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US 2004/0176397 A1Published application
(Oxo-Pyrazolo[1,5a]pyrimidin-2-yl)Alkyl-Carboxamides
AssigneeNeurogen Corporation
InventorsGuiying Li, John Peterson, Pamela Albaugh
Life of this patent
Estimating the term…
Abstract
Disclosed are compounds of the formula 1 and the pharmaceutically acceptable salts thereof where the variables R1, R2, A, R4, R5, R6, R6′, n, and W are defined herein. These compounds bind to the benzodiazepine site of GABAA receptors are provided and, therefore can be used to modulate ligand binding to GABAA receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals and livestock animals.
Claims78
A compound of the formula
- 26
- or a pharmaceutically acceptable salt thereof, wherein
- n is 1, 2, or 3;
- 27
- R1 and R2 are independently chosen from hydrogen, halogen, hydroxy, amino, mono- and di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl and C1-C6 alkoxy;
- or
- R1 and R2 together with the atoms with which they are attached form a partially saturated or unsaturated carbocyclic ring of from 3 to 8 carbon atoms, wherein the ring is optionally substituted by up to 5 substituents independently chosen from halogen, hydroxy, amino, mono- and di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl and C1-C6 alkoxy;
- R3, R4 and R5 are independently chosen from hydrogen;
- C1-C6 acyl;
- and C1-C6 alkyl;
- wherein each C1-C6 acyl and C1-C6 alkyl is optionally substituted with up to three substituents independently chosen from halogen, hydroxy, halo(C1-C2)alkyl, halo(C1-C2)alkoxy, methoxy, ethoxy, C3-C7 cycloalkyl, phenyl, pyridyl, and pyrimidyl, wherein each of phenyl, pyridyl, and pyrimidyl is optionally substituted with up to three groups independently selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, hydroxy and amino;
- R6 and R6′ are independently selected at each occurrence from hydrogen and C1-C6 alkyl;
- W is aryl or heteroaryl, each of which is optionally substituted with up to 5 groups independently selected from hydrogen, halogen, hydroxy, amino, mono- or di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl, and C1-C4 alkoxy.
10 more elements
A compound of the formula:
- 29
- or a pharmaceutically acceptable salt thereof, wherein:
- n is 1, 2, or 3;
- R1 and R2 are independently chosen from hydrogen, halogen, hydroxy, amino, mono- and di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl, and C1-C6 alkoxy;
- or
- R1 and R2 together with the atoms with which they are attached form a partially saturated or unsaturated carbocyclic ring of from 3 to 8 carbon atoms, wherein the ring is optionally substituted by up to 5 substituents independently chosen from halogen, hydroxy, amino, mono- and di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl and C1-C6 alkoxy;
- R3, R4 and R5 are independently chosen from (i) hydrogen;
- and (ii) C1-C6 acyl and C1-C6 alkyl, optionally substituted with up to three substituents independently chosen from halogen, hydroxy, halo(C1-C2)alkyl, halo(C1-C2)alkoxy, methoxy, ethoxy, C3-C7 cycloalkyl, phenyl, pyridyl and pyrimidyl, wherein each of phenyl, pyridyl and pyrimidyl is optionally substituted with up to three groups selected independently from halogen, C1-C6 alkyl, C1-C6 alkoxy, hydroxy and amino;
- R6 and R6′ are independently selected at each occurrence from hydrogen and C1-C6 alkyl;
- and
- R10, R11, X, Y and Z are independently selected from hydrogen, halogen, hydroxy, amino, mono- and di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl and C1-C6 alkoxy.
8 more elements
A compound of the formula:
- 30
- or a pharmaceutically acceptable salt thereof, wherein:
- n is 1, 2, or 3;
- R1 and R2 are independently chosen from hydrogen, halogen, hydroxy, amino, mono- and di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl, and C1-C6 alkoxy, or
- R1 and R2 together with the atoms with which they are attached form a partially saturated or unsaturated carbocyclic ring of from 3 to 8 carbon atoms, wherein the ring is optionally substituted by up to 5 substituents independently chosen from halogen, hydroxy, amino, mono- and di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl and C1-C6 alkoxy;
- R3, R4 and R5 are independently chosen from (i) hydrogen;
- and (ii) C1-C6 acyl and C1-C6 alkyl, optionally substituted with up to three substituents independently chosen from halogen, hydroxy, halo(C1-C2)alkyl, halo(C1-C2)alkoxy, methoxy, ethoxy, C3-C7 cycloalkyl, phenyl, pyridyl and pyrimidyl, wherein each of phenyl, pyridyl and pyrimidyl is optionally substituted with up to three groups selected independently from halogen, C1-C6 alkyl, C1-C6 alkoxy, hydroxy and amino;
- R6 and R6′ are independently selected at each occurrence from hydrogen and C1-C6 alkyl;
- and
- R10, R11, X, Y and Z are independently selected from hydrogen, halogen, hydroxy, amino, mono- and di(C1-C6)alkyl amino, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C1-C6 alkyl and C1-C6 alkoxy.
7 more elements
Dependencies are inferred from the claim text.