title: Synthesis of pyrimido[4,5-c]azepine- and pyrimido[4,5-c]oxepine-based γ-secretase modulators.
abstract: This Letter describes an efficient ring-closing metathesis approach to 2-chloro-4-amino-pyrimido[4,5-c]azepines and 2-chloro-4-amino-pyrimido[4,5-c]oxepines. These chlorides were applied to the synthesis of several potent γ-secretase modulators (GSMs).
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States. Electronic address: Yong-Jin.wu@bms.com.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Jeremy H
authors.initials: JH
authors.lastname: Toyn
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Lorin A
authors.initials: LA
authors.lastname: Thompson
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D010082:Oxepins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D010082:Oxepins; D011743:Pyrimidines; D053829:Amyloid Precursor Protein Secretases
keywords: 2-Chloro-pyrimido[4,5-c]azepin-4-amine; 2-Chloro-pyrimido[4,5-c]oxepin-4-amine; Ring-closing metathesis (RCM); γ-Secretase modulator (GSM)