title: Synthesis and evaluation of C2-carbon-linked heterocyclic-5-hydroxy-6-oxo-dihydropyrimidine-4-carboxamides as HIV-1 integrase inhibitors.
abstract: Integration of viral DNA into the host cell genome is an obligatory process for successful replication of HIV-1. Integrase catalyzes the insertion of viral DNA into the target DNA and is a validated target for drug discovery. Herein, we report the synthesis, antiviral activity and pharmacokinetic profiles of several C2-carbon-linked heterocyclic pyrimidinone-4-carboxamides that inhibit the strand transfer step of the integration process.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: b.narasimhulunaidu@bms.com.
authors.forename: B Narasimhulu
authors.initials: BN
authors.lastname: Naidu
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Sorenson
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Patel
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Banville
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Beaulieu
authors.affiliation: Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Sagarika
authors.initials: S
authors.lastname: Bollini
authors.affiliation: Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Ira B
authors.initials: IB
authors.lastname: Dicker
authors.affiliation: Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Higley
authors.affiliation: Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Pajor
authors.affiliation: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Dawn D
authors.initials: DD
authors.lastname: Parker
authors.affiliation: Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Terry
authors.affiliation: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Alain
authors.initials: A
authors.lastname: Martel
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
authors.affiliation: Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Krystal
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Walker
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006207:Half-Life; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D019428:HIV Integrase Inhibitors; D006571:Heterocyclic Compounds; D011743:Pyrimidines; D019427:HIV Integrase; C030986:pyrimidine; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: HIV-1; Inhibitor; Integrase; Pyrimidine-4-carboxamide; Strand transfer