US 2015/0307489 A1Published application

Pyrimidine pde10 inhibitors

AssigneeMerck Sharp & Dohme Corp.

InventorsScott D. Kuduk, Casey C. McComas, Thomas S. Reger

Life of this patent

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Abstract

The present invention is directed to pyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

Claims18

Dependent claims

A compound of the formula I:

wherein:
A is selected from the group consisting of:
(1) pyridyl,
(2) quinolinyl,
(3) cyclopentapyridinyl and
(4) tetrahydroquinolinyl,
said pyridyl, quinolinyl, and cyclopentapyridinyl optionally substituted with 1 to 3 groups of Ra
W is cycylopropyl or —CH(CH3)—CH2—
R4 is selected from the group consisting of:
(1) oxazolyl,
(2) oxadiazolyl,
(3) triazolyl,
(4) isoxazolone,
(5) pyrazolone,
(6) pyrazolopyridinyl,
(7) dioxaspirodecanyl,
(8) pyrazinyl,
(9) pyrrolyl,
(10) imidazopyridinyl,
(11) pyridyl,
(12) pyrimidinyl,
(13) indolyl,
(14) pyranone,
(15) pyranyl,
(16) pyridazinyl,
(17) furanone,
(18) isothiazolyl,
(19) dihydropyrazolone,
(20) pyrazolyl,
(21) thiazolyl,
(22) phenyl,
(23) cyclohexanone,
(24) cyclohexyl,
(25) cyclohexenone,
(26) cyclopentenone
(27) cyclopentanone,
(28) cyclopentanyl,
(29) pyridinone
(30) C2-6 alkenyl,
said group (1) through (29) optionally substituted with 1 to 3 groups of Ra′,
Ra selected from the group consisting of:
(1) (O)mC1-4, haloalkyl, said alkyl optionally substituted with 1 to 3 groups of Rb,
(2) halogen,
(3) OR,
(4) C1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from Rb,
(5) C3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from Rb,
(6) —O(CH2)ncycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from Rb,
(7) C5-10heterocyclyl, where the heterocyclyl is unsubstituted or substituted with one or more substituents selected from Rb,
(8) —(C═O)m—N(R)2,
(9) —CO2R,
(10) —CN,
(11) —O—,
(12) —O(CHR)CH2OR, and
(13) S(O)pR;
Rb is selected from the group consisting of:
(1) (CH2)nOR,
(2) CF3,
(3) CF2
(4) C1-6 alkyl,
(5) cyano,
(6) N(R)2,
(7) halogen;
R is selected from the group consisting of:
(1) hydrogen,
(2) C1-6 alkyl, said alkyl optionally substituted with 1 to 3 groups of Rb, and
(3) (O)mC1-4, haloalkyl,
m is 0 or 1,
n is 0, 1, 2, 3, or 4,
p is 1 or 2,
or a pharmaceutically acceptable salt thereof, with the proviso that
1) when A is methoxypyridyl and R4 is pyrazole then the pyrazole cannot be substituted with ethanol, methanol, propanol, methoxyethyl, methylbutyl, methylpropranol, pyridyl, CH2pyridyl, methylmethanol, or with only methyl groups;
2) when A is methylpyridyl or pyridyl and R4 is pyrazole then the pyrazole can't only be substituted with methyl;
3) when A is methoxypyridyl or methyl pyridyl and R4 is pyridyl, then the pyridyl must be substituted and when substituted with a methyl, methoxy, or propanol must contain at least one other substituent;
4) when R4 is pyridinone then A cannot be pridyl;
5) A is not methoxypyridyl when R4 is imidazopyridine;
6) when A is methoxypyridyl then R4 is not methyltriazole;
7) when A is cyclopentapyridine and R4 is pyrazole then the pyrazole cannot be substituted with three methyl groups;
8) when A is methylpyridyl or methoxypyridyl and R4 is a substituted cyclohexyl or cyclohexenol then the substituent can't only be a hydroxyl group.

75 more elements

A compound which is selected from the group consisting of:

2-Methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(3-(trifluoromethyl)phenyl)pyrimidine,
5-(2,4-dimethylphenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
5-(3-isopropoxyphenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
5-(3-isopropylphenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(2-(trifluoromethoxy)phenyl)pyrimidine,
5-(2,6-difluorophenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
5-(3,5-difluorophenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
5-(2-ethylphenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
5-(4-fluoro-3-methylphenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(4-(trifluoromethyl)phenyl)pyrimidine,
5-(2,6-dimethylphenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(3-(trifluoromethoxy)phenyl)pyrimidine,
5-(2,5-dimethylphenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(2-(trifluoromethyl)phenyl)pyrimidine,
5-(3,4-difluorophenyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
5-(2-methoxypyridin-3-yl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(3-(trifluoromethyl)pyridin-4-yl)pyrimidine,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5,5′-bipyrimidine,
5-(2-fluoropyridin-4-yl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
5-(6-chloropyridin-3-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(2-fluoropyridin-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
4-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)benzoic acid (enantiomer A) and (enantiomer B),
2-((1S,2S)-2-((2-methyl-5-p-tolylpyrimidin-4-yloxy)methyl)cyclopropyl)quinoline (enantiomer A) and (enantiomer B),
2-((1S,2S)-2-((2-methyl-5-(pyridin-4-yl)pyrimidin-4-yloxy)methyl)cyclopropyl)quinoline (enantiomer A) and (enantiomer B),
2-((1S,2S)-2-((5-(4-methoxyphenyl)-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)quinoline (enantiomer A) and (enantiomer B),
2-((1S,2S)-2-((5-(4-ethylphenyl)-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)quinoline (enantiomer A) and (enantiomer B),
4-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)benzonitrile (enantiomer A) and (enantiomer B),
1-(4-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)phenyl)ethanol (enantiomer A) and (enantiomer B),
2-((1S,2S)-2-((2-methyl-5-m-tolylpyrimidin-4-yloxy)methyl)cyclopropyl)quinoline (enantiomer A) and (enantiomer B),
(4-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)phenyl)methanol (enantiomer A) and (enantiomer B),
5-(3-ethoxyphenyl)-2-methyl-6-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-1-ium 2,2,2-trifluoroacetate (enantiomer A) and (enantiomer B),
2-((1S,2S)-2-((2-methyl-5-(6-methylpyridin-3-yl)pyrimidin-4-yloxy)methyl)cyclopropyl)-quinoline,
2-((1S,2S)-2-((2-methyl-5,5′-bipyrimidin-4-yloxy)methyl)cyclopropyl)quinoline (enantiomer A) and (enantiomer B),
2-(4-Methyl-5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy) pyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
2-(5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol (enantiomer A) and (enantiomer B),
methyl 5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)picolinate,
5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1H-indole,
3-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-2H-pyran-2-one,
5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-2H-pyran-2-one,
5-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)-methoxy)pyrimidine,
4-chloro-3-methoxy-5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridazine,
2-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-4-ol,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-vinylpyrimidine,
5-(4,6-dimethylpyridin-3-yl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)-methoxy)pyrimidine,
3-methoxy-5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridazine,
5-(6-(2-methoxyethoxyl)pyridin-3-yl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
3-methyl-5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridazine,
3-bromo-5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridazine,
4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)furan-2(5H)-one,
5-(6-isopropoxy-2-methylpyridin-3-yl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)isothiazole,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(6-(methylsulfonyl)pyridin-3-yl)pyrimidine,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(6-(methylsulfinyl)pyridin-3-yl)pyrimidine (R or S),
2-(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyrazin-2-yl)propan-2-ol,
2,2-difluoro-1-(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)ethanol (R or S),
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-ol,
4′-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2′-methyl-5,5′-bipyrimidin-2-ol,
2-(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yloxy)propane-1,3-diol,
5-(6-(cyclopropylmethoxy)pyridin-3-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)isothiazole,
5-(2-isopropoxypyridin-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(2-ethoxypyridin-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
3-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclopent-2-enone,
3-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclopent-2-enone (R,R),
3-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclopentanone,
(1R,3S)-3-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclopentanol,
(1R,3R)-3-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclopentanol,
5-(4-bromophenyl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrimidine,
2,2,2-trifluoro-1-(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)ethanol (R or S),
2,2,2-trifluoro-1-(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)ethanol (S or R),
5-(6-ethylpyridin-3-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(5-bromopyridin-2-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(2-chloro-5-(trifluoromethyl)pyridin-3-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(2-chloro-5-(trifluoromethyl)pyridin-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
1-(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)cyclopentanol,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1H-indole,
3-(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)oxetan-3-ol,
1-(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)cyclobutanol,
5-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)phenyl)-1,2,4-oxadiazole,
3-(chloromethyl)-5-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)phenyl)-1,2,4-oxadiazole,
(5-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)phenyl)-1,2,4-oxadiazol-3-yl)methanol,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyrazine-2-carboxylic acid,
methyl 5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyrazine-2-carboxylate,
(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyrazin-2-yl)methanol,
6-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridazine-3-carboxylic acid,
2-(6-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridazin-3-yl)propan-2-ol,
(6-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridazin-3-yl)methanol,
3-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-6-methylpyridazine,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-N-methylpicolinamide,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-N-(2,2,2-trifluoroethyl)picolinamide,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)picolinamide,
N-(2-hydroxyethyl)-5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)picolinamide,
N-(2-hydroxyethyl)-4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)benzamide,
2-amino-4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)nicotinonitrile,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile,
ethyl 6-hydroxy-4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)nicotinate,
5-(2-chloro-5-methoxypyridin-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(2-chloro-5-((2-(trimethylsilyl)ethoxy)methoxy)pyridin-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile,
2,2,2-trifluoro-1-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1H-pyrazol-3-yl)ethanol,
5-(3,6-dihydro-2H-pyran-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
(1-methyl-4-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1H-pyrazol-3-yl)methanol (1S,2S),
2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)-5-(6-(trifluoromethyl)pyridin-3-yl)pyrimidine,
2-(4-methyl-5-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
2-(6-methyl-5-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
1-(5-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)cyclopentanol,
1-(4-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)phenyl)ethanol,
2-(5-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
2-(5-(4-(((1R,2R)-2-(5-bromopyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
5-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidine,
2-(4-methyl-5-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
2-((1S,2S)-2-((5-(3-fluoropyridin-2-yl)-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)-quinoline,
2-((1S,2S)-2-((2-methyl-5-(4-methylpyridin-2-yl)pyrimidin-4-yloxy)methyl)cyclopropyl)-quinoline,
2-((1S,2S)-2-((2-methyl-5-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrimidin-4-yloxy)methyl)-cyclopropyl)quinoline,
3-methyl-6-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)imidazo[1,2-a]pyridine,
2-((1S,2S)-2-((5-(5-methoxyimidazo[1,2-a]pyridin-7-yl)-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)quinoline,
5-methoxy-7-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)imidazo[1,2-a]pyridine,
2-((1S,2S)-2-((5-(imidazo[1,2-a]pyridin-3-yl)-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)-quinoline,
2-((1S,2S)-2-((5-(imidazo[1,2-a]pyridin-8-yl)-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)-quinoline,
8-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)imidazo[1,2-a]pyridine,
2-((1S,2S)-2-((5-(imidazo[1,2-a]pyridin-6-yl)-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)-quinoline,
6-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)imidazo[1,2-a]pyridine,
2-(6-Methyl-5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
2-methyl-1-(5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-1-ol,
1-(5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)ethanol,
5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine,
1-(5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-1-ol,
2,2,2-trifluoro-1-(5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)ethanol,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(3-methylpyridin-4-yl)pyrimidine,
1-(5-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)ethanol,
5-(3-methoxypyridin-4-yl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)-methoxy)pyrimidine,
2-((1S,2S)-2-((2-methyl-5-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyrimidin-4-yloxy)methyl)-cyclopropyl)quinoline (enantiomer A) and (enantiomer B),
2-((1S,2S)-2-((2-methyl-5-(2-methylpyridin-4-yl)pyrimidin-4-yloxy)methyl)cyclopropyl)-quinoline,
(5-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)methanol,
2-((1S,2S)-2-((2-methyl-5-(pyridin-3-yl)pyrimidin-4-yloxy)methyl)cyclopropyl)quinoline,
2-((1S,2S)-2-((2-methyl-5-(6-(trifluoromethyl)pyridin-3-yl)pyrimidin-4-yloxy)methyl)-cyclopropyl)quinoline,
2-(5-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
1-(1-methyl-4-(2-methyl-4-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1H-pyrazol-3-yl)ethanol,
1-(1-methyl-4-(2-methyl-4-(((1S,2S)-2-(4-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1H-pyrazol-3-yl)ethanol,
1-(1-methyl-4-(2-methyl-4-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1H-pyrazol-3-yl)ethanol,
1-(4-(4-(((1S,2S)-2-(5-ethylpyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1H-pyrazol-3-yl)ethanol,
1-(4-(4-(((1R,2R)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1H-pyrazol-3-yl)ethanol (enantiomer A, R or S),
1-(4-(4-(((1R,2R)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1H-pyrazol-3-yl)ethanol (enantiomer A, S or R),
1-(4-(4-(((1R,2R)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1H-pyrazol-3-yl)ethanol (enantiomer B, R or S),
1-(4-(4-(((1R,2R)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1H-pyrazol-3-yl)ethanol (enantiomer B, S or R),
1-(1-methyl-4-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1H-pyrazol-3-yl)ethanol (R or S),
1-(1-methyl-4-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1H-pyrazol-3-yl)ethanol (S or R),
2,2-difluoro-1-(1-methyl-4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)-methoxy)pyrimidin-5-yl)-1H-pyrazol-3-yl)ethanol,
4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)benzonitrile,
4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)benzoic acid,
2-(5-(2-methyl-4-(((1S,2S)-2-(3-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol (enantiomer A) and (enantiomer B),
2-(5-(2-methyl-4-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol (enantiomer A),
2-(5-(2-methyl-4-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol (1R,2R, mixture),
2-(5-(2-methyl-4-(((1S,2S)-2-(4-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol (enantiomer A) and (enantiomer B),
2-(5-(4-(((1S,2S)-2-(5-fluoropyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
2-(5-(4-(((1S,2S)-2-(5-ethylpyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)pyridin-2-yl)propan-2-ol (enantiomer A) and (enantiomer B),
6-((1S,2S)-2-((5-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)nicotinonitrile,
2-(5-(2-methyl-4-(((1S,2S)-2-(5-(trifluoromethyl)pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)pyridin-2-yl)propan-2-ol,
2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(1,4-dioxaspiro-[4.5]decan-8-yl)pyrimidine,
4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexanone,
2-methyl-4-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrimidine,
4-(2-methyl-4-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexanone,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrimidine,
4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexanone,
2-((1S,2S)-2-((2-methyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrimidin-4-yloxy)methyl)-cyclopropyl)quinoline,
4-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexanone,
Trans-4-(2-methyl-4-(((1S,2R)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexanol,
(1R,4s)-4-(2-methyl-4-(((1S,2R)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexanol,
4-(((1S,2R)-2-(5-ethylpyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrimidine,
4-(4-(((1S,2R)-2-(5-ethylpyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexanone,
Trans-4-(4-(((1S,2R)-2-(5-ethylpyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexanol,
(1R,4s)-4-(4-(((1S,2R)-2-(5-ethylpyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexanol,
2-methyl-4-(((1S,2R)-2-(pyridin-2-yl)cyclopropyl)methoxy)-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrimidine,
Trans-4-(2-methyl-4-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexanol,
4-(((1S,2S)-2-(6-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrimidine,
2-methyl-4-(((1S,2S)-2-(4-methylpyridin-2-yl)cyclopropyl)methoxy)-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrimidine,
4-(4-(((1S,2S)-2-(6-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexanone,
4-(2-methyl-4-(((1S,2S)-2-(4-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexanone,
2-((2S)-2-methyl-3-(2-methyl-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrimidin-4-yloxy)propyl)quinoline,
(7R,8S)-8-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1,4-dioxaspiro[4.5]decan-7-ol,
8-(2-methyl-4-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)-1,4-dioxaspiro[4.5]decan-8-ol,
3-(4-(((1S,2S)-2-(5-Methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexanone,
5-Cyclohexyl-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl) methoxy) pyrimidine,
5-(4,4-Difluorocyclohexyl)-2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)-methoxy)pyrimidine,
(trans)-4-Fluoro-4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexanol,
5-(1-fluorocyclohexyl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
(cis)1-Methyl-4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy) pyrimidin-5-yl)cyclohexanol,
(trans)1-Methyl-4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy) pyrimidin-5-yl)cyclohexanol,
(cis)1-Ethyl-4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy) pyrimidin-5-yl)cyclohexanol,
(trans)1-Ethyl-4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-1)cyclopropyl)methoxy) pyrimidin-5-yl)cyclohexanol,
cis-Ethyl4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexanecarboxylate,
cis-4-(4-(((1S,2S)-2-(5-Methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexanecarboxylic acid,
cis-4-(4-(((1S,2S)-2-(5-Methoxypyridin-2-yl)cyclopropyl)methoxy)-2-m-ethylpyrimidin-5-yl)cyclohexanecarboxamide,
trans-4-(4-(((1S,2S)-2-(5-Methoxypyridin-2-yl)cyclopropyl)methoxy)-2-m-ethylpyrimidin-5-yl)cyclohexanecarboxamide,
(trans) 2-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)cyclohexyl)propan-2-ol,
(cis)2-(4-(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)cyclohexyl)propan-2-ol,
5-(4-(1H-tetrazol-5-yl)phenyl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)pyrimidine,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(4-(1-methyl-1H-tetrazol-5-yl)phenyl)pyrimidine,
5-(4-(2-ethyl-2H-tetrazol-5-yl)phenyl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(4-(1-ethyl-1H-tetrazol-5-yl)phenyl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(4-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenyl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(4-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenyl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(6-(2H-tetrazol-5-yl)pyridin-3-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)-methoxy)-2-methylpyrimidine,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)pyrimidine,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(6-(1-methyl-1H-tetrazol-5-yl)pyridin-3-yl)pyrimidine,
5-(6-(2-ethyl-2H-tetrazol-5-yl)pyridin-3-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(6-(1-ethyl-1H-tetrazol-5-yl)pyridin-3-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(2H-tetrazol-5-yl)pyrimidine,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(2-methyl-2H-tetrazol-5-yl)pyrimidine,
5-(2-ethyl-2H-tetrazol-5-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(2-(difluoromethyl)-2H-tetrazol-5-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1,2-dihydropyrazol-3-one,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1,2-dimethyl-1,2-dihydropyrazol-3-one,
5-(3-methoxy-1-methyl-1H-pyrazol-5-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1,2-dihydropyrazol-3-one,
4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)isoxazol-5(2H)-one,
4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-2-methylisoxazol-5(2H)-one,
4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1-methyl-1,2-dihydropyrazol-3-one,
4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-5-(1H-1,2,3-triazol-4-yl)pyrimidine,
5-(3-(difluoromethyl)-3H-1,2,3-triazol-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
5-(1-ethyl-1H-1,2,3-triazol-4-yl)-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidine,
ethyl 5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-3H-1,2,3-triazole-4-carboxylate,
(5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-3H-1,2,3-triazol-4-yl)methanol,
3-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)phenyl)-1,2,4-oxadiazole,
3-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)phenyl)-5-methyl-1,2,4-oxadiazole,
(3-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)phenyl)-1,2,4-oxadiazol-5-yl)methanol,
5-(4-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)phenyl)-3-methyl-1,2,4-oxadiazole,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1,2,4-oxadiazole,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)oxazole,
(3-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-1,2,4-oxadiazol-5-yl)methanol,
5-(4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-5-yl)-4-methyloxazole,
or a pharmaceutically acceptable salt thereof.

231 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/443,619Filed 15 Nov 2013
Priority: 20 Nov 2012
Published: 29 Oct 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 25/18
Drugs for disorders of the nervous system: antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…

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Application61/728,464Us provisional application · filed 20 Nov 2012
US 9,663,513 B2Related patent
US 2015/0307489 A1This patent

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Abstract

A compound of the formula I:

wherein:
A is selected from the group consisting of:
(1) pyridyl,
(2) quinolinyl,
(3) cyclopentapyridinyl and
(4) tetrahydroquinolinyl,
said pyridyl, quinolinyl, and cyclopentapyridinyl optionally substituted with 1 to 3 groups of Ra
W is cycylopropyl or —CH(CH3)—CH2—
R4 is selected from the group consisting of:
(1) oxazolyl,
(2) oxadiazolyl,
(3) triazolyl,
(4) isoxazolone,
(5) pyrazolone,
(6) pyrazolopyridinyl,
(7) dioxaspirodecanyl,
(8) pyrazinyl,
(9) pyrrolyl,
(10) imidazopyridinyl,
(11) pyridyl,
(12) pyrimidinyl,
(13) indolyl,
(14) pyranone,
(15) pyranyl,
(16) pyridazinyl,
(17) furanone,
(18) isothiazolyl,
(19) dihydropyrazolone,
(20) pyrazolyl,
(21) thiazolyl,
(22) phenyl,
(23) cyclohexanone,
(24) cyclohexyl,
(25) cyclohexenone,
(26) cyclopentenone
(27) cyclopentanone,
(28) cyclopentanyl,
(29) pyridinone
(30) C2-6 alkenyl,
said group (1) through (29) optionally substituted with 1 to 3 groups of Ra′,
Ra selected from the group consisting of:
(1) (O)mC1-4, haloalkyl, said alkyl optionally substituted with 1 to 3 groups of Rb,
(2) halogen,
(3) OR,
(4) C1-6 alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from Rb,
(5) C3-6 cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from Rb,
(6) —O(CH2)ncycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from Rb,
(7) C5-10heterocyclyl, where the heterocyclyl is unsubstituted or substituted with one or more substituents selected from Rb,
(8) —(C═O)m—N(R)2,
(9) —CO2R,
(10) —CN,
(11) —O—,
(12) —O(CHR)CH2OR, and
(13) S(O)pR;
Rb is selected from the group consisting of:
(1) (CH2)nOR,
(2) CF3,
(3) CF2
(4) C1-6 alkyl,
(5) cyano,
(6) N(R)2,
(7) halogen;
R is selected from the group consisting of:
(1) hydrogen,
(2) C1-6 alkyl, said alkyl optionally substituted with 1 to 3 groups of Rb, and
(3) (O)mC1-4, haloalkyl,
m is 0 or 1,
n is 0, 1, 2, 3, or 4,
p is 1 or 2,
or a pharmaceutically acceptable salt thereof, with the proviso that
1) when A is methoxypyridyl and R4 is pyrazole then the pyrazole cannot be substituted with ethanol, methanol, propanol, methoxyethyl, methylbutyl, methylpropranol, pyridyl, CH2pyridyl, methylmethanol, or with only methyl groups;
2) when A is methylpyridyl or pyridyl and R4 is pyrazole then the pyrazole can't only be substituted with methyl;
3) when A is methoxypyridyl or methyl pyridyl and R4 is pyridyl, then the pyridyl must be substituted and when substituted with a methyl, methoxy, or propanol must contain at least one other substituent;
4) when R4 is pyridinone then A cannot be pridyl;
5) A is not methoxypyridyl when R4 is imidazopyridine;
6) when A is methoxypyridyl then R4 is not methyltriazole;
7) when A is cyclopentapyridine and R4 is pyrazole then the pyrazole cannot be substituted with three methyl groups;
8) when A is methylpyridyl or methoxypyridyl and R4 is a substituted cyclohexyl or cyclohexenol then the substituent can't only be a hydroxyl group.

75 more elements

Facts

Application

14/443,619Filed 15 Nov 2013

Priority

20 Nov 2012

Published

29 Oct 2015

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 25/18
Drugs for disorders of the nervous system: antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…