title: Pyridine C-region analogs of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.
abstract: A series of pyridine derivatives in the C-region of N-((6-trifluoromethyl-pyridin-3-yl)methyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. The SAR analysis indicated that 6-difluorochloromethyl pyridine derivatives were the best surrogates of the C-region for previous leads. Among them, compound 31 showed excellent antagonism to capsaicin as well as to multiple hTRPV1 activators. It demonstrated strong analgesic activity in the formalin test in mice with full efficacy and it blocked capsaicin-induced hypothermia in vivo.
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: HyungChul
authors: H
authors: Ryu
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Sejin
authors: S
authors: Seo
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Jee-Young
authors: JY
authors: Lee
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Tae-Hwan
authors: TH
authors: Ha
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Sunho
authors: S
authors: Lee
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Aeran
authors: A
authors: Jung
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Jihyae
authors: J
authors: Ann
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Sung-Eun
authors: SE
authors: Kim
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Suyoung
authors: S
authors: Yoon
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Mannkyu
authors: M
authors: Hong
authors: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors: Peter M
authors: PM
authors: Blumberg
authors: Grunenthal Innovation, Grunenthal GmbH, D-52078 Aachen, Germany.
authors: Robert
authors: R
authors: Frank-Foltyn
authors: Grunenthal Innovation, Grunenthal GmbH, D-52078 Aachen, Germany.
authors: Gregor
authors: G
authors: Bahrenberg
authors: Grunenthal Innovation, Grunenthal GmbH, D-52078 Aachen, Germany.
authors: Klaus
authors: K
authors: Schiene
authors: Grunenthal Innovation, Grunenthal GmbH, D-52078 Aachen, Germany.
authors: Hannelore
authors: H
authors: Stockhausen
authors: Grunenthal Innovation, Grunenthal GmbH, D-52078 Aachen, Germany.
authors: Thomas
authors: T
authors: Christoph
authors: Grunenthal Innovation, Grunenthal GmbH, D-52078 Aachen, Germany.
authors: Sven
authors: S
authors: Frormann
authors: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: jeewoo@snu.ac.kr.
authors: Jeewoo
authors: J
authors: Lee
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D044482:Benzeneacetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D044482:Benzeneacetamides; D011725:Pyridines; D013449:Sulfonamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human
keywords: Analgesic; TRPV1 antagonists; Vanilloid receptor 1