUSES, 1990, 6 (03) :329-340

[5] RESISTANCE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE TO TIBO DERIVATIVES INDUCED BY SITE-DIRECTED MUTAGENESIS [J].

DEVREESE, K ;

DEBYSER, Z ;

VANDAMME, AM ;

PAUWELS, R ;

DESMYTER, J ;

DE CLERCQ, E ;

ANNE, J .

VIROLOGY, 1992, 188 (02) :900-904

[6] U-90152, A POTENT INHIBITOR OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION [J].

DUEWEKE, TJ ;

POPPE, SM ;

ROMERO, DL ;

SWANEY, SM ;

SO, AG ;

DOWNEY, KM ;

ALTHAUS, IW ;

REUSSER, F ;

BUSSO, M ;

RESNICK, L ;

MAYERS, DI ;

LANE, J ;

ARISTOFF, PA ;

THOMAS, RC ;

TARPLEY, WG .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (05) :1127-1131

[7] 5TH MUTATION IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE CONTRIBUTES TO THE DEVELOPMENT OF HIGH-LEVEL RESISTANCE TO ZIDOVUDINE [J].

KELLAM, P ;

BOUCHER, CAB ;

LARDER, BA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (05) :1934-1938

[8] MULTIPLE MUTATIONS IN HIV-1 REVERSE-TRANSCRIPTASE CONFER HIGH-LEVEL RESISTANCE TO ZIDOVUDINE (AZT) [J].

LARDER, BA ;

KEMP, SD .

SCIENCE, 1989, 246 (4934) :1155-1158

[9] NEW 5H-PYRIDAZINO[4,5-B]INDOLE DERIVATIVES - SYNTHESIS AND STUDIES AS INHIBITORS OF BLOOD-PLATELET AGGREGATION AND INOTROPICS [J].

MONGE, A ;

ALDANA, I ;

ALVAREZ, T ;

FONT, M ;

SANTIAGO, E ;

LATRE, JA ;

BERMEJILLO, MJ ;

LOPEZUNZU, MJ ;

FERNANDEZALVAREZ, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (10) :3023-3029

[10] ACTIVATION OF A BETA-GALACTOSIDASE RECOMBINANT PROVIRUS - APPLICATION TO TITRATION OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) AND HIV-INFECTED CELLS [J].

ROCANCOURT, D ;

BONNEROT, C ;

JOUIN, H ;

EMERMAN, M ;

NICOLAS, JF .

JOURNAL OF VIROLOGY, 1990, 64 (06) :2660-2668

← 1 2 →