发明名称 Oxazine derivatives
摘要 The present invention provides, for example, a compound mentioned below as a medicament for treating or preventing the diseases induced by production, secretion or deposition of amyloid-β proteins.;A compound of the formula (I):; wherein R1, R2 a, R2 b, R3, R4 a, R4 b, ring A and the dashed lines are defined in the specification, its pharmaceutically acceptable salt or a solvate thereof.
申请公布号 US9290466(B2) 申请公布日期 2016.03.22
申请号 US201514627700 申请日期 2015.02.20
申请人 Shionogi & Co., Ltd. 发明人 Masui Moriyasu;Hori Akihiro
分类号 C07D265/08;C07D413/12;C07D498/04;A61K31/535;A61K31/5355;C07D265/06;C07D413/14 主分类号 C07D265/08
代理机构 Hamre, Schumann, Mueller & Larson, P.C. 代理人 Hamre, Schumann, Mueller & Larson, P.C.
主权项 1. A compound of formula (I): wherein ring A is a substituted benzene, R1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted acyl, cyano, carboxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, a substituted or unsubstituted carbocyclic group or a substituted or unsubstituted heterocyclic group, R2a and R2b are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkoxycarbonyl or substituted or unsubstituted carbamoyl, the above rings being optionally substituted at any available position with one or more substituents selected from the group consisting of alkyl substituted with one or more substituents selected from the substituent group α, unsubstituted alkyl and the substituent group α, R3b and R4b are each independently hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, substituted or unsubstituted acyloxy, cyano, nitro, carboxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenylsulfinyl, substituted or unsubstituted alkynylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, a substituted or unsubstituted carbocyclic group, substituted or unsubstituted carbocyclyloxy, substituted or unsubstituted carbocyclylthio, substituted or unsubstituted carbocyclylalkyl, substituted or unsubstituted carbocyclylalkoxy, substituted or unsubstituted carbocyclyloxycarbonyl, substituted or unsubstituted carbocyclylsulfinyl, substituted or unsubstituted carbocyclylsulfonyl, a substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclyloxy, substituted or unsubstituted heterocyclylthio, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heterocyclylalkoxy, substituted or unsubstituted heterocyclyloxycarbonyl, substituted or unsubstituted heterocyclylsulfinyl or substituted or unsubstituted heterocyclylsulfonyl, wherein “acyl” includes formyl, alkylcarbonyl of a carbon number of 1 to 10, alkenylcarbonyl of a carbon number of 2 to 10, alkynylcarbonyl of a carbon number of 2 to 10, carbocyclylcarbonyl and heterocyclylcarbonyl, the substituents of “substituted benzene”, “substituted or unsubstituted carbocycle”, and “substituted or unsubstituted heterocycle” in ring A, ring A′ and ring B are one or more substituents selected from (A) a group selected from the substituent group α wherein the substituent group α is a group consisting of halogen, hydroxy, alkoxy, halogenoalkoxy, hydroxyalkoxy, alkoxyalkoxy, acyl, acyloxy, carboxy, alkoxycarbonyl, amino, acylamino, alkylamino, imino, hydroxyimino, alkoxyimino, alkylthio, carbamoyl, alkylcarbamoyl, hydroxyalkylcarbamoyl, sulfamoyl, alkylsulfamoyl, alkylsulfinyl, alkylsulfonylamino, alkylsulfonylalkylamino, alkylsulfonylimino, alkylsulfinylamino, alkylsulfinylalkylamino, alkylsulfinylimino, cyano, nitro, a carbocyclic group and a heterocyclic group, each of which carbocycle and heterocycle is optionally substituted with one or more substituent selected from halogen, alkyl, hydroxy, and alkoxy; (B) alkyl substituted with one or more groups selected from the substituent group α, hydroxyimino and alkoxyimino, or unsubstituted alkyl; (C) aminoalkyl substituted with one or more groups selected from the substituent group α; alkenyl substituted with one or more substituents selected from the substituent group α, or unsubstituted alkenyl; (D) alkynyl substituted with one or more substituents selected from the substituent group α, or unsubstituted alkynyl; (E) alkoxy substituted with one or more substituents selected from the substituent group α; (F) alkoxyalkoxy substituted with one or more substituents selected from the substituent group α; (G) alkenyloxy substituted with one or more substituents selected from the substituent group α, or unsubstituted alkenyloxy; (H) alkoxyalkenyloxy substituted with one or more substituents selected from the substituent group α; (I) alkynyloxy substituted with one or more substituents selected from the substituent group α, unsubstituted alkynyloxy; (J) alkoxyalkynyloxy substituted with one or more groups selected from the substituent group α; (K) alkylthio substituted with one or more substituents selected from the substituent group α, or unsubstituted alkylthio; (L) alkenylthio substituted with one or more substituents selected from the substituent group α, or unsubstituted alkenylthio; (M) alkynylthio substituted with one or more substituents selected from the substituent group α, or unsubstituted alkynylthio; (N) alkylamino substituted with one or more substituents selected from the substituent group α; (O) alkenylamino substituted with one or more substituents selected from the substituent group α; (P) alkynylamino substituted with one or more substituents selected from the substituent group α; (Q) aminooxy substituted with one or more substituents selected from the substituent group α and alkylidene, or unsubstituted aminooxy; (R) acyl substituted with one or more substituents selected from the substituent group α; (S) alkylsulfonyl substituted with one or more substituents selected from the substituent group α, or unsubstituted alkylsulfonyl; (T) alkylsulfinyl substituted with one or more substituents selected from the substituent group α, or unsubstituted alkylsulfinyl; (U) alkylsulfamoyl substituted with one or more substituents selected from the substituent group α; (V) a carbocyclic group substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl; (W) a heterocyclic group substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl; (X) carbocyclylalkyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylalkyl; (Y) heterocyclylalkyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylalkyl; (Z) carbocyclyloxy substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclyloxy; (AA) heterocyclyloxy substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclyloxy; (AB) carbocyclylalkoxy substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylalkoxy; (AC) heterocyclylalkoxy substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylalkoxy; (AD) carbocyclylalkoxycarbonyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylalkoxycarbonyl; (AE) heterocyclylalkoxycarbonyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylalkoxycarbonyl; (AF) carbocyclylthio such substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylthio; (AG) heterocyclylthio substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylthio; (AH) carbocyclylamino substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylamino; (AI) heterocyclylamino substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylamino; (AJ) carbocyclylalkylamino substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl or unsubstituted carbocyclylalkylamino; (AK) heterocyclylalkylamino substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylalkylamino; (AL) carbocyclylsulfamoyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylsulfamoyl; (AM) heterocyclylsulfamoyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylsulfamoyl; (AN) carbocyclylsulfonyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylsulfonyl; (AO) heterocyclylsulfonyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylsulfonyl; (AP) carbocyclylcarbamoyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylcarbamoyl; (AQ) heterocyclylcarbamoyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylcarbamoyl; (AR) carbocyclylalkylcarbamoyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclylalkylcarbamoyl; (AS) heterocyclylalkylcarbamoyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclylalkylcarbamoyl; (AT) carbocyclyloxycarbonyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted carbocyclyloxycarbonyl; (AU) heterocyclyloxycarbonyl substituted with one or more substituents selected from the substituent group α, azide, alkyl and halogenoalkyl, or unsubstituted heterocyclyloxycarbonyl; (AV) alkylenedioxy substituted with halogen, or unsubstituted alkylenedioxy; (AW) oxo; and (AX) azide; and ring A may be selected from the followings: wherein ring A′ is substituted or unsubstituted benzene, ring B is substituted or unsubstituted carbocycle or substituted or unsubstituted heterocycle wherein the substituents are defined above, L1, L2, and L3 are each independently a bond, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene or substituted or unsubstituted alkynylene, ═W1 is ═O, ═S, or ═NR9, W2 is O, S, or N(R8), R8 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or substituted or unsubstituted acyl, R9 is hydrogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or substituted or unsubstituted acyl, when ring A is (i), then the constituent carbon atom of L1 and the constituent carbon atom of L2, or the constituent carbon atom of L1 and the nitrogen atom of W2 may be connected with substituted or unsubstituted alkylene to form a ring, when ring A is (ii), then the constituent carbon atom of L1 and the constituent carbon atom of L2, or the nitrogen atom of W2 and the constituent carbon atom of L2 may be connected with substituted or unsubstituted alkylene to form a ring, when ring A is (iii), then two nitrogen atoms of W2 may be connected with substituted or unsubstituted alkylene to form a ring, when ring A is (vi), then the constituent carbon atom of L′ and the constituent carbon atom of L2 may be connected by substituted or unsubstituted alkylene to form a ring, p is 1 or 2, and when multiple L3, multiple W2, or multiple R9 are present, each of them may be independently different; the substituents of “substituted or unsubstituted alkyl”, “substituted or unsubstituted alkoxy”, “substituted or unsubstituted alkoxycarbonyl”, “substituted or unsubstituted alkylthio”, “substituted or unsubstituted alkylsulfonyl”, “substituted or unsubstituted alkylsulfinyl”, “substituted or unsubstituted alkenyl”, “substituted or unsubstituted alkenyloxy”, “substituted or unsubstituted alkenyloxycarbonyl”, “substituted or unsubstituted alkenylthio”, “substituted or unsubstituted alkenylsulfinyl”, “substituted or unsubstituted alkenylsulfonyl”, “substituted or unsubstituted alkynyl”, “substituted or unsubstituted alkynyloxy”, “substituted or unsubstituted alkynylthio”, “substituted or unsubstituted alkynyloxycarbonyl”, “substituted or unsubstituted alkynylsulfinyl”, “substituted or unsubstituted alkynylsulfonyl”, “substituted or unsubstituted alkylene”, “substituted or unsubstituted alkenylene”, and “substituted or unsubstituted alkynylene” are one or more substituents selected from a substituent group α: the substituents of “substituted or unsubstituted acyl” and “substituted or unsubstituted acyloxy” are one or more substituents selected from the substituent group α, and the ring portions of carbocyclylcarbonyl and heterocyclylcarbonyl may be substituted with one or more substituents selected from alkyl, substituent group α, and alkyl substituted with one or more substituents selected from substituent group α; the substituent in “substituted or unsubstituted amino”, “substituted or unsubstituted carbamoyl”, “substituted or unsubstituted thiocarbamoyl” and “substituted or unsubstituted sulfamoyl” are one or two substituents selected from alkyl, acyl, hydroxy, alkoxy, alkoxycarbonyl, carbocyclic group and heterocyclic group; the substituents of “substituted or unsubstituted carbocyclic group”, “substituted or unsubstituted carbocyclylthio”, “substituted or unsubstituted carbocyclyloxycarbonyl”, “substituted or unsubstituted carbocyclyloxy”, “substituted or unsubstituted carbocyclylsulfinyl”, “substituted or unsubstituted carbocyclylsulfonyl”, “substituted or unsubstituted carbocycle”, “substituted or unsubstituted heterocyclic group”, “substituted or unsubstituted heterocyclyloxy”, “substituted or unsubstituted heterocyclylthio”, “substituted or unsubstituted heterocyclyloxycarbonyl”, “substituted or unsubstituted heterocycylsulfinyl”, “substituted or unsubstituted heterocyclylsulfonyl”, and “substituted or unsubstituted heterocycle” in other than the ring A and ring B are one or more substituents selected from the substituent group α, unsubstituted alkyl, and alkyl substituted with one or more substituents selected from the substituent group α; its pharmaceutically acceptable salt or a solvate thereof.
地址 Osaka JP