SCHOFIELD PAUL (GB)
ASTRAZENECA UK LTD (GB)
BLOCK MICHAEL HOWARD (GB)
SCHOFIELD PAUL (GB)
WO1999055667A1 | 1999-11-04 | |||
WO1997019682A1 | 1997-06-05 | |||
WO2001009120A1 | 2001-02-08 |
EP0783503A1 | 1997-07-16 |
pis 1 or 2; q is 1 or 2 ; and n is 1 or 2; or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
2. A compound of formula (I) according to claim 1 wherein A is Group la or Group lb or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
3. A compound of formula (I) according to claim 1 wherein A is Group le or Group ld or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
4. A compound of formula (I) according to any one of claims 1-3 wherein R, is R4-and R2 is-SO2-Rs or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
5. A compound of formula (1) according to any one of claims 1-4 wherein R4 is quinolinyl, quinazolinyl or 1,2,3,4-tetrahydronaphthyl, optionally substituted by one or more substituents independently selected from halo, amino or C, 4alkyl, wherein the Cl 4alkyl is optionally substituted by 3 substituents independently selected from halo and Cl 4alkoxy or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
6. A compound of formula (I) according to any one of claims 1-5 wherein R4 is optionally substituted by one or more substituents independently selected from chloro, fluoro, methyl, ethyl, trifluoromethyl or amino or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
7. A compound of formula (1) according to any one of claims 1-6 wherein p is 1, q is 1 and n is 1 or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
8. A compound of formula (I) according to any one of claims 1-7 wherein B is a direct bond or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
9. A compound of formula (I) according to any one of claims 1-8 wherein Rs is naphthyl, optionally substituted by one or more substituents independently selected from halo, alkyl, cyano, Cl 4alkoxy, Cl 4alkanoyl and amino or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
10. A compound of formula (I) according to any one of claims 1-9 wherein R3 is hydrogen, benzyl or Cl 4allçyl or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
11. A compound of formula (I) selected from : trans-2- (naphth-1-ylsulphonyl)-7- [ (4-aminoquinazolin-2-yl) aminometllyl] octahydro-2H- pyrido [1, 2-a] pyrazine; trans-1-benzyl-2-(naphth-1-ylsulphonylaminomethyl)-5-[(2-met hylquinolin-4- yl) aminomethyl] piperidine ; trans-2-phenylsulphonylaminomethyl-5-[(2-methylquinolin-4-yl ) aminomethyl] piperidine ; trans-2- (naphth-1-ylsulphonyl)-7- [ (1,2,3,4-tetrahydronaphth-2- yl) methylaminomethyl] octahydro-2H-pyrido [1, 2-a] pyrazine; trans-2- (naphth-1-ylsulphonyl)-7- [ (4-aminoquinazolin-2-yl) aminomethyl] octahydro-2H- pyrido [1, 2-a] pyrazine; and trans-1-benzyl-2- (phenylsulphonylaminomethyl)-5- [ (4-aminoquinazolin-2- yl) aminomethyl] piperidine; or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
12. A compound of formula (I) selected from: trans-1-ethyl-2-(naphth-1-ylsulphonylaminomethyl)-5-[(2-meth ylquiolin-4- yl) aminomethyl] piperidine; trans-2- (naphth-1-ylsulphonyl)-7- [ (2-methyl-7-chloroquinolin-4-yl) aminomethyl] octahydro- 2H-pyrido [1, 2-a] pyrazine ; trans-2-(naphth-1-ylsulphonyl)-7-[(2-methyl-4-fluoroquinolin -4-yl)aminomethyl] octahydro- 2H-pyrido [1,2-a] pyrazine; trans-2-(naphth-1-ylSulphonyl)-7-[(2-methylquinolin-4-yl) aminomethyl] octahydro-2H- pyrido [1, 2-a] pyrazine ; and
trans-1-ethyl-2-phenylsulphonylaminomethyl-5-[(2-methylquino lin-4- yl) aminomethyl] piperidine; or a pharmaceutically-acceptable salt, pro-drug or solvate thereof.
13 A process for preparing a compound of formula (I) wherein Rl, R2, R3, R4, Rs A, B, n, p and q are, unless otherwise specified as defined in claim 1 which comprises: (a) reacting an amine of formula (II), wherein B is a direct bond and R2is selected from <BR> <BR> <BR> <BR> -SOz-R4 or-SOz-Rs<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> H-A-R2 formula (II) with a compound of the formula R, L wherein L is a displaceable group; (b) reacting an amine of formula (III) wherein R, is selected from R4or Rs R-A-H formula (III) with a sulphonyl compound of the formula LR2, wherein L is a displaceable group and R2 is selected from -SO2-R4 or -SO2-R5 ; (c) for a compound of formula (I) wherein A is Group la or Group lb and R3 is other than hydrogen, reacting a group of formula (I) wherein A is Group la or Group lb and R3 is hydrogen, with a group of the formula LR3 wherein L is a displaceable group; (d) for a compound of formula (I) wherein A is Group lc or Group ld and B is carbonyl, reacting an amine of formula (IV) H2N-A'-SO2-R2 formula (IV) wherein A'is selected from Group 1 c'or Group ld' Group1e' Group 1d' with an acid of formula (V)
formula (V) or an activated derivative thereof ; (e) for a compound of formula (I) wherein A is Group lc or Group ld and B is methylene, reacting a compound of formula (I) wherein A is Group lc or Group ld and B is carbonyl with a suitable reducing agent; And thereafter if necessary (i) converting a compound of formula (I) into another compound of formula (I) ; (ii) removing any protecting groups; (iii) forming a pharmaceutically-acceptable salt.
14. The use of a compound of formula (I) or pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12, as a medicament.
15. A pharmaceutical composition which comprises a compound of the formula (I) or a phannaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12, in association with a pharmaceutically-acceptable diluent or carrier.
16. A method of treatment, in a warm-blooded animal, of disorders mediated by the neuropeptide Y5 receptor comprising administering to said wann-blooded animal a therapeutically effective amount of a compound of formula (I) or pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12.
17. The use of a compound of formula (I) or pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12, in the manufacture of a medicament for the treatment of a disorder mediated by the neuropeptide Y5 receptor, in a warm blooded animal.
18. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims
1-12, in admixture with a pharmaceutically-acceptable diluent or carrier for the treatment of a warm-blooded animal, in need of treatment, of disorders mediated by the neuropeptide Y5 receptor.
19. A method of treatment, in a wann-blooded animal, of eating disorders, comprising administering a therapeutically effective amount of a compound of formula (I) or pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12.
20. The use of a compound of formula (I) or pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12, in the manufacture of a medicament for the treatment of eating disorders in a warm-blooded animal.
21. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12, in admixture with a pharmaceutically-acceptable diluent or carrier for the treatment of eating disorders in a warm-blooded animal.
22. The method, use or composition, according to claims 19-21 wherein the eating disorders are obesity and related disorders, bulimia or anorexia, wherein the related disorders are diabetes dyslipidaemia, hypertension and sleep disturbances.
23. A method of promoting weight loss, in a warm-blooded animal, comprising administering a therapeutically effective amount of a compound of formula (I) or pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12.
24. The use of a compound of formula (I) or pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12, in the manufacture of a medicament for promoting weight loss in a warm-blooded animal.
25. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically-acceptable salt, pro-drug or solvate thereof, according to any one of claims 1-12, in admixture with a pharmaceutically-acceptable diluent or carrier for promoting weight loss in a warm-blooded animal.