Abstract:
This invention relates to nicotinamide derivatives of formula (I) and to processes for the preparation of, intermediates used in the preparation of, pharmaceutical compositions containing, and the uses of such derivatives: wherein each substituent is defined herein.
Abstract:
A compound of general formula (I), or pharmaceutically acceptable salts, solvates or polymorphs thereof; wherein; R1 and R2, which may be the same or different, are hydrogen, C1-C6alkyl, (CH2)m (C3-C6cycloalkyl) wherein m =0, 1, 2 or 3, or R1 and R2 together with the nitrogen to which they are attached form an azetidine ring; each R3 is independently CF3, OCF3, C1-4alkylthio or C1-C4alkoxy; n is 1, 2 or 3; and R4 and R5, which may be the same or different, are: A—X, wherein A =—CH=CH— or —(CH2)p— where p is 0, 1 or 2; X is hydrogen, F, Cl, Br, I, CONR6R7, SO2NR6R7, SO2NHC(=O)R6, OH, C1-4alkoxy, NR8SO2R9, NO2, NR6R11, CN, CO2R10, CHO, SR10, S(O)R9 or SO2R10; R6, R7, R8 and R10 which may be the same or different, are hydrogen or C1-6alkyl optionally substituted independently by one or more R12; R9 is C1-6 alkyl optionally substituted independently by one or more R12; R11 is hydrogen, C1-6 alkyl optionally substituted independently by one or more R12, C(O)R6, CO2R9, C(O)NHR6 or SO2NR6R7; R12 is F, OH, CO2H, C3-6cycloalkyl, NH2, CONH2, C1-6alkoxy, C1-6alkoxycarbonyl or a 5- or 6-membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, S and O optionally substituted independently by one or more R13; or R6 and R7, together with the nitrogen to which they are attached, form a 4-, 5- or 6-membered heterocyclic ring optionally substituted independently by one or more R13; or a 5- or 6-membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, S and O, optionally substituted independently by one or more R13; wherein R13 is hydroxy, C1-C4alkoxy, F, C1-C6alkyl, haloalkyl, haloalkoxy, —NH2, —NH(C1-C6alkyl) or —N(C1-C6alkyl)2; wherein when R1 and R2 are methyl, R4 and R5 are hydrogen and n is 1, R3is not a —SMe group para to the ether linkage linking rings A and B.
Abstract:
The present invention provides compounds of formula (I) and the pharmaceutically acceptable acid addition salts thereof, wherein X is a direct link or C1-C4 alkylene; and R is C3-C7 cycloalkyl optionally substituted by 1 or 2 substituents each independently selected from fluoro and C3-C7 cycloalkyl: with the proviso that X is not methylene when R is cyclopropyl, together with processes for the preparation of, intermediates used in the preparation of, compositions containing and uses of, such compounds. These compounds are useful as tachykinin antagonists.
Abstract:
Compounds of formula (I) ##STR1## and salts thereof, wherein: R.sup.1 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.4)alky aryl or aryl(C.sub.1 -C.sub.4)alkyl; wherein the C.sub.1 -C.sub.6 alkyl group is optionally substituted by fluorine and the C.sub.3 -C.sub.7 cycloalkyl or C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.4)alkyl group is optionally substituted in the cycloalkyl ring by up to two substituents each independently selected from halo, C.sub.1 -C.sub.4 alkoxy or halo(C.sub.1 -C.sub.4)alkoxy; R.sup.2 is phenyl optionally substituted with one or two halo substituents or is indolyl, thienyl, benzothienyl or naphthyl; R.sup.3 is NH.sub.2,--NR.sup.4 SO.sub.2 (C.sub.1 -C.sub.6 alkyl), --NR.sup.4 SO.sub.2 aryl, --NR.sup.4 SO.sub.2 N(R.sup.4).sub.2, NR.sup.4 CO(C.sub.1 -C.sub.6 alkyl), --NR.sup.4 CO aryl or a group or formula (a) ##STR2## wherein W is O, NR.sup.5, CH(OH), CHCO.sub.2 H, CHN(R.sup.4).sub.2, CHF, CF.sub.2, C.dbd.O or CH.sub.2 ; R.sup.4 is H or C.sub.1 -C.sub.6 alkyl; R.sup.5 is H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.6)alkyl, C.sub.2 -C.sub.6 alkanoyl, C.sub.4 -C.sub.8 cycloalkanoly, C.sub.3 -C.sub.7 cycloalkyl(C.sub.2 -C.sub.6)alkanoyl, aryl CO--, C.sub.1 -C.sub.6 alkylSO.sub.2 --, (R.sup.4).sub.2 NSO.sub.2 --, C.sub.3 -C.sub.7 cycloalkylSO.sub.2 --, C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.6)alkyl-SO.sub.2 --, or arylSO.sub.2 --; X is CH.sub.2 or C.dbd.O; m is 0, 1 or 2 with the proviso that m is not O when W is NR.sup.5, C.dbd.O, or O; and n is an integer of from 1 to 4. These compounds are neurokinin receptor antagonists of utility in the treatment of a variety of medical conditions including urinary incontinence, asthma and related conditions.
Abstract:
This invention relates to biaryl ether derivatives of formula (I) wherein R1, R3, R4, X, W, Y and m are defined in the description, and to compositions containing them and the uses of such derivatives. The compounds of the present invention bind to the enzyme reverse transcriptase and are modulators, especially inhibitors thereof.
Abstract:
Compounds of the formula (I): where X1, A, Ar1, X and R are as defined in the specification, and pharmaceutically-acceptable salts thereof, are new, and are useful as tachykinin inhibitors which act at the NK1, NK2 and NK3 receptors or a combination of two or more thereof.
Abstract:
The invention provides compounds of general formula (I) wherein R1 is H or C1-C6 alkyl; R2 and R3, together with the interconnecting atoms form a 4 to 8-membered saturated ring containing one or two heteroatoms (including the nitrogen to which R2 is attached) wherein a second heteroatom, if present, is selected from oxygen, nitrogen and sulfur, with the proviso that said ring cannot contain two adjacent heteroatoms; Z is CF3, OCF3, C1-C6alkylthio or C1-C6alkoxy; Y is hydrogen, halogen, —ORa, Ra or C1-C6alkylthio, and wherein Ra is C1-C4 alkyl optionally substituted with fluorine atoms; or when Z and Y are attached para and meta to the ether linkage linking rings A and B, Z and Y are linked so that, together with the interconnecting atoms, Z and Y form a fused 5 to 7-membered carbocyclic or heterocyclic ring which may be saturated, unsaturated or aromatic, and wherein when Z and Y form a heterocyclic ring, in addition to carbon atoms, the linkage contains one or two heteroatoms independently selected from oxygen, sulfur and nitrogen; and Z and Y together do not form a fused phenyl ring; R4 and R5, which may be the same or different, are: A—X, wherein A=—CH═CH— or —(CH2)p— where p is 0, 1 or 2; X is hydrogen, F, Cl, Br, I, CONR6R7, SO2NR6R7, SO2NHC(═O)R6, OH, C1-4alkoxy, NR8SO2R9, NO2, NR6R11, CN, CO2R10, CHO, SR10, S(O)R9 or SO2R10; or a 5- or 6-membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, S and O, optionally substituted independently by one or more R13; wherein R13 is hydroxy, C1-C4alkoxy, F, C1-C6alkyl, haloalkyl, haloalkoxy, —NH2, —NH(C1-C6alkyl) or —N(C1-C6alkyl)2.
Abstract translation:本发明提供通式(I)的化合物,其中R 1是H或C 1 -C 6烷基; R 2和R 3连同互连原子形成含有一个或两个杂原子(包括R 2连接的氮)的4至8元饱和环,其中如果存在第二杂原子, 选自氧,氮和硫,条件是所述环不能含有两个相邻的杂原子; Z是CF 3,OCF 3,C 1 -C 6烷硫基或C 1 -C 6烷氧基; Y是氢,卤素,-OR a,R 5c或C 1 -C 6烷硫基,并且其中R 5'是任选被氟原子取代的C 1 -C 4烷基; 或者当Z和Y连接到连接环A和B的醚键时,Z和Y被连接,使得Z和Y连接,使得与互连原子一起形成稠合的5至7元碳环或杂环, 可以是饱和的,不饱和的或芳族的,并且其中当Z和Y形成杂环时,除了碳原子之外,所述键含有一个或两个独立地选自氧,硫和氮的杂原子; 并且Z和Y一起不形成稠合的苯环; R 4和R 5可以相同或不同,为:A-X,其中A = -CH = CH-或 - (CH 2)p - ,其中p为0,1或2; X是氢,F,Cl,Br,I,CONR 6 R 7,SO 2 NR 6 R 7,SO 2 NHC(= O)R 6,OH,C 1-4烷氧基,NR 8 SO 2 R 9,NO 2,NR 6 R 11,CN,CO 2 R 10,CHO,SR 10,S(O)R 9或SO 2 R 10; 或含有1,2或3个选自N,S和O的杂原子的5-或6-元杂环,任选被一个或多个R 13独立地取代; 其中R 13是羟基,C 1 -C 4烷氧基,F,C 1 -C 6烷基,卤代烷基,卤代烷氧基,-NH 2,-NH(C 1 -C 6烷基)或-N(C
Abstract:
The present invention provides compounds of formula (I) and the pharmaceutically acceptable salts thereof. Such compounds and salts are tachykinin antagonists.
Abstract:
Compounds of the formula (I): or a pharmaceutically acceptable salt, prodrug, solvate or polymorph thereof, wherein R, R1, and Z are as defined herein, are useful in treating or preventing a condition for which an NK2 antagonist is efficacious.
Abstract:
The invention relates to compounds of formula (I) for treating for example sexual dysfunction, wherein R1 is optionally substituted C1-6alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C1-6alkoxy, —NR2 R3 or —NR4SO2R5; X is the linkage —(CH2)n— or —(CH2)q—O— (wherein Y is attached to the oxygen); wherein one or more hydrogen atoms in linkage X may be replaced independently by C1-4alkoxy; hydroxy; hydroxy(C1-3alkyl); C3-7cycloalkyl; carbocyclyl; heterocyclyl; or by C1-4alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6 or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R8 groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused optionally substituted 5- or 6-membered carbocyclic or heterocyclyic ring.
Abstract translation:本发明涉及用于治疗例如性功能障碍的式(I)化合物,其中R 1是任选取代的C 1-6烷基,任选取代的碳环基,任选取代的杂环基,氢,C 1-6烷氧基,-NR 2 R 3或-NR 4 SO 2 R 5; X是连接 - (CH 2)n - 或 - (CH 2)q -O-(其中Y连接到氧上); 其中连接X中的一个或多个氢原子可以被C 1-4烷氧基独立地取代; 羟基; 羟基(C 1-3烷基); C 3-7环烷基; 碳环基 杂环基 或被任选被一个或多个氟或苯基取代的C 1-4烷基; n为3,4,5,6或7; q为2,3,4,5或6; Y为苯基或吡啶基,各自可以被取代; 或相邻碳原子上的两个R 8基团与互连碳原子一起可以形成稠合的任选取代的5或6元碳环或杂环基。