发明名称 Neprilysin inhibitors
摘要 In one aspect, the invention relates to compounds having the formula I:; where R1-R6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.
申请公布号 US9593110(B2) 申请公布日期 2017.03.14
申请号 US201514608686 申请日期 2015.01.29
申请人 Theravence Biopharma R&D IP, LLC 发明人 Fleury Melissa;Beausoliel Anne-Marie;Hughes Adam D.;Long Daniel D.;Wilton Donna A. A.
分类号 C07D249/04;C07D231/14;C07D263/34;C07D271/07;C07D213/81;A61K31/422;A61K31/4192;A61K31/4196;A61K31/42;A61K31/4245;C07D471/04;C07D261/18;C07D249/10;A61K31/415;A61K31/421;A61K31/44;C07D239/28;A61K31/505;C07D275/03;A61K31/425;A61K31/437;C07D403/04;A61K31/4985;C07D403/12;A61K45/06;C07D405/14;C07D309/40;C07C271/22;C07D319/06;C07D231/18;C07D231/20;C07D233/70;C07D233/90;C07D401/04;C07D235/08;C07D403/06;C07D237/14;C07D239/34;C07D405/12;C07C229/34;C07D249/12;C07D249/18;C07D261/12;C07D263/18;C07D295/10 主分类号 C07D249/04
代理机构 代理人 Hagenah Jeffrey A.;Petka Wendy
主权项 1. A compound of formula I:where: R1 is H, —C1-8alkyl, —CH(CH3)OC(O)—O-cyclohexyl, —(CH2)2-morpholinyl, or —CH2-5-methyl-[1,3]dioxol-2-one; R2 is —C0-3alkylene-NR22R23, R22 is H or —C1-6alkyl; R23 is H, —C1-6alkyl, —C1-6alkyl substituted with 1 to 6 fluoro atoms, —SO2—C1-6alkyl, —CH2OC(O)—C1-6alkyl, —C2-4alkylene-OH, —C2-4alkylene-O—CH3, or cyclopropyl optionally substituted with one or two R31 groups; or R22 and R23 are taken together to form —(CH2)2—O—(CH2)2—, a 2-oxa-6-aza-spiro[3.3]heptane ring, or an azetidine ring optionally substituted with one or two R31 groups; and each R31 is independently halo, —C1-6alkyl, —C0-2alkylene-OH, —C0-2alkylene-OC1-6alkyl, —CN, or —CONH2; R3, R4 and R5 are independently H or halo; R6 is a heterocycle selected from the group consisting of 3H-oxazol-2-one, [1,2,4]oxadiazol-5-one, [1,2,3,5]oxatriazole, dihydro-[1,2,4]triazol-3-one, [1,2,4]triazolo[1,5-α]pyridine, triazole, pyrazole, imidazole, oxazole, isoxazole, isothiazole, pyridine, oxadiazole, and pyrimidine; the heterocycle is attached at a carbon atom; and each nitrogen atom in the heterocycle is unsubstituted or substituted with an R60 group selected from the group consisting of —OH, —(CH2)2OH, —C0-2alkylene-O—C1-6alkyl, —C1-6alkyl, —CHF2, —CF3, and phenyl; and each carbon atom in the heterocycle is unsubstituted or substituted with an R61 group independently selected from the group consisting of halo, —OH, —C1-6alkyl, —C0-2alkylene-O—C1-6alkyl, —C(O)CH3, —C(O)NH(CH3), —C(O)N(CH3)2, —C3-6cycloalkyl, —CF3, —CH2SO2CH3, —NH2, —CH2NH2, —CH2N(CH3)2, pyrazine, and phenyl substituted with methyl or halo; or a pharmaceutically acceptable salt thereof.
地址 South San Francisco CA US