Title:
【発明の名称】チオール誘導体、メタロ-β-ラクタマーゼ阻害剤
Document Type and Number:
Japanese Patent JP2003521476
Kind Code:
A
Abstract:
Thiol derivative compounds, pharmaceutically acceptable salts, and biolabile esters thereof, useful for inhibiting metallo- beta -lactamases, bacterial enzymes which confer resistance to clinically relevant ss-lactam antibiotics, characterized by general formula (I): wherein: R<1> is selected from straight, branched, unsaturated or alicyclic alkyl, optionally substituted with from 1 to 3 Rx groups; and (CH2)nAr, where Ar is an aryl selected from the group consisting of phenyl, furanyl, thienyl, pyridyl, naphthyl, biphenyl, dibenzofuranyl, dibenzothienyl, fluorenyl and fluorenonyl, where n is 0, 1, 2 or 3, and where Ar is optionally substituted with 1 to 3 Rx groups; R<2> is selected from hydrogen; and a group of formula (II): wherein: R<3> is selected from hydrogen; straight, branched, unsaturated or alicyclic alkyl, optionally substituted with from 1 to 3 Rx groups; (CH2)nAr, where Ar is an aryl selected from phenyl, furanyl, thienyl, pyridyl, naphthyl, biphenyl dibenzofuranyl, dibenzothienyl, fluorenyl and fluorenonyl, where Ar is optionally substituted with 1 to 3 Rx groups, and where n is 0, 1, 2 or 3; and a group of formula (III): wherein: R<4> is selected from hydrogen; and straight or branched alkyl; R<5> is selected from hydrogen; straight, branched, unsaturated or alicyclic alkyl, optionally substituted with 1 to 3 Rx groups, where the alkyl group is optionally interrupted by X, where X is selected from O, S, NH and N(COCH3); allyloxy and 9-fluorenylmethyloxy; and (CH2)nAr, where Ar is selected from phenyl, furanyl, thienyl, pyridyl, naphthyl, biphenyl, dibenzofuranyl, dibenzothienyl, fluorenyl and fluorenonyl, where n is 0, 1, 2 or 3, and where Ar is optionally substituted with 1 to 3 Rx groups; and Rx is selected from OR, CN, C(O)NH2, C(O)NHR, C(O)N(R)2, OC(O)NH2, OC(O)R, CHO, SO2NH2, SOR, CF3, C(O)R, COOR, F, Cl, Br, I, OCH2Ph, NHR, N(R)2, NHCOR, NHCO2t-Bu, NHCO2allyl, NH2, and R, where R is hydrogen, C1 to C15 alkyl, or aryl. The invention is further directed to a pharmaceutical composition containing the compound, as well as a method for treating bacterial infections in animals or humans, wherein the composition can be administered in combination with a beta -lactam antibiotic.
Inventors:
Barkovec, The Ames M
Green Lee, Mark Elle
Hammond, Milton El
Heck, The Ames Buoy
Green Lee, Mark Elle
Hammond, Milton El
Heck, The Ames Buoy
Application Number:
JP2001503822A
Publication Date:
July 15, 2003
Filing Date:
June 12, 2000
Export Citation:
Assignee:
Merck End-Campany Inc.
International Classes:
C07D333/40; A61K31/198; A61K31/223; A61K31/27; A61K31/343; A61K31/381; A61K31/407; A61K31/43; A61K31/431; A61K31/4406; A61K31/445; A61K31/545; A61K45/00; A61P31/04; A61P43/00; C07C323/56; C07C327/32; C07D211/62; C07D213/56; C07D307/91; C07D333/38; (IPC1-7): C07C327/32; A61K31/198; A61K31/223; A61K31/27; A61K31/343; A61K31/381; A61K31/407; A61K31/43; A61K31/431; A61K31/4406; A61K31/445; A61K31/545; A61K45/00; A61P31/04; A61P43/00; C07D211/62; C07D213/56; C07D307/91; C07D333/40
Attorney, Agent or Firm:
Yoshio Kawaguchi (5 outside)