title: Discovery of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs.
abstract: High throughput screening using Automated Ligand Identification System (ALIS) resulted in the discovery of a new series of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs. The optimization campaign led to very potent and competitive compound 39 with a Ki value of 1.5 nM. Compound 39 could be a promising lead compound for research to reduce elevated homocysteine levels.
authors.affiliation: Medicinal Chemistry Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan. Electronic address: Nakao.Akira@mc.mt-pharma.co.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakao
authors.affiliation: Pharmacology Research Laboratories I, Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Medicinal Chemistry Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ueno
authors.affiliation: Medicinal Chemistry Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.affiliation: Medicinal Chemistry Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Setsuta
mesh_terms: D000241:Adenosine / Q000737:chemistry; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D015394:Molecular Structure; D009002:Monomethylhydrazine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000588:Amines; D004791:Enzyme Inhibitors; D043383:Adenosylhomocysteinase; D000241:Adenosine; D009002:Monomethylhydrazine
keywords: Competitive; Homocysteine; S-Adenosyl-l-homocysteine hydrolase inhibitors