US2017173016A1PendingUtilityA1
Heterocyclic compounds and their use for the treatment of neurodegenerative tauopathies
Est. expirySep 19, 2032(~6.2 yrs left)· nominal 20-yr term from priority
Inventors:Carlo BallatoreKurt R. BrundenAdam T. HoyeVirginia M.Y. LeeAmos B. Smith, IiiJohn Q. Trojanowski
A61K 31/519A61K 31/506A61P 25/00A61P 25/16A61K 31/4985A61K 31/53A61K 31/4196A61K 31/50A61K 31/5377A61K 31/501
53
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Claims
Abstract
The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds and their use in the treatment of neurodegenerative disorders.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
1 . A method of treating a neurodegenerative disease in a patient comprising administering to the patient a therapeutically effective amount of a compound of formula I:
wherein
R 1 is H, Cl, F, or Br;
R 2 is C 1-6 alkyl or substituted C 1-6 alkyl;
R 3 is H; or R 2 and R 3 , together with the N atom to which they are attached, form a heterocycloC 3-6 alkyl;
R 4 is H, Cl, F, or Br;
R 5 is H, Cl, F, or Br;
R 6 is F, Cl, Br, —N 3 , —OC 1-6 alkyl; —OC 1-6 alkyleneNR 7 R 8 , wherein R 7 and R 8 are each independently H or C 1-6 alkyl; and
R 9 is pyridinyl, pyrimidyl, pyrazinyl, imidazolyl, pyrrolyl, pyrazolyl, quinolinyl, isoquinolinyl, thienyl, or furyl, each of which may be optionally substituted with one or more of F, Cl, Br, or C 1-6 alkyl;
or a stereochemical isomer thereof;
or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein R 1 is Cl.
3 . The method of claim 1 , wherein R 2 is C 1-6 alkyl.
4 . The method of claim 3 , wherein R 2 is methyl, ethyl, propyl, or isopropyl.
5 . The method of claim 1 , wherein R 2 is substituted C 1-6 alkyl.
6 . The method of claim 5 , wherein R 2 is —CH(CH 3 )CF 3
7 . The method of claim 5 , wherein R 2 is —CH 2 CF 3 .
8 . The method of claim 1 , wherein R 3 is H.
9 . The method of claim 1 , wherein R 4 is F.
10 . The method of claim 1 , wherein R 5 is F.
11 . The method of claim 1 , wherein R 4 and R 5 are each F.
12 . The method of claim 1 , wherein R 6 is F.
13 . The method of claim 1 , wherein R 6 is —OtBu.
14 . The method of claim 1 , wherein R 6 is —OC 1-6 alkyleneNR 7 R 8 and R 7 and R 8 are each C 1-6 alkyl.
15 . The method of claim 14 , wherein R 6 is —O—CH 2 CH 2 CH 2 —N(CH 3 ) 2 .
16 . The method of claim 1 , wherein R 6 is —OC 1-6 alkyleneNR 7 R 8 ; R 7 is H; and R 8 is C 1-6 alkyl.
17 . The method of claim 16 , wherein R 6 is —O—CH 2 CH 2 CH 2 —NH(CH 3 ).
18 . The method of claim 1 , wherein R 9 is 2-pyridinyl, 2-pyrimidyl, 2-pyrazinyl, or 1-pyrazolyl.
19 . The method of claim 1 , wherein the compound of formula I is
X
R 1
R 2
R 3
R 4
R 5
R 6
N
Cl
—CH(CH 3 )CF 3 (S)
H
F
F
F
N
Cl
—CH(CH 3 )CF 3 (R)
H
F
F
F
N
Cl
—CH(CH 3 )CF 3 (S,R)
H
F
F
F
N
Cl
H
H
F
F
F
CH
Cl
—CH(CH 3 )CF 3 (S)
H
F
F
F
CH
Cl
—CH(CH 3 )CF 3 (R)
H
F
F
F
CH
Cl
—CH(CH 3 )CF 3 (S,R)
H
F
F
F
CH
Cl
H
H
F
F
F
N
Cl
—CH(CH 3 )CF 3 (S)
H
F
F
—OCH 2 CH 2 CH 2 N(CH 3 ) 2
N
Cl
—CH(CH 3 )CF 3 (R)
H
F
F
—OCH 2 CH 2 CH 2 N(CH 3 ) 2
N
Cl
—CH(CH 3 )CF 3 (S,R)
H
F
F
—OCH 2 CH 2 CH 2 N(CH 3 ) 2
CH
Cl
H
H
F
F
—OCH 2 CH 2 CH 2 N(CH 3 ) 2
CH
Cl
H
H
F
F
—OtBu
CH
Cl
—CH(CH 3 )CF 3 (S)
H
F
F
—OCH 2 CH 2 CH 2 N(CH 3 ) 2
CH
Cl
—CH(CH 3 )CF 3 (S)
H
F
F
—OCH 2 CH 2 CH 2 NH(CH 3 )
20 . The method of claim 1 , wherein the compound of formula I is
21 . The method of claim 1 , wherein the neurodegenerative disease is characterized by a tauopathy or compromised microtubule function in the brain of the patient.
22 . The method of claim 1 , wherein the neurodegenerative disease is Alzheimer's disease, frontotemporal lobar degeneration, Pick's disease, progressive supranuclear palsy (PSP), corticobasal degeneration, Parkinson's disease (PD), PD with dementia, Lewy body disease with dementia, or amyotrophic lateral sclerosis.
23 . The method of claim 1 , wherein the neurodegenerative disease is traumatic brain injury, in particular, repetitive traumatic brain injury and chronic traumatic encephalopathy, or post traumatic stress disorder.
24 . The method of claim 1 , wherein the neurodegenerative disease is schizophrenia.Cited by (0)
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