发明名称 Chromenone analogs as sirtuin modulators
摘要 The present invention relates to novel chromenone analog sirtuin modulator compounds of Formula (I):; or pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions and treatment methods and combination therapies thereof for use in increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity.
申请公布号 US8987258(B2) 申请公布日期 2015.03.24
申请号 US200913121410 申请日期 2009.09.29
申请人 发明人 Oalmann Christopher;Perni Robert B.;Vu Chi B.
分类号 C07D417/12;C07D417/14;C07D405/12;C07D405/14;A61K31/5377;A61K31/427;A61K31/4439;A61K31/4025;A61K31/497;A61K31/353;A61K45/06;C07D311/30;A61P3/00;A61P3/10 主分类号 C07D417/12
代理机构 代理人 Hsu Grace C.;Lemanowicz John
主权项 1. A compound of the formula (II):or a salt thereof:wherein: each R20 is independently selected from hydrogen, halo, —C≡N, fluoro-substituted C1-C2 alkyl, —O—(C1-C2) fluoro-substituted alkyl, —S—(C1-C2) fluoro-substituted alkyl, C1-C4 alkyl, —S—(C1-C4) alkyl, C3-C7 cycloalkyl, —(C1-C2) alkyl-N(R13)(R13), —O—CH2CH(OH)CH2OH, —O—(C1-C3)alkyl-N(R13)(R13), and —N(R13)(R13); R11 is selected from:  or R11 is selected from:  or R11 is selected from wherein: R11 is optionally substituted with one to two substitutents independently selected from halo, —C≡N, C1-C4 alkyl, ═O, C3-C7 cycloalkyl, fluoro-substituted C1-C4 alkyl, —O—R13, —S—R13, —(C1-C4 alkyl)-N(R13)(R13), —N(R13)(R13), —O—(C1-C4 alkyl)-N(R13)(R13), —(C1-C4 alkyl)-O—(C1-C4 alkyl)-N(R13)(R13), —C(O)—N(R13)(R13), and —(C1-C4 alkyl)-C(O)—N(R13)(R13), and when R11 is phenyl, R11 is also optionally substituted with 3,4-methylenedioxy, fluoro-substituted 3,4-methylenedioxy, 3,4-ethylenedioxy, fluoro-substituted 3,4-ethylenedioxy, O-(saturated heterocycle), fluoro-substituted-O-(saturated heterocycle), or C1-C4 alkyl-substituted 0-(saturated heterocycle); wherein:each R13 is independently selected from hydrogen and —C1-C4 alkyl; ortwo R13 are taken together with the nitrogen atom to which they are bound to form a 4- to 8-membered saturated heterocycle optionally comprising one additional heteroatomic unit selected from NH, S, S(═O), S(═O)2, and O;wherein:when R13 is alkyl, the alkyl is optionally substituted with one or more substituents selected from —OH, fluoro, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —NH(CH2CH2OCH3), and —N(CH2CH2OCH3)2 andwhen two R13 are taken together with the nitrogen atom to which they are bound to form a 4- to 8-membered saturated heterocycle, the saturated heterocycle is optionally substituted at any carbon atom with —OH, —C1-C4 alkyl, fluoro, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —NH(CH2CH2OCH3), or —N(CH2CH2OCH3)2, and optionally substituted at any substitutable nitrogen atom with —C1-C4 alkyl, fluoro-substituted C1-C4 alkyl, or —(CH2)2—O—CH3; R12 is selected from a 5-7 membered aryl or heteroaryl other than optionally substituted tetrazolyl; wherein:R12 is optionally substituted with one or more substitutents independently selected from halo, —C≡N, C1-C4 alkyl, C3-C7 cycloalkyl, C1-C2 fluoro-substituted alkyl, —O—R13, —S—R13, —S(O)—R13, —S(O)2—R13, —(C1-C4 alkyl)-N(R13)(R13), —N(R13)(R13), —O—(C1-C4 alkyl)-N(R13)(R13), —(C1-C4 alkyl)-O—(C1-C4 alkyl)-N(R13)(R13), —C(O)—N(R13)(R13), —(C1-C4 alkyl)-C(O)—N(R13)(R13), —O-phenyl, phenyl, and a second heterocycle, and when R12 is phenyl, R12 may also be optionally substituted with 3,4-methylenedioxy, fluoro-substituted 3,4-methylenedioxy, 3,4-ethylenedioxy, or fluoro-substituted 3,4-ethylenedioxy, or —O-(saturated heterocycle), wherein any phenyl, second heterocycle or saturated heterocycle portion of a substituent of R12 is optionally substituted with halo, —C≡N, C1-C4 alkyl, fluoro-substituted C1-C2 alkyl, —O—(C1-C2) fluoro-substituted alkyl, —O—(C1-C4) alkyl, —S—(C1-C4) alkyl, —S—(C1-C2) fluoro-substituted alkyl, —NH—(C1-C4) alkyl and —N—(C1-C4)2 alkyl; R14 is selected from hydrogen, C1-C4 alkyl, C1-C4 fluoro-substituted alkyl, C1-C4 alkyl-N(R13)(R13), C1-C4 alkyl-C(O)—N(R13)(R13), C1-C4 alkyl-O—R13, and C1-C4 alkyl-NR13—C(O)R13; X1 is —NH—C(═O)-†; wherein: † represents where X1 is bound to R11; andeach of R15 and R16 is independently selected from hydrogen, C1-C4 alkyl, —CF3 and (C1-C3 alkyl)-CF3wherein: when R14 is C1-C4 alkyl, R12 is other than optionally substituted phenyl.
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