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1. 发明申请

WO2010092342A1 ORGANOSILICON COMPOUNDS AND THEIR USE AS THE MODULATORS OF THE TRPV1 RECEPTOR 审中-公开
标题翻译：有机硅化合物及其作为TRPV1受体调节剂的用途
公开(公告)号：WO2010092342A1
公开(公告)日：2010-08-19
申请号：PCT/GB2010/000246
申请日：2010-02-10
申请人： TAKEDA PHARMACEUTICAL COMPANY LIMITED , AYSCOUGH, Andrew Paul , SHOWELL, Graham Andrew , TEALL, Martin Richard , TEMPLE, Hannah Elizabeth , AHMED, Saleh
发明人： AYSCOUGH, Andrew Paul , SHOWELL, Graham Andrew , TEALL, Martin Richard , TEMPLE, Hannah Elizabeth , AHMED, Saleh
IPC分类号： C07F7/08 , A61K31/695
CPC分类号： C07F7/0814
摘要： A compound having the Formula (1): wherein: X 1 , X 2 , X 3 and X 4 independently represent CH or N; R 1 , R 2 and R 3 independently represent C 1-6 alkyl, C 3-8 cycloalkyl or C 3-8 cycloalky IC 1-6 alkyl, each of which groups may be optionally substituted with one or more substituents independently selected from halogen and haloC 1-6 alkyl; R 4 , R 5 , R 6 , R 7 , R 8 and R 9 independently represent H, C 1-6 alkyl, C 3-8 cycloalkyl or -Q I -OR 14 , or R 4 and R 9 may join to form a bridging C 1-6 alkylene chain; R 10 represents aryl or heteroaryl, each of which may be optionally substituted by one or more substituents, independently selected from halogen, C 1-6 alkyl, haloC 1-6 alkyl, hydroxyC 1-6 alkyl, haloC 1-6 alkoxy, cyano, -Q 2 -CO 2 R 12 , -Q 2 -COR 12 , -Q 2 -CONR 12 R 13 , -Q 2 -OR 12 , -Q 2 -NR 12 Rn, -Q 2 -NR 12 SO 2 R 13 , -Q 2 - NR 12 COR 13 , -Q 2 -SO 2 NR 12 R 13 , -Q 2 -S(O) m R 12 , -Y-aryl, -Y-heteroaryl, -Y-C 3-8 cycloalkyl and -Y-heterocyclyl; Q 1 and Q 2 independently represent a covalent bond, C 1-6 alkylene, or 1-6 alkylene substituted with hydroxy; R 12 and R 13 independently represent a H atom, or a C 1-6 alkyl or C 3-8 cycloalkyl group, in which each group may be optionally substituted with one or more C 1-6 alkoxy; or when R 12 and R 13 are attached to the same nitrogen atom they may join to form a nitrogen containing heterocyclyl ring, which may be optionally substituted with one or more substituents independently selected from C 1-6 alkyl and C 1-6 alkoxy; R 14 represents a H atom, or a C 1-6 alkyl or C 3-8 cycloalkyl group, in which each group may be optionally substituted with one or more C 1-6 alkoxy; Y represents a covalent bond, C 1-6 alkylene, or -O-. m represents 0, 1 or 2; R 11 , which is optionally present and may be attached to any available carbon atom X 1 to X 4 instead of H, represents halogen, haloC 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, cyano or C 1-6 alkyl which may be optionally substituted with one or more substituents independently selected from halogen, haloC1-6 alkyl and OR 16 ; q represents 0, 1 or 2; W represents -(CH 2 ) n -, which may be optionally substituted with one or more substituents independently selected from C 1-6 alkyl, C 3-8 cycloalkyl and -Q 3 -OR 15 ; n represents 1 or 2; Q 3 represents a covalent bond or C1-6 alkylene; R 15 represents H, C 1-6 alkyl, or C 3-8 cycloalkyl; R 16 is as defined for R 14 ; or a pharmaceutically acceptable salt or ester thereof. Uses of the compounds as modulators of the TrpVl receptor are also disclosed.
摘要翻译：具有式（1）的化合物：其中：X 1，X 2，X 3和X 4独立地表示CH或N; R 1，R 2和R 3独立地表示C 1-6烷基，C 3-8环烷基或C 3-8环烷基IC 1-6烷基，其各自可以任选地被一个或多个独立地选自卤素和卤代C 1-6烷基的取代基取代; R 4，R 5，R 6，R 7，R 8和R 9独立地表示H，C 1-6烷基，C 3-8环烷基或-QI-OR 14，或者R 4和R 9可以连接形成桥连C 1-6亚烷基链; R 10表示芳基或杂芳基，其各自可以任选被一个或多个独立地选自卤素，C 1-6烷基，卤代C 1-6烷基，羟基C 1-6烷基，卤代C 1-6烷氧基，氰基，-Q 2 -CO 2 R 12， -Q2-COR12，-Q2-CONR12R13，-Q2-OR12，-Q2-NR12Rn，-Q2-NR12SO2R13，-Q2- NR12COR13，-Q2-SO2NR12R13，-Q2-S（O）mR12，-Y-芳基， Y-杂芳基，-Y-C 3-8环烷基和-Y-杂环基; Q1和Q2独立地表示共价键，C1-6亚烷基或被羟基取代的1-6个亚烷基; R 12和R 13独立地表示H原子或C 1-6烷基或C 3-8环烷基，其中每个基团可以任选被一个或多个C 1-6烷氧基取代; 或当R 12和R 13连接到相同的氮原子上时，它们可以连接形成含氮杂环基环，其可任选地被一个或多个独立地选自C 1-6烷基和C 1-6烷氧基的取代基取代; R 14表示H原子或C 1-6烷基或C 3-8环烷基，其中各基团可任选被一个或多个C 1-6烷氧基取代; Y表示共价键，C 1-6亚烷基或-O-。 m表示0,1或2; 任选存在并且可以连接到任何可用的碳原子X 1至X 4而不是H的R 11表示卤素，卤代C 1-6烷基，C 1-6烷氧基，卤代C 1-6烷氧基，氰基或C 1-6烷基，其可任选被一个或更多取代基，其独立地选自卤素，卤代C 1-6烷基和OR 16; q表示0,1或2; W表示 - （CH 2）n - ，其可任选被一个或多个独立地选自C 1-6烷基，C 3-8环烷基和-Q 3 -OR 15的取代基取代; n表示1或2; Q3表示共价键或C 1-6亚烷基; R 15表示H，C 1-6烷基或C 3-8环烷基; R16如R14所定义; 或其药学上可接受的盐或酯。还公开了化合物作为TrpV1受体的调节剂的用途。

2. 发明申请

WO1995011880A1 SUBSTITUTED AMIDES AS TACHYKININ ANTAGONISTS 审中-公开
标题翻译：作为TACHYKININ ANTAGONISTS的替代药物
公开(公告)号：WO1995011880A1
公开(公告)日：1995-05-04
申请号：PCT/GB1994002342
申请日：1994-10-24
申请人： MERCK SHARP & DOHME LIMITED , CHAMBERS, Mark, Stuart , HARRISON, Timothy , OWENS, Andrew, Pate , TEALL, Martin, Richard , WILLIAMS, Brian, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07C233/29
CPC分类号： C07D233/64 , C07C233/11 , C07C233/13 , C07C233/22 , C07C235/34 , C07C235/46
摘要： A class of substituted amide compounds of formula (I), are antagonists of tachykinins, especially substance P, and are therefore of use in the treatment or prevention of physiological disorders associated with an excess of tachykinins, such as inflammation, pain, migraine and emesis. In formula (I) Ar and Ar each independently represents a phenyl group optionally substituted by one, two or three groups selected from halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkylC1-4alkyl, trifluoromethyl, cyano, nitro, SR , SOR , SO2R , OR , NR R , NR COR , NR CO2R , CO2R or CONR R , wherein R and R are each independently H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkylC1-4alkyl, phenyl or trifluoromethyl; Q represents Ar or a group of formula Het-(CH2)n-, where n is 1 or 2 and Het is a five or six membered nitrogen containing heterocyclic group with 1, 2 or 3 heteroatoms selected from nitrogen, oxygen or sulphur with at most one oxygen or sulphur atom, which group may have the residue of a further 5 or 6 membered aromatic ring fused thereto, and which group may be optionally substituted by a group selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, oxo, thioxo, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, OR , SR , SOR , SO2R , NR R , NR COR , NR CO2R , CO2R , CONR R or phenyl optionally substituted by 1, 2 or 3 groups selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, OR , SR , SOR , SO2R , NR R , NR COR , CO2R , or CONR R , where R and R are each independently H, C1-6alkyl, trifluoromethyl or phenyl; X represents a -CO-NR- or -NR-CO- group, where R is hydrogen, C1-6alkyl, or methyl substituted by a C2-6alkenyl or C2-6alkynyl group; one of Y and Y is a bond or C1-4alkylene group and the other is a C1-4alkylene group; with the proviso that when Ar and Q are dimethoxyphenyl, -Y -X-Y -Ar is not -CH2CON(CH3)CH2C6H5.
摘要翻译：一类取代的式（I）酰胺化合物是速激肽，特别是物质P的拮抗剂，因此可用于治疗或预防与超速激肽相关的生理紊乱症，例如炎症，疼痛，偏头痛和呕吐。在式（I）中，Ar 1和Ar 2各自独立地表示任选被一个，两个或三个选自卤素，C 1-6烷基，C 2-6烯基，C 2-6炔基，C 3-6环烷基，C 3 -6环烷基C 1-4烷基，三氟甲基，氰基，硝基，SR a，SOR a，SO 2 R a，OR a，NR a R b，NR a COR b，NR 其中R a和R b各自独立地为H，C 1-6烷基，C 2-6烯基，C 2-6炔基，C 3 -C 10环烷基 C 3-6环烷基C 1-4烷基，苯基或三氟甲基; Q表示Ar 1或式Het-（CH 2）n - 的基团，其中n为1或2，Het为含有1,2或3个选自氮，氧或氧的杂原子的5或6元含氮杂环基具有至多一个氧或硫原子的硫，该基团可以具有与其稠合的另外5或6元芳环的残基，该基团可以任选地被选自C 1-6烷基，C 2-6烯基， 6-炔基，C3-7环烷基，C3-7环烷基C 1-4烷基，氧代，硫代，卤素，氰基，硝基，三氟甲基，三甲基甲硅烷基，OR c，SR c，SOR c，SO 2 R c，NR c， R d，NR c，C d，NR c CO 2 R d，CO 2 R c，CONR c R d或任选被1,2或3个选自C 1的基团取代的苯基 C 1-6烷基，C 2-6烯基，C 2-6炔基，C 3-7环烷基，C 3-7环烷基C 1-4烷基，卤素，氰基，硝基，三氟甲基，三甲基甲硅烷基，OR c， NR c，R c，R c，R d，CO 2 R c或CONR c R d，其中R c和R d各自独立地为H，Cl -6-烷基，三氟甲基或苯基; X表示-CO-NR-或-NR-CO-基，其中R是氢，C 1-6烷基或被C 2-6烯基或C 2-6炔基取代的甲基; Y 1和Y 2之一是键或C 1-4亚烷基，另一个是C 1-4亚烷基; 条件是当Ar 1和Q是二甲氧基苯基时，-Y 1 -X-Y 2 -Ar 2不是-CH 2 CON（CH 3）CH 2 C 6 H 5。

3. 发明申请

WO1994003429A1 SUBSTITUTED AMINES AS TACHYKININ RECEPTOR ANTAGONISTS 审中-公开
标题翻译：作为TACHYKININ受体拮抗剂的替代性氨基酸
公开(公告)号：WO1994003429A1
公开(公告)日：1994-02-17
申请号：PCT/GB1993001601
申请日：1993-07-28
申请人： MERCK SHARP & DOHME LIMITED , TEALL, Martin, Richard
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D213/40
CPC分类号： C07D213/40 , C07D307/52
摘要： Compounds of formula (I), and salts and prodrugs thereof, wherein Q is optionally substituted phenyl or benzhydryl; X and Y are each H or together form a group =O; Z is O, S or NR9, where R9 is H or C1-6alkyl; R1 represents H or C1-6alkyl; R2 represents C1-6alkyl substituted by CONR7(CH2)pR8 (where R7 is H or C1-6alkyl, R8 is optionally substituted heteroaryl and p is 0, 1, 2, 3, 4, 5 or 6); R3 represents H, C1-6alkyl or C2-6alkynyl; R4 represents H, C1-6alkyl or optionally substituted phenyl; R5 represents optionally substituted phenyl; R6 is H or C1-6alkyl; and q is 0, 1, 2 or 3; are tachykinin antagonists useful in therapy.
摘要翻译：式（I）化合物及其盐和前药，其中Q为任选取代的苯基或二苯甲基; X和Y各自为H或一起形成基团= O; Z是O，S或NR 9，其中R 9是H或C 1-6烷基; R1表示H或C1-6烷基; R 2表示被CONR 7（CH 2）p R 8取代的C 1-6烷基（其中R 7为H或C 1-6烷基，R 8为任选取代的杂芳基且p为0,1,2,3,4,5或6）。 R3表示H，C1-6烷基或C2-6炔基; R 4表示H，C 1-6烷基或任选取代的苯基; R5代表任选取代的苯基; R6是H或C1-6烷基; q为0,1,2或3; 是用于治疗的速激肽拮抗剂。

4. 发明申请

WO2010007382A8 BENZAZEPINE DERIVATIVES AND THEIR USE AS HSTAMINE H3 ANTAGONISTS 审中-公开
标题翻译：苯并噻吩衍生物及其作为HSTAMINE H3拮抗剂的用途
公开(公告)号：WO2010007382A8
公开(公告)日：2010-03-18
申请号：PCT/GB2009001774
申请日：2009-07-17
申请人： TAKEDA PHARMACEUTICAL , POONI PARMINDER KAUR , MERCHANT KEVIN JOHN , KERR CATRINA , CROSBY STUART RICHARD , OKAWA TOMOHIRO , SASAKI MITSURU , GOTOU MIKA , SHOWELL GRAHAM ANDREW , TEALL MARTIN RICHARD
发明人： POONI PARMINDER KAUR , MERCHANT KEVIN JOHN , KERR CATRINA , CROSBY STUART RICHARD , OKAWA TOMOHIRO , SASAKI MITSURU , GOTOU MIKA , SHOWELL GRAHAM ANDREW , TEALL MARTIN RICHARD
IPC分类号： C07D223/16 , A61K31/55 , A61P25/18 , C07D401/06 , C07D401/12 , C07D401/14 , C07D403/12 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , C07D413/12 , C07D417/12
CPC分类号： C07D403/12 , C07D223/16 , C07D401/06 , C07D401/12 , C07D401/14 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , C07D413/12 , C07D417/12
摘要： A compound having the formula (1) wherein: R1 is a group selected from C3-8 cycloalkyl, C1-6 alkyl, C1-6 alkylene-C3-8 cycloalkyl, each of which groups may optionally be substituted with C1-6 alkyl, halogen, haloC1-6 alkyl or OR15, or R1 is heterocyclyl, optionally substituted with C1-6 alkyl, haloC1-6 alkyl or OR15; n is 0, 1, 2, 3 or 4, the alkylene group -(CH2)n- formed thereby being optionally substituted with a group selected from C1-4 alkyl, C3-8 cycloalkyl and arylsulfonyl; A is a group selected from -N(R2)CO-, -CON(R2)-, -OC(O)-, -C(O)O-, -CO-, -C(R2)(OR3)-, -C(=N-O-R3)-, - C(=CR2R3)-, -C3-8 cycloalkylene-, -C(R2)(haloC1-6 alkyl)-, C1-4 alkylene and -C(OR3)(haloC1-6 alkyl)-; R2 and R3 are each independently selected from H, C1-6 alkyl, and C3-8 cycloalkyl, or, when A is -N(R2)CO- and X is absent, R2 may form, together with the adjacent nitrogen atom and Z, an N-containing heterocyclyl group, which may optionally be substituted; X is absent or is C1-4 alkylene or C2-4 alkenylene, each of which may optionally be substituted with one or more C1-4 alkyl groups, OR16, halogen or haloC1-6 alkyl; Z is selected from aryl, heteroaryl, C3-8 cycloalkyl, and heterocyclyl, each of which may optionally be substituted by a group selected from -Y-aryl, -Y-heteroaryl, -Y-C3-8 cycloalkyl and -Y-heterocyclyl, or, when X is present, Z may be H, or, when X is absent and A is -C(R2)(OR3)- or -N(R2)CO-, Z may be H, or, when A is -N(R2)CO- and X is absent, Z may form, together with the adjacent nitrogen atom and R2, an N-containing heterocyclyl group which may optionally be substituted, wherein, when A is -CO-, Z is linked to X or A via a carbon atom and wherein, when A is -N(R2)CO- and Z is H, R1 is C3-8 cycloalkyl; and Y represents a bond, C1-6 alkylene, CO, NR14, COC2-6 alkenylene, O, SO2 or NHCOC1-6 alkylene; wherein said cycloalkyl, aryl, heteroaryl and heterocyclyl groups Z may be optionally substituted by one or more substituents which may be the same or different, and which are selected from halogen, haloC1-6 alkyl, hydroxy, cyano, nitro, =O, -R4, -CO2R4, -COR4, -NR5R6, -C1-6 alkyl-NR5R6, -C3-8 cycloalkyl-NR5R6, - CONR12R13, -NR12COR13, -NR5SO2R6, -OCONR5R6, -NR5CO2R6, -NR4CONR5R6 or -SO2NR5R6- SHR8, -alkyl-OR8, -SOR8, -OR9, -SO2R9, -OSO2R9, -alkyl-SO2R9, -alkyl-CONHR9, -alkyl-SONHR9, -alkyl-COR10, -CO-alkyl-R10, -O-alkyl-R11 (wherein R4, R5 and R6 independently represent hydrogen, C1-6 alkyl, -C3-8 cycloalkyl, -C1-6 alkylene-C3-8 cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R8 represents C1-6 alkyl, wherein R9 represents C1-6 alkyl or aryl, wherein R10 represents aryl, wherein R11 represents C3-8 cycloalkyl or aryl, R12, R13, R14, R15 and R16 each independently represent H or C1-6 alkyl, and wherein -NR5R6 and -NR12R13 may represent a nitrogen containing heterocyclyl group); wherein said R4, R5, R6 R8, R9, R11 and R11 groups may be optionally substituted by one or more substituents which may be the same or different, and which are selected from the group consisting of halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, cyano, amino, =O or trifluoromethyl; and wherein substituents of Z selected from -Y-aryl, -Y-heteroaryl, -Y-C3-8cycloalkyl and -Y-heterocyclyl may be optionally substituted by one or more substituents selected from =O, hydroxy, cyano, nitro, halogen, haloC1-6 alkyl and C1-6alkyl; and wherein, when A is C1-4 alkylene, said cycloalkyl, aryl, heteroaryl or heterocyclyl group Z (such as a heterocyclyl group Z) is substituted at least with hydroxy, CF3, or =0; and wherein, when A is CON(R2) n is 1; or a pharmaceutically acceptable salt or ester thereof, provided that: when A is -CO-, R1 is CH3, C3-8 cycloalkyl-substituted C1-6 alkylene or n-butyl, n is 0 and X is -CH2CH2-, Z is not N-benzyl substituted 4-piperidinyl, N-(3-fluorobenzyl)-substituted 4-piperidinyl or N-acetyl substituted 4-piperidinyl; when A is -OC(O)-, R1 is cyclobutyl, n is 0 and X is -CH2CH2-, Z is not H; when A is -OC(O)-, R1 is n-propyl, n is 0 and X is -CH2-, Z is not H; and when A is -CO-, R1 is CH3, n is 0 and X is CH2, Z is not H.
摘要翻译：具有式（1）的化合物，其中：R 1是选自C 3-8环烷基，C 1-6烷基，C 1-6亚烷基-C 3-8环烷基，其各自可以任选被C 1-6烷基取代，卤素，卤代C 1-6烷基或OR 15，或R 1是任选被C 1-6烷基，卤代C 1-6烷基或OR 15取代的杂环基; n为0,1,2,3或4，由此形成的亚烷基 - （CH 2）n任选被选自C 1-4烷基，C 3-8环烷基和芳基磺酰基的基团取代; A是选自-N（R2）CO-，-CON（R2） - ，-OC（O） - ， - （O）O-，-CO-，-C（R2）（OR3） -C（= NO-R 3） - ， - C（= CR 2 R 3） - ， - C 3-8亚环烷基 - ， - C（R 2）（卤代C 1-6烷基） - ，C 1-4亚烷基和-C（OR 3） -6烷基） - ; R2和R3各自独立地选自H，C1-6烷基和C3-8环烷基，或当A是-N（R2）CO-且X不存在时，R2可以与相邻的氮原子和Z ，可以任选被取代的含N的杂环基; X不存在或是C 1-4亚烷基或C 2-4亚烯基，其各自可以任选被一个或多个C 1-4烷基，OR 16，卤素或卤代C 1-6烷基取代; Z选自芳基，杂芳基，C 3-8环烷基和杂环基，其各自可任选被选自-Y-芳基，-Y-杂芳基，-Y-C 3-8环烷基和-Y-杂环基或当X存在时，Z可以是H，或者当X不存在且A是-C（R 2）（OR 3） - 或-N（R 2）CO-时，Z可以是H，或者当A是 -N（R2）CO-和X不存在，Z可以与相邻的氮原子一起形成，R 2可以任选被取代的含N的杂环基，其中当A是-CO-时，Z连接到 X或A通过碳原子，并且其中当A是-N（R 2）CO-且Z是H时，R 1是C 3-8环烷基; Y表示键，C 1-6亚烷基，CO，NR 14，COC 2-6亚烯基，O，SO 2或NHCOC 1-6亚烷基; 其中所述环烷基，芳基，杂芳基和杂环基基团Z可以任选地被一个或多个可以相同或不同的取代基取代，并且选自卤素，卤代C 1-6烷基，羟基，氰基，硝基，= O - R4，-CO 2 R 4，-COR 4，-NR 5 R 6，-C 1-6烷基-NR 5 R 6，-C 3-8环烷基-NR 5 R 6，-CONR 12 R 13，-NR 12 COR 13，-NR 5 SO 2 R 6，-OCONR 5 R 6，-NR 5 CO 2 R 6，-NR 4 CONR 5 R 6或-SO 2 NR 5 R 6 -SHR 8， - 烷基-OR 8，-SOR 8，-OR 9，-SO 2 R 9，-OSO 2 R 9， - 烷基-SO 2 R 9 - - 烷基-CONHR 9 - - 烷基-SHHR 9， - 烷基-CON10，-CO-烷基-R10，-O-烷基-R11 （其中R 4，R 5和R 6独立地表示氢，C 1-6烷基，-C 3-8环烷基，-C 1-6亚烷基-C 3-8环烷基，芳基，杂环基或杂芳基，其中R 8表示C 1-6烷基， C 1-6烷基或芳基，其中R 10表示芳基，其中R 11表示C 3-8环烷基或芳基，R 12，R 13，R 14，R 15和R 16各自独立地表示H或C 1-6烷基，并且其中-NR 5 R 6和-NR 12 R 13可以表示含氮杂环基）; 其中所述R 4，R 5，R 6，R 8，R 9，R 11和R 11基团可以任选地被一个或多个可以相同或不同的取代基取代，并且选自卤素，羟基，C 1-6烷基， C 1-6烷氧基，氰基，氨基，= O或三氟甲基; 并且其中选自-Y-芳基，-Y-杂芳基，-Y-C3-8环烷基和-Y-杂环基的Z的取代基可以任选地被一个或多个选自以下的取代基取代：选自= O，羟基，氰基，硝基，卤素，卤代C 1-6烷基和C 1-6烷基; 并且其中当A为C 1-4亚烷基时，所述环烷基，芳基，杂芳基或杂环基Z（例如杂环基Z）至少被羟基，CF 3或= 0取代; 并且其中当A是CON（R2）时，n是1; 或其药学上可接受的盐或酯，条件是：当A为-CO-时，R 1为CH 3，C 3-8环烷基取代的C 1-6亚烷基或正丁基，n为0且X为-CH 2 CH 2 - ，Z为不是N-苄基取代的4-哌啶基，N-（3-氟苄基）取代的4-哌啶基或N-乙酰基取代的4-哌啶基; 当A为-OC（O） - 时，R1为环丁基，n为0，X为-CH2CH2-，Z为H; 当A为-OC（O） - 时，R 1为正丙基，n为0且X为-CH 2 - ，Z不为H; 当A为-CO-时，R 1为CH 3，n为0，X为CH 2，Z为H。

5. 发明申请

WO2005013985A1 TREATMENT FOR ALZHEIMER'S DISEASE AND RELATED CONDITIONS 审中-公开
标题翻译：治疗阿尔茨海默病和相关情况
公开(公告)号：WO2005013985A1
公开(公告)日：2005-02-17
申请号：PCT/GB2004/003286
申请日：2004-07-29
申请人： MERCK SHARP & DOHME LIMITED , BEHER, Dirk , BETTATI, Michela , CHECKSFIELD, Graham, David , CHURCHER, Ian , DOUGHTY, Victoria, Alexandra , OAKLEY, Paul, Joseph , QUDDUS, Abdul , TEALL, Martin, Richard , WRIGLEY, Jonathan, David
发明人： BEHER, Dirk , BETTATI, Michela , CHECKSFIELD, Graham, David , CHURCHER, Ian , DOUGHTY, Victoria, Alexandra , OAKLEY, Paul, Joseph , QUDDUS, Abdul , TEALL, Martin, Richard , WRIGLEY, Jonathan, David
IPC分类号： A61K31/4439
CPC分类号： C07D401/04 , A61K31/403 , A61K31/4439 , C07D209/86 , C07D209/88 , C07D209/96 , C07D409/04
摘要： Compounds of formula (I): are useful in the treatment of diseases associated with deposition of β-amyloid in the brain.
摘要翻译：式（I）化合物：可用于治疗与脑中β-淀粉样蛋白沉积相关的疾病。

6. 发明申请

WO1997018206A1 MORPHOLINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS 审中-公开
标题翻译：吗啉衍生物及其用作治疗药物
公开(公告)号：WO1997018206A1
公开(公告)日：1997-05-22
申请号：PCT/GB1996002766
申请日：1996-11-13
申请人： MERCK SHARP & DOHME LIMITED , SWAIN, Christopher, John , TEALL, Martin, Richard , WILLIAMS, Brian, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D413/04
CPC分类号： C07D413/04 , C07D417/04
摘要： The present invention relates to compounds of formula (I) wherein X is a 5- or 6-membered C-linked heteroaromatic ring containing 1 to 4 nitrogen atoms and optionally containing in the ring one oxygen or sulphur atom; Y is a group of the formula -(CH2)nNR R , or a methylene- or ethylene-linked imidazolyl group; Z is hydrogen or C1-4alkyl optionally substituted by a hydroxy group; R , R , R , R , R , R and R are a variety of substituents; R is hydrogen, C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, phenyl, or C2-4alkyl substituted by C1-4alkoxy or hydroxy; R is hydrogen, C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, phenyl, or C2-4alkyl substituted by one or two substituents selected from C1-4alkoxy, hydroxy or a 4-, 5- or 6-membered heteroaliphatic ring containing one or two heteroatoms selected from N, O and S; or R and R , together with the nitrogen atom to which they are attached, form a saturated or partially saturated heterocyclic ring or a non-aromatic azabicyclic ring system; and n is zero, 1 or 2; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of pain, inflammation, migraine, emesis and postherapeutic neuralgia.
摘要翻译：本发明涉及式（I）化合物，其中X是含有1至4个氮原子并且任选地在环中含有一个氧或硫原子的5-或6-元C-连接的杂芳环; Y是式 - （CH 2）n NR 6 R 7或亚甲基或亚乙基连接的咪唑基的基团; Z是氢或任选被羟基取代的C 1-4烷基; R 1，R 2，R 3，R 4，R 5，R 9a和R 9b是各种取代基; R 6是氢，C 1-6烷基，C 3-7环烷基，C 3-7环烷基C 1-4烷基，苯基或被C 1-4烷氧基或羟基取代的C 2-4烷基; R 7是氢，C 1-6烷基，C 3-7环烷基，C 3-7环烷基C 1-4烷基，苯基或被一个或两个选自C 1-4烷氧基，羟基或4-，5-或6-烷氧基的取代基取代的C 2-4烷基，含有一个或两个选自N，O和S的杂原子的6-元杂脂族环; 或R 6和R 7与它们所连接的氮原子一起形成饱和或部分饱和的杂环或非芳族氮杂双环体系; n为零，1或2; 或其药学上可接受的盐。该化合物特别用于治疗或预防疼痛，炎症，偏头痛，呕吐和治疗后神经痛。

7. 发明申请

WO1993001160A1 AROMATIC COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USE IN THERAPY 审中-公开
标题翻译：芳香族化合物，含有它们的药物组合物及其在治疗中的用途
公开(公告)号：WO1993001160A1
公开(公告)日：1993-01-21
申请号：PCT/GB1992001213
申请日：1992-07-03
申请人： MERCK SHARP & DOHME LIMITED , SWAIN, Christopher, John , TEALL, Martin, Richard , WILLIAMS, Brian, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07C217/48
CPC分类号： C07D295/185 , A61K38/00 , C07C211/29 , C07C217/48 , C07C217/64 , C07C229/14 , C07C229/36 , C07C233/18 , C07C233/22 , C07C233/73 , C07C237/06 , C07C237/08 , C07C237/20 , C07C255/13 , C07C255/54 , C07C271/16 , C07C271/20 , C07C271/22 , C07C275/10 , C07C275/24 , C07C275/28 , C07C311/04 , C07C2601/02 , C07D207/28 , C07D241/08 , C07D295/092 , C07K5/06026 , Y10S514/886
摘要： Compounds of formula (I), and salts and prodrugs thereof, wherein Q is R?9CR10R11¿ or CH¿2?R?9CR10R11¿ where R9 is H or OH and R?10 and R11¿ are optionally substituted phenyl, optionally substituted benzyl, C¿5-7?cycloalkyl or (C5-7cycloalkyl)methyl; R?1 and R2¿ are H, optionally substituted C¿1-6? alkyl, optionally substituted phenyl(C1-4 alkyl), C2-6 alkenyl, C2-6 alkynyl, COR?a, COORa¿, COC¿1-6?alkylhalo, COC1-6alkylNR?aRb, CONR12C¿1-6alkylCONR?aRb, CONRaRb¿, or SO¿2?R?a, or R1 and R2¿ together form a chain (CH¿2?)q optionally substituted by oxo where one methylene group may optionally be replaced by O or NR?x; R3¿ is H, C¿1-6? alkyl or C2-6alkenyl; R?4¿ is optionally substituted phenyl(C¿1-3? alkyl); X and Y are H, or X and Y together are =O; and Z is O, S, or NR?7¿; are tachykinin antagonists. They and compositions thereof are useful in therapy.
摘要翻译：由式（I）所示的化合物及其盐和前药，其中Q代表R9CR10R11 CH2R9CR10R11或其中R9是H或OH，R10和R11是任选取代的苯基，任选取代的苄基，环烷基或C 1-7环烷基C5- 7甲基; R1和R2是H，任选取代的C 1-6烷基，任选取代的苯基C 1-4烷基，C 2-6烯基，C 2-6炔基，科拉，COORa，COC 1-6烷基卤素，COC 1-6烷基NRARB，CONR12C1-6alkyleCONRaRb， CONRaRb，或SO2Ra，或者R1和R2一起形成一个链（CH 2）●任选地被氧取代，其中一个亚甲基可任选地被O或N rx个取代; R3是H，C1-6烷基或C2-6链烯基; R4代表任选取代的C1-3烷基苯基; X和Y是H，或者X和Y一起是= O; Z是O，S或NR7。所述化合物是速激肽的拮抗剂，并且含有它们的药物组合物具有治疗用途。

8. 发明申请

WO2003048132A1 IMIDAZOPYRIDINES, PYRIMIDINES AND TRIAZINES FOR ENHANCING COGNITION AS GABA-A ALPHA 5 RECEPTOR SUBTYPE LIGANDS 审中-公开
标题翻译：用于增强作为GABA-ALPHA 5受体亚型配体的认知的咪唑吡啶，嘧啶和三嗪
公开(公告)号：WO2003048132A1
公开(公告)日：2003-06-12
申请号：PCT/GB2002/005337
申请日：2002-11-27
申请人： MERCK SHARP & DOHME LIMITED , BETTATI, Michela , CHAMBERS, Mark, Stuart , HUMPHRIES, Alexander, Charles , JONES, Philip , LEWIS, Richard, Thomas , MAXEY, Robert, James , SZEKERES, Helen, Jane , TEALL, Martin, Richard
发明人： BETTATI, Michela , CHAMBERS, Mark, Stuart , HUMPHRIES, Alexander, Charles , JONES, Philip , LEWIS, Richard, Thomas , MAXEY, Robert, James , SZEKERES, Helen, Jane , TEALL, Martin, Richard
IPC分类号： C07D235/04
CPC分类号： C07D471/04 , C07D487/04
摘要： The present invention provides a pharmaceutical composition providing a compound of formula I or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable excipient: (I), in which: X and Y independently represent CH or N, with the proviso that if X is CH then Y is also CH; R 1 represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, nitro, -OR a , -SR a , -SOR a , -SO 2 R a , -SO 2 NR a R b , -NR a R b , -NR a COR b , -NR a CO 2 R b , -COR a , -CO 2 R a , -CONR a R b or CR a =NOR b ; R a and R b independently represent hydrogen, hydrocarbon or a heterocyclic group; V and W are independently selected from H, halogen, C -1-6 alkyl, OH and C -1-6 alkoxy; Z represents H, halogen, CN, NO 2 , CF 3 , OCF 3 , CF 2 H, SCF 3 , R 2 , OR 3 , SR 3 , (CH 2 )pN(R 3 ) 2 , O(CH 2 )pN(R 3 ) 2 , SO 2 R 2 , SO 2 N(R 3 ) 2 , COR 4 , CO 2 R 3 , CON(R 3 ) 2 , NHCOR 4 , NR 1 (CH 2 ) n heteroaryl or O(CH 2 ) n heteroaryl the heteroaryl is optionally substituted by one, two or three groups chosen from C 1-6 alkyl, benzyl, (CH 2 )pN(R 3 ) 2 , halogen and CF 3 , R 1 is C 1-6 alkyl, where n is 1 or 2 and p is 0, 1 or 2; with the proviso that at least one of V, W and Z is other than H; R 2 represents C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or heteroaryl, any of which may bear a substituent selected from halogen, CN, NO 2 , CF 3 , OCF 3 , CF 2 H, SCF 3 , OH, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, amino, C 1-4 alkylamino, or di(C 1-4 alkyl)amino; R 3 represents H or R 2 ; or two R 3 groups bonded to the same nitrogen atom may complete a 5-7 membered nonaromatic heterocyclic ring; and R 4 represents R 3 or heteroaryl; the compounds are ligands for GABA-A receptors containing the alpha 5 subtype and thus are useful for enhancing cognition in individuals suffering from conditions such as Alzheimer's Disease.
摘要翻译：本发明提供在药学上可接受的赋形剂中提供式I化合物或其药学上可接受的盐的药物组合物：其中：X和Y独立地表示CH或N，条件是如果X是CH则 Y也是CH; R 1表示氢，烃，杂环基，卤素，氰基，三氟甲基，硝基，-OR a，-SR a，-SOR a，-SO 2 R a，-SO 2 NR a R b，-NR a R b，-NR a COR b，-NR a CO 2 R b，-COR a，-CO 2 R a，-CONR， a> R 或CR = NOR ; R a和R b独立地表示氢，烃或杂环基; V和W独立地选自H，卤素，C 1-6烷基，OH和C 1-6烷氧基; Z表示H，卤素，CN，NO 2，CF 3，OCF 3，CF 2 H，SCF 3，R 2，OR 3，SR 3，（CH 2）pN（R 3）2，O（CH 2）p N （R 3）2，SO 2 R 2，SO 2 N（R 3）2，COR 4，CO 2 R 3，CON（R 3）2，NHCOR 4，NR 1 （CH2）杂芳基或O（CH2）杂芳基，杂芳基任选被一个，两个或三个选自C 1-6烷基，苄基，（CH 2）pN（R 3）2，卤素和CF 3，R 1，是C 1-6烷基，其中n是1或2，p是0,1或2; 条件是V，W和Z中的至少一个不是H; R 2表示C 1-6烷基，C 3-6环烷基，C 3-6环烷基C 1-4烷基，C 2-6烯基，C 2-6炔基或杂芳基，其中任何一个可以带有选自卤素，CN，NO 2，CF 3，OCF 3，CF 2 H，SCF 3，OH ，C 1-4烷氧基，C 1-4烷氧基羰基，氨基，C 1-4烷基氨基或二（C 1-4烷基）氨基; R 3表示H或R 2; 或两个与相同氮原子键合的R 3基团可以完成5-7元非芳族杂环; 并且R 4表示R 3或杂芳基; 该化合物是含有α5亚型的GABA-A受体的配体，因此可用于增强患有诸如阿尔茨海默氏病等疾病的个体的认知。

9. 发明申请

WO2002081435A1 SULPHONES WHICH MODULATE THE ACTION OF GAMMA SECRETASE 审中-公开
标题翻译：调节伽马秘密行动的磺胺
公开(公告)号：WO2002081435A1
公开(公告)日：2002-10-17
申请号：PCT/GB2001/003741
申请日：2001-08-21
申请人： MERCK SHARP & DOHME LIMITED , CASTRO PINEIRO, Jose, Luis , CHURCHER, Ian , DINNELL, Kevin , HARRISON, Timothy , KERRAD, Sonia , NADIN, Alan, John , OAKLEY, Paul, Joseph , OWENS, Andrew, Pate , SHAW, Duncan, Edward , TEALL, Martin, Richard , WILLIAMS, Brian, John , WILLIAMS, Susannah
发明人： CASTRO PINEIRO, Jose, Luis , CHURCHER, Ian , DINNELL, Kevin , HARRISON, Timothy , KERRAD, Sonia , NADIN, Alan, John , OAKLEY, Paul, Joseph , OWENS, Andrew, Pate , SHAW, Duncan, Edward , TEALL, Martin, Richard , WILLIAMS, Brian, John , WILLIAMS, Susannah
IPC分类号： C07C317/46
CPC分类号： C07D207/27 , C07C317/14 , C07C317/20 , C07C317/24 , C07C317/30 , C07C317/46 , C07C2601/02 , C07C2601/04 , C07C2601/08 , C07C2601/10 , C07C2601/14 , C07C2601/16 , C07C2601/18 , C07D207/12 , C07D207/404 , C07D211/18 , C07D211/42 , C07D211/46 , C07D211/54 , C07D211/60 , C07D211/62 , C07D213/40 , C07D213/64 , C07D213/65 , C07D231/12 , C07D233/32 , C07D233/40 , C07D233/56 , C07D233/64 , C07D241/18 , C07D249/04 , C07D249/08 , C07D249/12 , C07D257/04 , C07D263/38 , C07D263/44 , C07D271/06 , C07D277/26 , C07D285/12 , C07D295/088 , C07D295/096 , C07D295/182 , C07D307/52 , C07D309/08 , C07D309/10 , C07D317/48 , C07D317/72 , C07D491/10 , C07F7/0812
摘要： Novel sulphones of Formula I are disclosed: wherein A completes a 4-7 membered ring optionally comprising up to two heteroatoms. The compounds modulate the action of g-secretase and are therefore useful in the treatment or prevention of Alzheimer's disease.
摘要翻译：公开了式I的新型砜：其中A完成任选包含最多两个杂原子的4-7元环。该化合物调节g-分泌酶的作用，因此可用于治疗或预防阿尔茨海默氏病。

10. 发明申请

WO1995018124A1 SUBSTITUTED MORPHOLINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS 审中-公开
标题翻译：取代的吗啉衍生物及其作为治疗剂的用途
公开(公告)号：WO1995018124A1
公开(公告)日：1995-07-06
申请号：PCT/GB1994002819
申请日：1994-12-23
申请人： MERCK SHARP & DOHME LIMITED , BAKER, Raymond , HARRISON, Timothy , MACLEOD, Angus, Murray , OWENS, Andrew, Pate , SEWARD, Eileen, Mary , SWAIN, Christopher, John , TEALL, Martin, Richard
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D413/06
CPC分类号： C07D413/06 , C07D413/14 , C07F9/6533 , C07F9/65583
摘要： The present invention relates to compounds of formula (I), wherein R is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, CF3, NO2, CN, SR , SOR , SO2R , CO2R , CONR R , C2-6 alkenyl, C2-6 alkynyl or C1-4 alkyl substituted by C1-4 alkoxy, where R and R are hydrogen or C1-4 alkyl; R is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy substituted by C1-4 alkoxy or CF3; R is hydrogen, halogen or CF3; R is selected from the definitions of R ; R is selected from the definitions of R ; R is a 5-membered or 6-membered heterocyclic ring containing 2 or 3 nitrogen atoms optionally substituted by =O, =S or a C1-4 alkyl group, and optionally substituted by an aminoalkyl group; R and R are hydrogen or C1-4 alkyl, or R and R are joined to form a C5-7 ring; X is C1-4 alkylene optionally substituted by oxo; and Y is a C1-4 alkyl group optionally substituted by hydroxyl; with the proviso that if Y is C1-4 alkyl, R is substituted at least by an aminoalkyl group; and pharmaceutically acceptable salts and prodrugs thereof. The compounds are of particular use in the treatment of pain, inflammation, migraine and emesis.
摘要翻译：本发明涉及式（I）化合物，其中R 1是氢，卤素，C 1-6烷基，C 1-6烷氧基，CF 3，NO 2，CN，SR a，SOR a，SO 2 R， α，CO 2 R a，CONR a R b，C 2-6烯基，C 2-6炔基或被C 1-4烷氧基取代的C 1-4烷基，其中R a和R b是氢或C 1-4烷基; R 2是氢，卤素，C 1-6烷基，被C 1-4烷氧基或CF 3取代的C 1-6烷氧基; R 3是氢，卤素或CF 3; R 4选自R 1的定义; R 5选自R 2的定义; R 6是含有2或3个氮原子的5元或6元杂环，其任选被= O，= S或C 1-4烷基取代，并且任选被氨基烷基取代; R 9a和R 9b是氢或C 1-4烷基，或R 9a和R 9b连接形成C5-7环; X是任选被氧代取代的C 1-4亚烷基; Y是任选被羟基取代的C 1-4烷基; 条件是如果Y是C 1-4烷基，则R 6至少被氨基烷基取代; 及其药学上可接受的盐和前药。该化合物特别用于治疗疼痛，炎症，偏头痛和呕吐。

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