title: Evolution of anti-HIV drug candidates. Part 1: From alpha-anilinophenylacetamide (alpha-APA) to imidoyl thiourea (ITU).
abstract: Stemming from work on a previous clinical candidate, loviride, and other alpha-APA derivatives, a new series of potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been synthesized. The ITU analogues, which contain a unique diarylated imidoyl thiourea, are very active in inhibiting both wild-type and clinically important mutant strains of HIV-1.
authors.affiliation: Janssen Research Foundation, Welsh and McKean Roads, Spring House, PA 19477, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Ludovici
authors.forename: M J
authors.initials: MJ
authors.lastname: Kukla
authors.forename: P G
authors.initials: PG
authors.lastname: Grous
authors.forename: S
authors.initials: S
authors.lastname: Krishnan
authors.forename: K
authors.initials: K
authors.lastname: Andries
authors.forename: M P
authors.initials: MP
authors.lastname: de Béthune
authors.forename: H
authors.initials: H
authors.lastname: Azijn
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: E
authors.initials: E
authors.lastname: Arnold
authors.forename: P A
authors.initials: PA
authors.lastname: Janssen
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology; D000098:Acetophenones / Q000494:pharmacology; D000814:Aniline Compounds / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects; D007097:Imines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000098:Acetophenones; D000814:Aniline Compounds; D019380:Anti-HIV Agents; D007097:Imines; C442361:N'-(2-((2,6-dichlorophenyl)methyl)-1-iminoethyl)-N''-(4-cyanophenyl)thiourea; C442362:alpha-anilinophenylacetamide; C080073:loviride; D054303:HIV Reverse Transcriptase; D013890:Thiourea