US2019142826A1PendingUtilityA1
Imidazo[1,2-a]pyridine derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto
Est. expiryAug 15, 2027(~1 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 9/10A61P 7/02A61P 25/14A61P 25/20A61P 3/10A61P 25/18A61K 9/0019C07D 471/04A61K 31/5377A61K 31/496A61P 11/06A61K 9/0053
59
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
rmidazo[1,2-α]pyridine derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT 2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia, dyssomnia, parasomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, thrombosis, asthma or symptoms thereof, agitation or symptoms thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de Ia Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorders, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to methods for the treatment of 5-HT 2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.
Claims
exact text as granted — not AI-modified1 .- 50 . (canceled)
51 . A process for preparing a compound of Formula (Ia):
wherein:
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonylamino, C 1 -C 6 alkyl, C 1 -C 6 alkylamino, C 2 -C 8 dialkylamino, C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkylsulfonamide, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylureyl, amino, aryl, aryl-C 1 -C 4 -alkylenyl, carbo-C 1 -C 6 -alkoxy, carboxamide, carboxy, cyano, C 3 -C 7 cycloalkyl, C 2 -C 6 dialkylcarboxamide, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 haloalkylsulfonyl, halogen, heteroaryl, heterocyclyl, hydroxyl, nitro and sulfonamide;
R 6 and R 7 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 3 alkyl, aryl, carboxamide, carboxy, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, heteroaryl and heterocyclyl;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 3 alkyl, aryl, carboxamide, C 1 -C 3 alkoxy, carboxy, cyano, C 3 -C 7 cycloalkyl, C 1 -C 3 haloalkyl, halogen and hydroxyl; or
R 8 and R 9 taken together form oxo; or
R 8 and R 9 together with the atom to which they are both bonded form a C 3 -C 7 cycloalkyl ring; and
R 10 , R 11 , R 12 , R 13 and R 14 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonylamino, C 1 -C 6 alkyl, C 1 -C 6 alkylamino, C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonamide, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylureyl, amino, carbo-C 1 -C 6 alkoxy, carboxamide, carboxy, cyano, C 3 -C 6 cycloalkyl, C 3 -C 7 cycloalkylcarbonyl, C 2 -C 8 dialkylamino, C 2 -C 6 dialkylcarboxamide, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 haloalkylsulfonyl, halogen, heteroaryl, heterocyclyl, hydroxyl, nitro, phenyl, sulfonamide and sulfonic acid; wherein said phenyl group is optionally substituted with 1, 2 or 3 halogens;
comprising the coupling of the following phenethyl halide derivative
wherein X is a halogen;
with the following piperazine
52 . The process of claim 51 , further comprising removing a Boc protecting group from the following Boc-piperazine derivative
to obtain a the following piperazine
53 . The process of claim 52 , further comprising the coupling of the imidazopyridine carboxylic acid derivative
wherein W is a halogen;
with the following Boc-piperazine
to obtain the following Boc-piperazine derivative
54 . A process for preparing a compound of Formula (Ia):
wherein:
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonylamino, C 1 -C 6 alkyl, C 1 -C 6 alkylamino, C 2 -C 8 dialkylamino, C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkylsulfonamide, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylureyl, amino, aryl, aryl-C 1 -C 4 -alkylenyl, carbo-C 1 -C 6 -alkoxy, carboxamide, carboxy, cyano, C 3 -C 7 cycloalkyl, C 2 -C 6 dialkylcarboxamide, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 haloalkylsulfonyl, halogen, heteroaryl, heterocyclyl, hydroxyl, nitro and sulfonamide;
R 6 and R 7 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 3 alkyl, aryl, carboxamide, carboxy, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, heteroaryl and heterocyclyl;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 3 alkyl, aryl, carboxamide, C 1 -C 3 alkoxy, carboxy, cyano, C 3 -C 7 cycloalkyl, C 1 -C 3 haloalkyl, halogen and hydroxyl; or
R 8 and R 9 taken together form oxo; or
R 8 and R 9 together with the atom to which they are both bonded form a C 3 -C 7 cycloalkyl ring; and
R 10 , R 11 , R 12 , R 13 and R 14 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonylamino, C 1 -C 6 alkyl, C 1 -C 6 alkylamino, C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonamide, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylureyl, amino, carbo-C 1 -C 6 alkoxy, carboxamide, carboxy, cyano, C 3 -C 6 cycloalkyl, C 3 -C 7 cycloalkylcarbonyl, C 2 -C 8 dialkylamino, C 2 -C 6 dialkylcarboxamide, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 haloalkylsulfonyl, halogen, heteroaryl, heterocyclyl, hydroxyl, nitro, phenyl, sulfonamide and sulfonic acid; wherein said phenyl group is optionally substituted with 1, 2 or 3 halogens;
comprising the coupling of the following piperazine
with the following imidazopyridine carboxylic acid derivative
and wherein W is OH or Cl.
55 . The process of claim 54 , further comprising removing a Boc protecting group from the following Alkylated Boc-piperazine
to obtain a the following piperazine
56 . The process of claim 55 , further comprising the coupling of the following phenethyl halide derivative, wherein X is a halogen
with the following Boc-piperazine
to obtain a the following Alkylated Boc-piperazine
57 . A process for preparing a compound of the following formula:
wherein:
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonylamino, C 1 -C 6 alkyl, C 1 -C 6 alkylamino, C 2 -C 5 dialkylamino, C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkylsulfonamide, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylureyl, amino, aryl, aryl-C 1 -C 4 -alkylenyl, carbo-C 1 -C 6 -alkoxy, carboxamide, carboxy, cyano, C 3 -C 7 cycloalkyl, C 2 -C 6 dialkylcarboxamide, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 haloalkylsulfonyl, halogen, heteroaryl, heterocyclyl, hydroxyl, nitro and sulfonamide;
comprising the demethylation of the following ester
58 . The process of claim 57 , further comprising the reaction of the following 2-aminonicotinic acid derivative
with the following α-haloketone
wherein X is a halogen
to obtain the following ester
59 . The process of claim 58 , further comprising the methylation of the following carboxylic acid
to obtain the following 2-aminonicotinic acid derivative
60 . A process for preparing a compound of the following formula:
wherein:
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonylamino, C 1 -C 6 alkyl, C 1 -C 6 alkylamino, C 2 -C 8 dialkylamino, C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkylsulfonamide, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylureyl, amino, aryl, aryl-C 1 -C 4 -alkylenyl, carbo-C 1 -C 6 -alkoxy, carboxamide, carboxy, cyano, C 3 -C 7 cycloalkyl, C 2 -C 6 dialkylcarboxamide, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 haloalkylsulfonyl, halogen, heteroaryl, heterocyclyl, hydroxyl, nitro and sulfonamide;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 3 alkyl, aryl, carboxamide, C 1 -C 3 alkoxy, carboxy, cyano, C 3 -C 7 cycloalkyl, C 1 -C 3 haloalkyl, halogen and hydroxyl; or
R 8 and R 9 taken together form oxo; or
R 8 and R 9 together with the atom to which they are both bonded form a C 3 -C 7 cycloalkyl ring; and
R 10 , R 11 , R 12 , R 13 and R 14 are each independently selected from the group consisting of H, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonylamino, C 1 -C 6 alkyl, C 1 -C 6 alkylamino, C 1 -C 6 alkylcarboxamide, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonamide, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylureyl, amino, carbo-C 1 -C 6 alkoxy, carboxamide, carboxy, cyano, C 3 -C 6 cycloalkyl, C 3 -C 7 cycloalkylcarbonyl, C 2 -C 8 dialkylamino, C 2 -C 6 dialkylcarboxamide, C 1 -C 6 haloalkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 haloalkylsulfonyl, halogen, heteroaryl, heterocyclyl, hydroxyl, nitro, phenyl, sulfonamide and sulfonic acid; wherein said phenyl group is optionally substituted with 1, 2 or 3 halogens;
comprising the coupling of the following piperazine
with the following imidazopyridine carboxylic acid derivative
and wherein W is OH or Cl.
61 . The process of claim 60 , further comprising removing a Boc protecting group from the following Alkylated Boc-piperazine
to obtain a the following piperazine
62 . The process of claim 61 , further comprising reducing the ketone of the following amide
to obtain a the following Alkylated Boc-piperazine
63 . The process of claim 62 , further comprising the coupling of the following phenylacetic acid derivative
with the following Boc-piperazine
to obtain the following amideJoin the waitlist — get patent alerts
Track US2019142826A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.