title: [(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic acid derivatives; HIF prolyl 4-hydroxylase inhibitors as oral erythropoietin secretagogues.
abstract: A new series of PHD (HIF prolyl 4-hydroxylase) inhibitors was designed based on the X-ray co-crystal structure of FG-2216. Using a lead generation process, a series of [(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic acid derivatives was developed as potent PHD2 inhibitors. This class of compounds also showed the ability to stabilize HIF-α, to stimulate EPO secretion in in vitro studies, and to increase hematocrit, red blood cell count, and hemoglobin levels in an animal efficacy study.
authors.affiliation: CrystalGenomics, Inc., 5F, Tower A, Korea Bio Park 694-1, Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Yong Rae
authors.initials: YR
authors.lastname: Hong
authors.forename: Hyun Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Seonggu
authors.initials: S
authors.lastname: Ro
authors.forename: Joong Myung
authors.initials: JM
authors.lastname: Cho
authors.forename: In Su
authors.initials: IS
authors.lastname: Kim
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Jung
mesh_terms: D019342:Acetic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011725:Pyridines; D004921:Erythropoietin; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D019342:Acetic Acid
keywords: Erythropoiesis; HIF-PH (PHD); Inhibitor; Stabilizer