title: Design and synthesis of 1H-pyrazolo[3,4-c]pyridine derivatives as a novel structural class of potent GPR119 agonists.
abstract: Design and synthesis of a novel class of 1H-pyrazolo[3,4-c]pyridine GPR119 receptor agonists are described. Lead compound 4 was identified through the ligand-based drug design approach. Modification of the left-hand aryl group (R(1)) and right-hand piperidine N-capping group (R(2)) led to the identification of compound 24 as a single-digit nanomolar GPR119 agonist.
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuda
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kobashi
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Mikami
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Kawamura
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Shiozawa
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kawabe
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hamada
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.affiliation: Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimoto
authors.affiliation: Research Support, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Miyoshi
authors.affiliation: Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Takayama
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kakinuma
authors.affiliation: Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ohtake
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: C519854:GPR119 protein, human; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled
keywords: G-protein coupled receptor; GPR119 agonist; Pyrazolopyridine; Type 2 diabetes mellitus