CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE
Abstract
The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I):or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from:and ring B, n, R1, R2, R2A, R3, and R3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild congnitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.
Claims
exact text as granted — not AI-modified1 - 30 . (canceled)
31 . A pharmaceutical composition comprising:
(i) a compound having the formula (I):
or a stereoisomer thereof, or a pharmaceutically acceptable salt of said compound or said stereoisomer, wherein:
ring A is a moiety selected from:
wherein:
R 2 is selected from H, cyclopropyl, —(C 1 -C 4 )alkyl, —(C 1 -C 4 )alkyl-OH, —(C 1 -C 4 )alkyl-OCH 3 , —(C 1 -C 4 )haloalkyl, —(C 1 -C 4 )alkyl-O—(C 1 -C 4 )haloalkyl, —CH(CH 3 ) 2 , —CH 2 —O—(C 1 -C 4 )haloalkyl, —CH(CH 3 )—O—(C 1 -C 4 )haloalkyl, —CH 2 —NH—(C 1 -C 4 )haloalkyl, and —CH 2 —N(CH 3 )—(C 1 -C 4 )haloalkyl,
R 2A is selected from H and methyl;
R 3 is selected from H and methyl;
R 3A is selected from H and methyl;
ring B is a moiety selected from the group consisting of phenyl, heteroaryl, —(C 5 -C 6 ) cycloalkyl, and —(C 5 -C 6 ) cycloalkenyl;
n is 0, 1, 2, or 3, provided that the value of n does not exceed the maximum number of substitutable hydrogen atoms on ring B; and
each R 1 (when present) is independently selected from the group consisting of halogen, —CN, —OH, —(C 1 -C 6 ) alkyl, —O—(C 1 -C 6 ) alkyl, —(C 1 -C 6 ) haloalkyl, —O—(C 1 -C 6 ) haloalkyl, cyclopropyl, cyclobutyl, —NH 2 , —NH(C 1 -C 6 )alkyl, —N(C 1 -C 6 alkyl) 2 , —C(O)O(C 1 -C 6 ) alkyl, and phenyl;
(ii) an additional therapeutic agent; and
(iii) a pharmaceutically acceptable carrier.
32 . The composition of claim 31 , wherein the additional therapeutic agent is an acetylcholinesterase inhibitor.
33 . The composition of claim 32 , wherein the acetylcholinesterase inhibitor is donepezil.
34 . The composition of claim 31 , wherein the compound of formula (I) is selected from:
or a stereoisomer thereof, or a pharmaceutically acceptable salt of said compound or said stereoisomer.
35 . The composition of claim 34 , wherein the additional therapeutic agent is an acetylcholinesterase inhibitor.
36 . The composition of claim 35 , wherein the acetylcholinesterase inhibitor is donepezil.
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50 . A method of treating Alzheimer's disease, mild cognitive impairment, schizophrenia, mood disorder, depression, or sleep disorder, said method comprising administering the pharmaceutical composition of claim 31 .
51 . A method of treating Alzheimer's disease, mild cognitive impairment, schizophrenia, mood disorder, depression, or sleep disorder, said method comprising administering the pharmaceutical composition of claim 32 .
52 . A method of treating Alzheimer's disease, mild cognitive impairment, schizophrenia, mood disorder, depression, or sleep disorder, said method comprising administering the pharmaceutical composition of claim 33 .
53 . A method of treating Alzheimer's disease, mild cognitive impairment, schizophrenia, mood disorder, depression, or sleep disorder, said method comprising administering the pharmaceutical composition of claim 34 .
54 . A method of treating Alzheimer's disease, mild cognitive impairment, schizophrenia, mood disorder, depression, or sleep disorder, said method comprising administering the pharmaceutical composition of claim 35 .
55 . A method of treating Alzheimer's disease, mild cognitive impairment, schizophrenia, mood disorder, depression, or sleep disorder, said method comprising administering the pharmaceutical composition of claim 36 .
56 . The method of claim 50 , wherein the treating is for Alzheimer's disease.
57 . The method of claim 52 , wherein the treating is for Alzheimer's disease.
58 . The method of claim 53 , wherein the treating is for Alzheimer's disease.
59 . The method of claim 55 , wherein the treating is for Alzheimer's disease.
60 . The method of claim 50 , wherein the treating is for depression.
61 . The method of claim 53 , wherein the treating is for depression.Join the waitlist — get patent alerts
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