发明名称 Heteroaryloxyheterocyclyl compounds as PDE10 inhibitors
摘要 Heteroaryloxyheterocyclyl compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive-compulsive disorder, and the like.
申请公布号 US9376450(B2) 申请公布日期 2016.06.28
申请号 US201313892196 申请日期 2013.05.10
申请人 AMGEN INC. 发明人 Allen Jennifer R.;Horne Daniel B.;Harrington Essa Hu;Kaller Matthew R.;Monenschein Holger;Nguyen Thomas T.;Reichelt Andreas;Rzasa Robert M.
分类号 C07D491/107;C07D413/14;C07D403/04;C07D403/14;C07D487/04;C07D487/10;C07D401/04;C07D401/06;C07D405/14;C07D405/04;C07D401/14;C07D417/14;C07D471/04;C07D471/08;C07D409/14 主分类号 C07D491/107
代理机构 代理人 Lemoine Elsa D.
主权项 1. A compound of formula I:or a pharmaceutically acceptable salt thereof, wherein: X1 is CR6; X2 is N; X3 is CR3; X4 is N; X5 is CR6; the ring containing X1, X2, X3, X4, and X5 can be fused to ring A, ring B, or ring C; each having the formula:wherein each said ring A, ring B, or ring C is a fused 4- to 6-membered-saturated, -partially saturated, or -unsaturated-carbocyclic or -heterocyclic ring containing 0, 1, 2, or 3 heteroatoms; and is substituted by 0, 1, or 2 R10 groups; which are oxo, C1-6alk, C1-3haloalk, —OH, —OC1-4alk, —NH2—NHC1-4alk, —OC(═O)C1-4alk, or —N(C1-4alk)C1-4alk; W is —O—; m is 0, 1, 2, 3, or 4; each of p and q is independently 0, 1, 2, 3, 4, 5, or 6; wherein the sum of p and q is 2 to 6; the ring containing p and q contains 0 or 1 double bond; R1 is halo, C1-8alk, C1-4haloalk, —ORc, —N(Ra)C(═O)Rb, —C(═O)Ra, —C(═O)Rc, —C(═O)—O—Ra, —NRaRc, —N(Rc)C(═O)Rb, —N(Ra)C(═O)Rc, —C(═O)NRaRb, —C(═O)NRaRc, or C0-4alk-L1; wherein said C1-8alk group is substituted by 0, 1, 2 or 3 groups which are halo, C1-3 haloalk,—OH, —OC1-4alk, —NH2, —NHC1-4alk, —OC(═O)C1-4alk, or —N(C1-4alk)C1-4alk; R2 is quinolinyl, quinazolinyl, or quinoxalinyl; each of R3 and R6 is independently R1, H, halo, CN, OH, OC1-4alk, C1-4alk, or C1-4haloalk; wherein 1 or 2 of R3 and R6 must be R1; R4a is H, C1-4alk, or C1-4haloalk; each R4b is independently F, Cl, Br, CN, OH, OC1-4alk, C1-4alk, or C1-4haloalk; Ra is independently H or Rb; Rb is independently phenyl, benzyl, or C1-6alk, wherein said phenyl, benzyl, and C1-6alk are being substituted by 0, 1, 2 or 3 substituents selected from halo, C1-4alk, C1-3haloalk, —OH, —OC1-4alk, —NH2, —NHC1-4alk, —OC(═O)C1-4alk, or —N(C1-4alk)C1-4alk; Rc is C0-4alk-L4; and each of L1, L3, and L4 is independently a carbon-linked or nitrogen-linked saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic ring or a saturated, partially-saturated or unsaturated 8-, 9-, 10-, 11-, or 12-membered bicyclic ring; each said ring contains 0, 1, 2, 3, or 4 N atoms and 0, 1, or 2 atoms which are O or S; each L1, L3, and L4 is independently substituted by 0, 1, 2 or 3 R7 groups which are independently F, Cl, Br, C1-6alk, C1-4haloalk, —ORa, —OC1-4haloalk,CN, —C(═O)Rb, —C(═O)ORa, —C(═O)NRaRa, —C(═NRa)NRaRa, —OC(═O)Rb, —OC(═O)NRaRa, —OC1-6alkNRaRa, —OC1-6alkORa, —SRa, —S(═O)Rb, —S(═O)2Rb, —S(═O)2NRaRa, —NRaRa, —NRaRc, —N(Ra)C(═O)Rb, —N(Ra)C(═O)ORb, —N(Ra)C(═O)NRaRa, —N(Ra)C(═NRa)NRaRa, —N(Ra)S(═O)2Rb, —N(Ra)S(═O)2NRaRa, —NRaC2-6alkNRaRa, —NRaC1-6 alkORa, —C1-6 alkNRaRa, —C1-6 alkORa, —C1-6 alkN(Ra)C(═O)Rb, —C1-6alkOC(═O)Rb, —C1-6alkC(═O)NRaRa, —C1-6alkC(═O)ORa, or oxo.
地址 Thousand Oaks CA US
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