Dopamine receptor ligands
First Claim
1. A compound of Formula I:
- ##STR30## wherein;
A and B independently are both benzene optionally substituted with 1 or 2 substituents selected independently from hydroxyl, halo, C1-4 alkyl, amino, nitro, cyano, halo-substituted C1-4 alkyl, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkoxycarbonyl, C1-4 acyl, halo-substituted C1-4 acyl, cyclo-C1-7 alkyl, thio-C1-4 alkylene, C1-4 alkylthio, halo-substituted C1-4 alkylthio, cyanothio, tetrazolyl, N-piperidinyl, N-piperazinyl, N-morpholinyl, acetamido, C1-4 alkylsulfonyl, halosulfonyl, halo-substituted C1-4 alkylsulfonyl, C1-4 alkylsulfoxyl, sulfonamido, C1-4 alkylseleno, and OSO3 H;
X1 is selected from, O, S, SOs and SO;
X2 - - - is N═
,Y is selected from CH and N;
R1 represent C1-4 alkyl;
n is 0, 1 or 2;
q is 1 or 2;
R2 is C1-6 alkylene optionally incorporating an intervening or terminating heteroatom selected from N, O and S;
D is cyclohexane or benzene andE is a saturated or unsaturated 5- or 6-membered heterocycle incorporating 1, 2 or 3 heteroatoms selected from O, N, and S, wherein E is optionally substituted with 1 or 2 substituents selected from halogen, C1-4 alkyl and halogen-substituted C1-4 alkyl;
and acid addition salts, solvates or hydrates thereof.
1 Assignment
0 Petitions
Accused Products
Abstract
Described herein are D4 receptor-selective compounds of the general formula: ##STR1## wherein: A and B are independently selected, optionally substituted, saturated or unsaturated 5- or 6-membered, homo- or heterocyclic rings;
X1 is selected from CH2, O, NH, S, C═O, CH--OH, CH--N(C1-4 alkyl)2, C═CHCl, C═CHCN, N-C1-4 alkyl, N-acetyl, SO2 and SO;
X2 -- is selected from N═, CH2 --, CH═, C(O)--, O--, and S--;
R1 represents C1-4 alkyl;
Y is selected from CH and N;
n is 0, 1 or 2;
q is 1 or 2;
R2 is C1-6 alkyl optionally incorporating a heteroatom selected from N, O and S;
D is cyclohexane or benzene; and
E is a saturated or unsaturated 5- or 6-membered heterocycle incorporating 1, 2 or 3 heteroatoms selected from O, N, and S, wherein E is optionally substituted with 1 or 2 substituents selected from halogen, C1-4 alkyl and halogen-substituted C1-4 alkyl;
and acid addition salts, solvates and hydrates thereof. Their use as ligands for dopamine receptor identification and in a drug screening program, and as pharmaceuticals to treat indications in which the D4 receptor is implicated, such as schizophrenia, is also described.
21 Citations
29 Claims
-
1. A compound of Formula I:
- ##STR30## wherein;
A and B independently are both benzene optionally substituted with 1 or 2 substituents selected independently from hydroxyl, halo, C1-4 alkyl, amino, nitro, cyano, halo-substituted C1-4 alkyl, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkoxycarbonyl, C1-4 acyl, halo-substituted C1-4 acyl, cyclo-C1-7 alkyl, thio-C1-4 alkylene, C1-4 alkylthio, halo-substituted C1-4 alkylthio, cyanothio, tetrazolyl, N-piperidinyl, N-piperazinyl, N-morpholinyl, acetamido, C1-4 alkylsulfonyl, halosulfonyl, halo-substituted C1-4 alkylsulfonyl, C1-4 alkylsulfoxyl, sulfonamido, C1-4 alkylseleno, and OSO3 H;X1 is selected from, O, S, SOs and SO; X2 - - - is N═
,Y is selected from CH and N; R1 represent C1-4 alkyl; n is 0, 1 or 2; q is 1 or 2; R2 is C1-6 alkylene optionally incorporating an intervening or terminating heteroatom selected from N, O and S; D is cyclohexane or benzene and E is a saturated or unsaturated 5- or 6-membered heterocycle incorporating 1, 2 or 3 heteroatoms selected from O, N, and S, wherein E is optionally substituted with 1 or 2 substituents selected from halogen, C1-4 alkyl and halogen-substituted C1-4 alkyl; and acid addition salts, solvates or hydrates thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29)
- ##STR30## wherein;
-
21. The compound 8-chloro-11-(4-piperonyl-1-piperazinyl)-dibenz[b,f][1,4]oxazepine.
Specification
-
- Resources
-
Current AssigneeNPS Pharmaceuticals Incorporated (Shire plc)
-
Original AssigneeAllelix Biopharmaceuticals, Inc. (NPS Allelix Corp.)
-
InventorsTehim, Ashok, Fu, Jian-Min, Rakhit, Sumanas
-
Primary Examiner(s)Datlow, Philip I.
-
Application NumberUS08/355,297Time in Patent Office589 DaysField of Search540/547, 540/551, 514/211US Class Current514/211.13CPC Class CodesA61P 25/18 Antipsychotics, i.e. neurol...A61P 25/20 Hypnotics; SedativesC07D 405/12 linked by a chain containin...C07D 409/12 linked by a chain containin...C07D 413/12 linked by a chain containin...C07D 417/12 linked by a chain containin...
