Claims
- 1. A compound of formula I, or a salt or prodrug thereof: ##STR22## wherein Z represents --SO2NR.sup.5 R.sup.6 or a group of formula (Zb): ##STR23## in which the asterisk * denotes a chiral centre; or Z represents an optionally substituted imidazol-1-yl; 1,2,4-triazol-1-yl; or 1,2,4-triazol-4-yl moiety, the optional substituents being one or more groups selected from methyl, ethyl, benzyl, and amino;
- X represents oxygen;
- Y represents oxygen;
- E represents a chemical bond or a methylene or ethylene linkage;
- Q represents a straight propylene chain, optionally substituted in any position by one or more substituents selected from fluoro and hydroxy, or by an oxo moiety;
- T represents CH;
- U represents C-R.sup.2 ;
- V represents N-R.sup.3 ;
- -F-G- represents --CM--CH.sub.2 -- or --C.dbd.CH--;
- M represents hydrogen, halogen or C.sub.1-6 alkoxy;
- R.sup.1 represents C.sub.3-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-6 alkynyl, C.sub.3-7 cycloalkyl(C.sub.1-6)alkyl, aryl(C.sub.1-6)alkyl or heteroaryl(C.sub.1-6)alkyl, any of which groups may be optionally substituted;
- R.sup.2 and R.sup.3 both represent hydrogen;
- R.sup.4 represents hydrogen or methyl; and
- R.sup.5 and R.sup.6 independently represent hydrogen or methyl.
- 2. A compound as claimed in claim 1 wherein Q represents a straight propylene chain, optionally substituted in any position by one or more substituents selected from fluoro and hydroxy.
- 3. A compound as claimed in claim 1 represented by formula IIA, and salts and prodrugs thereof: ##STR24## wherein m is zero, 1; or 2;
- p is zero, 1 or 2;
- Q.sup.1 represents a straight propylene chain, optionally substituted in any position by one or more substituents selected from fluoro and hydroxy;
- T represents CH;
- A represents nitrogen or CH;
- B represents nitrogen or C-R.sup.8, with the proviso that both A and B cannot simultaneously represent nitrogen;
- R.sup.7 and R.sup.8 independently represent hydrogen, methyl, ethyl, benzyl, or amino;
- W represents tert-butyl, cyclohexyl, phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or pyridazinyl, any of which groups may be unsubstituted or substituted by one or more groups selected from halogen, cyano, trifluoromethyl, triazolyl, tetrazolyl, C.sub.1-6 alkyl-tetrazolyl, C.sub.1-6 alkoxy, C.sub.2-6 alkylcarbonyl, amino, C.sub.1-6 alkylamino, di(C.sub.1-6)alkylamino, di(C.sub.1-6)alkylaminomethyl, C.sub.2-6 alkylcarbonylamino, C.sub.1-6 alkylsulphonylamino, aminocarbonylamino, C.sub.1-6 alkylaminocarbonyl, arninosulphonyl and C.sub.1-6 alkylaminosulphonylmethyl; and
- R.sub.10 represents hydrogen, C.sub.1-3 alkyl, hydroxy(C.sub.1-3)alkyl or C.sub.1-6 alkylaminocarbonyl.
- 4. A compound of formula IIB, and salts and prodrugs thereof: ##STR25## wherein m is zero, 1 or 2;
- p is zero, 1 or 2;
- Q.sup.1 represents a straight propylene chain, optionally substituted in any position by one or more substituents selected from fluoro and hydroxy;
- T represents CH;
- R.sup.5 and R.sup.6 represent hydrogen or methyl;
- W represents tert-butyl, cyclohexyl, phenyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl or pyridazinyl, any of which groups may be unsubstituted or substituted by one or more groups selected from halogen, cyano, trifluoromethyl, triazolyl, tetrazolyl, C.sub.1-6 alkyl-tetrazolyl, C.sub.1-6 alkoxy, C.sub.2-6 alkylcarbonyl, amino, C.sub.1-6 alkylamino, di(C.sub.1-6)alkylamino, di(C.sub.1-6)alkylaminomethyl, C.sub.2-6 alkylcarbonylamino, C.sub.1-6 alkylsulphonylamino, aminocarbonylamino, C.sub.1-6 alkylaminocarbonyl, aminosulphonyl and C.sub.1-6 alkylaminosulphonylmethyl; and
- R.sub.10 represents hydrogen, C.sub.1-3 akyl hydroxy(C.sub.1-3)alkyl or C.sub.1-6 alkylaminocarbonyl.
- 5. A compound of formula IIC, and salts and prodrugs thereof: ##STR26## wherein the asterisk * denotes a chiral centre; m, p, Q.sup.1, T, W and R.sup.10 are as defined in claim 4;
- R.sup.4 represents hydrogen or methyl; and
- Y represents oxygen.
- 6. A compound as claimed in claim 3 wherein W represents tert-butyl, cyclohexyl or a group of formula (Wa), (Wb) or (Wc): ##STR27## in which W.sup.1 represents CH or nitrogen;
- W.sup.2 represents oxygen, sulphur, NH or N-methyl; and
- R.sup.9 represents hydrogen, halogen, cyano, trifluoromethyl, triazolyl, tetrazolyl, C.sub.1-6 alkyl-tetrazolyl, C.sub.1-6 alkoxy, C.sub.2-6 alkylcarbonyl, amino, C.sub.1-6 alkylamino, di(C.sub.1-6)alkylamino, di(.sub.1-6)alkylaminomethyl, C.sub.2-6 alkylcarbonylamino, C.sub.1-6 alkylsulphonylamino, aminocarbonylamino, C.sub.1-6 alkylaminocarbonyl, aminosulphonyl or C.sub.1-6 alkylaminosulphonylmethyl.
- 7. A compound selected from:
- 1-benzyl-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-(3,3-dimethylbutyl)-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-(2-phenylethyl)-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-cyclohexylmethyl-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-(3-phenylpropyl)-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-[2-(3-fluorophenyl)ethyl]-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-[2-(4-trifluoromethylphenyl)ethyl]-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-[2-(3,4-difluorophenyl)ethyl]-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- N-methyl-2-phenyl-2-[4-(3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl)piperidin-1-yl]acetamide;
- 1-(2-oxo-2-phenylethyl)-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-(2-phenylpropyl)-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-(2-hydroxy-1-phenylethyl)-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- 1-[2-(2-fluorophenyl)ethyl] -4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;
- and salts and prodrugs thereof.
- 8. A compound selected from:
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(2-chlorophenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(2-trifluoromethylphenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(4-chlorophenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(4-methoxyphenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(2,6-dichlorophenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(3-methoxyphenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(2-methoxyphenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(3-chlorophenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(3-aminosulphonylphenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(pyrimidin-2-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(thiazol-2-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(pyrazin-2-yl)propyl]piperazine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(imidazol-1-yl)propyl]piperazine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(pyrazol-1-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(pyridin-2-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(pyridin-3-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(pyridin-4-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(pyridazin-3-yl)propyl]piperidine;
- 4-fluoro-4-[3-(5-(1, 2, 4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(pyridin-3-yl)propyl]piperidine;
- 4-[.sup.3 -(.sup.5 -(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(thien-3-yl)propyl]piperidine;
- 4-[.sup.3 -(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(2-methoxypyridin-3-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(4-methoxypyridin-3-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[(R)-2-(pyridin-3-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[(S)-2-(pyridin-3-yl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[(S)-(2-phenylpropyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[(R)-2-phenylpropyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(2-fluorophenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(3-fluorophenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(4-fluorophenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[2-(2-chloro-5-(trifluoromethyl)phenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-[(S)-2-(4-fluorophenyl)propyl]piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-(2-hydroxy-2-phenylpropyl)piperidine;
- 4-[3-(5-(N-(methyl)aminosulphonylmethyl)-1 H-indol-3-yl)propyl]-1-(2-phenylpropyl)piperidine;
- 4-[3-(5-(N-(methyl)aminosulphonylethyl)-1H-indol-3-yl)propyl]-1-(2-phenylpropyl)piperidine;
- 4-[3-(5-(2-ethylimidazol-1-yl)-1H-indol-3-yl)propyl]-1-(2-phenylpropyl)piperidine;
- 4-[3-(5-((S)-2-oxo-1,3-oxazolidin-4-ylmethyl)-1H-indol-3-yl)propyl]-1-(2-phenylpropyl)piperidine;
- 4-fluoro-4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-(2-phenylpropyl)piperidine;
- 4-[2-fluoro-3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-1-(2-phenylpropyl)piperidine;
- 4-[.sup.3 -(.sup.5 -(1,2,4-triazol-4-yl)-1H-indol-3-yl)-2-hydroxypropyl]-1-(2-phenylpropyl)piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)-2-oxopropyl]-1-(2-phenylpropyl)piperidine;
- 4-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)-1-hydroxypropyl]-1-(2-phenylpropyl)piperidine;
- and salts and prodrugs thereof.
- 9. A pharmaceutical composition comprising a compound of formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof or a prodrug thereof in association with a pharmaceutically acceptable carrier.
- 10. A method for the treatment of clinical conditions for which an agonist of 5-HT.sub.1D receptors selective for the 5-HT.sub.1D.sbsb..alpha. subtype thereof is indicated, which method comprises administering to a patient in need of such treatment an effective amount of a compound of formula I as defined in claim 1, or a pharmaceutically acceptable salt thereof or a prodrug thereof.
- 11. A compound as claimed in claim 4 wherein W represents tert-butyl, cyclohexyl or a group of formula (Wa), (Wb) or (Wc): ##STR28## in which W.sup.1 represents CH or nitrogen;
- W.sup.2 represents oxygen, sulphur, NH or N-methyl; and
- R.sup.9 represents hydrogen, halogen, cyano, trofluoromethyl, triazolyl, tetrazolyl, C.sub.1-6 alkyl-tetrazolyl, C.sub.1-6 alkoxy, C.sub.2-6 alkylcarbonyl, amino, C.sub.1-6 alkylamino, di(C.sub.1-6)alkylamino, di(C.sub.1-6)alkylaminomethyl, C.sub.2-6 alkylcarbonylamino, C.sub.1-6 alkylsulphonylamino, aminocarbonylamino, C.sub.1-6 alkylaminocarbonyl, aminosulphonyl or C.sub.1-6 alkylaminosulphonylmethyl.
- 12. A compound as claimed in claim 5 wherein W represents tert-butyl, cyclohexyl or a group of formula (Wa), (Wb) or (Wc): ##STR29## in which W.sup.1 represents CH or nitrogen;
- W.sup.2 represents oxygen, sulphur, NH or N-methyl; and
- W9 repreents hydrogen, halogen, cyano, trifluoromethyl, triazolyl, tetrazolyl, C.sub.1-6 alkyl-tetrazolyl, C.sub.1-6 alkoxy, C.sub.2-6 alkylcarbonyl, amino, C.sub.1-6 alkylamino, di(C.sub.1-6)alkylamino, di(C.sub.1-6)alkylaminomethyl, C.sub.2-6 alkylcarbonylamino, C.sub.1-6 alkylsulphonylamino, aminocarbonylamino, C.sub.1-6 alkylaminocarbonyl, aminosulphonyl or C.sub.1-6 alkylaminosulphonylmethyl.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9523583 |
Nov 1995 |
GBX |
|
CROSS-REFERENCE
This application is a 371 of PCT/GB96/02795 filed on Nov. 14, 1996.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/GB96/02795 |
11/14/1996 |
|
|
5/13/1998 |
5/13/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/19073 |
5/29/1997 |
|
|
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5451588 |
Baker et al. |
Sep 1995 |
|
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