bms-488043 and indole

bms-488043 has been researched along with indole* in 2 studies

Other Studies

2 other study(ies) available for bms-488043 and indole

Article	Year
Inhibitors of HIV-1 attachment. Part 7: indole-7-carboxamides as potent and orally bioavailable antiviral agents. Bioorganic & medicinal chemistry letters, 2013, Jan-01, Volume: 23, Issue:1 A series of substituted carboxamides at the indole C7 position of the previously described 4-fluoro-substituted indole HIV-1 attachment inhibitor 1 was synthesized and the SAR delineated. Heteroaryl carboxamide inhibitors that exhibited pM potency in the primary cell-based assay against a pseudotype virus expressing a JRFL envelope were identified. The simple methyl amide analog 4 displayed a promising in vitro profile, with its favorable HLM stability and membrane permeability translating into favorable pharmacokinetic properties in preclinical species. Topics: Amides; Animals; Anti-HIV Agents; Biological Availability; Caco-2 Cells; Cell Membrane Permeability; Crystallography, X-Ray; Dogs; Half-Life; Haplorhini; HIV-1; Humans; Indoles; Microsomes, Liver; Molecular Conformation; Rats; Structure-Activity Relationship; Virus Attachment	2013
Heterobiaryl human immunodeficiency virus entry inhibitors. Journal of medicinal chemistry, 2009, Jul-23, Volume: 52, Issue:14 Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC(50) values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of 1 against a panel of clinical viral isolates. Moreover, current structure-activity relationship studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design. Topics: Animals; Anti-HIV Agents; Drug Discovery; HIV; Humans; Indoles; Inhibitory Concentration 50; Piperazines; Structure-Activity Relationship; Virus Internalization; Virus Replication	2009

Article

Year

Inhibitors of HIV-1 attachment. Part 7: indole-7-carboxamides as potent and orally bioavailable antiviral agents.

Bioorganic & medicinal chemistry letters, 2013, Jan-01, Volume: 23, Issue:1

A series of substituted carboxamides at the indole C7 position of the previously described 4-fluoro-substituted indole HIV-1 attachment inhibitor 1 was synthesized and the SAR delineated. Heteroaryl carboxamide inhibitors that exhibited pM potency in the primary cell-based assay against a pseudotype virus expressing a JRFL envelope were identified. The simple methyl amide analog 4 displayed a promising in vitro profile, with its favorable HLM stability and membrane permeability translating into favorable pharmacokinetic properties in preclinical species.

Topics: Amides; Animals; Anti-HIV Agents; Biological Availability; Caco-2 Cells; Cell Membrane Permeability; Crystallography, X-Ray; Dogs; Half-Life; Haplorhini; HIV-1; Humans; Indoles; Microsomes, Liver; Molecular Conformation; Rats; Structure-Activity Relationship; Virus Attachment

2013

Heterobiaryl human immunodeficiency virus entry inhibitors.

Journal of medicinal chemistry, 2009, Jul-23, Volume: 52, Issue:14

Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC(50) values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of 1 against a panel of clinical viral isolates. Moreover, current structure-activity relationship studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design.

Topics: Animals; Anti-HIV Agents; Drug Discovery; HIV; Humans; Indoles; Inhibitory Concentration 50; Piperazines; Structure-Activity Relationship; Virus Internalization; Virus Replication

2009