US 8,263,595 B2Granted

Triazolopyridine compounds and their use as ask inhibitors

AssigneeMerck Serono SA

InventorsDominique Swinnen, Catherine Jorand-Lebrun, Tania Grippi-Vallotton, Mathilde Muzerelle, Amanda Royle, Jacqueline MacRitchie, Richard Hill, Jeffrey P. Shaw

Life of this patent

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Abstract

The present invention relates to triazolopyridine compounds according to Formula (I), their use as medicament, for treating autoimmune disorders, inflammatory diseases, cardiovascular diseases and/or neurodegenerative diseases and a process for their preparation.

Claims5

Dependent claims

A triazolopyridine compound of formula I-1:

wherein:
R2 is selected from:
a) hydrogen;
or
b) halogen;
R3 is selected from:
a) hydrogen;
b) halogen;
or
c) C1-C6-alkyl that is unsubstituted or is substituted with at least one fluoro;
R5 is selected from:
a) C1-C6-alkyl that is unsubstituted or is substituted with at least one of the following groups:
i) alkoxycarbonyl,
ii) C1-C6-alkoxy,
iii) —NC(O)R′ wherein R′ is an aryl that is unsubstituted or is substituted with C1-C6-alkyl, or
iv) benzyloxy;
b) aryl-C1-C6-alkyl;
c) 5 or 6-membered heteroaryl-C1-C6-alkyl having a heteroatom selected from N, S or O that is unsubstituted or is substituted with C1-C6-alkyl, halogen or C1-C6-alkoxy;
d) C3-C6-cycloalkyl that is unsubstituted or is substituted with phenyl;
e) 3 to 8-membered heterocycloalkyl having a heteroatom selected from N, S or O that is substituted with an acyl group;
f) aryl that is unsubstituted or is substituted with at least one of the following groups:
i) C1-C6-alkyl,
ii) halogen,
iii) C1-C6-alkoxy,
iv) perfluoro-C1-C6-alkyl,
v) at least one C1-C6-alkoxy that is unsubstituted or is substituted with C1-C6-alkoxy carbonyl,
vi) phenyl,
vii) C1-C6-alkyl sulfonyl,
viii) —NHC(O)C1-C6-alkyl,
ix) amino-C1-C6-alkyl wherein amino is selected from —NH2, —NHC1-C6-alkyl, —N(C1-C6-alkyl)2, N(C1-C6-alkyl)(C1-C6-alkoxy-C1-C6-alkyl), and the two substituents C1-C6-alkyl can be the same or different, and wherein the two substituents may form a 3 to 8-membered heterocycloalkyl with the N to which they are attached and wherein the heterocycloalkyl is unsubstituted or is substituted with C1-C6-alkyl or with hydroxy,
x) —N(C1-C6-alkyl) (C1-C6-alkoxy-C1-C6-alkyl),
xi) 5 to 6-membered heterocycloalkyl-C1-C6-alkyl having a heteroatom selected from N and O, or
xii) amido-C1-C6-alkyl;
g) 5 to 10-membered heteroaryl having at least one heteroatom selected from N, O or S optionally substituted with halogen;
or
h) pyridinyl that is unsubstituted or is substituted with at least one of the following groups:
i) halogen,
ii) C1-C6-alkyl,
iii) amino-C1-C6-alkyl wherein amino is selected from —NH2, —NHC1-C6-alkyl or —N(C1-C6-alkyl)2, wherein the two substituents C1-C6-alkyl can be the same or different, and wherein the two substituents may form a 3 to 8-membered heterocycloalkyl with the N to which they are attached and wherein the heterocycloalkyl is unsubstituted or is substituted with C1-C6-alkyl or hydroxy,
iv) —NH(hydroxy-C1-C6-alkyl),
v) —NH-(5-membered heteroaryl-C1-C6-alkyl having as heteroatom O),
vi) 5 or 6-membered heterocycloalkyl-C1-C6-alkyl having at least one heteroatom selected from O or N,
vii) 5 or 6-membered heterocycloalkyl having at least one heteroatom selected from O or N and that is unsubstituted or is substituted with hydroxy, —C(O)OR′ wherein R′ is C1-C6-alkyl, halogen or C1-C6-alkyl,
viii) amino,
ix) —NH(amino-C1-C6-alkyl), or
x) —N(C1-C6-alkyl)2;
R6 is selected from:
a) C1-C6-alkyl that is unsubstituted or is substituted with one or two hydroxy groups;
b) phenyl substituted with at least one of the following groups:
i) halogen,
ii) C1-C6-alkyl, or
iii) C1-C6-alkoxy;
c) 5 or 6-membered heterocycloalkyl having a heteroatom selected from O or N and substituted with C1-C6-alkyl;
d) C3-C8-cycloalkyl substituted with R8;
or
e) —(CH2)nR9 wherein n equals 1, 2 or 3;
R7 is:
a) hydrogen;
or
b) C1-C6-alkyl;
R8 is selected from:
a) hydrogen;
b) hydroxy;
c) C1-C6-alkyl that is unsubstituted or is substituted with hydroxy;
d) C(O)O—C1-C6-alkyl;
or
e) —NH2;
and
R9 is selected from:
a) C3-C8-cycloalkyl that is unsubstituted or is substituted with an unsubstituted C1-C6-alkyl;
b) 5 or 6-membered heterocycloalkyl having a heteroatom selected from N and O and that is unsubstituted or is substituted with C1-C6-alkyl;
c) 5 or 6-membered heteroaryl having a heteroatom selected from N and O that is unsubstituted or is and that is unsubstituted or is substituted with C1-C6-alkyl;
or
d) phenyl.

71 more elements

A triazolopyridine compound selected from:

N-[5-(cyclopropylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-(5-pyrrolidin-1-yl[1,2,4]triazolo[1,5-a]pyridin-2-yl)nicotinamide;
N-[5-(cyclopentylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]benzamide;
N-{5-[(3-methoxypropyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}benzamide;
N-{5-[(2-furylmethyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}benzamide;
N-{5-[(tetrahydrofuran-2-ylmethyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}benzamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]benzamide;
N-(5-{[1-(hydroxymethyl)propyl]amino}[1,2,4]triazolo[1,5-a]pyridin-2-yl)benzamide;
N-{5-[(2-methoxyethyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}benzamide;
N-{5-[(2,3-dihydroxypropyl)amino][1,2,4]-triazolo[1,5-a]pyridin-2-yl}benzamide;
N-[5-(benzylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(cycloheptylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide dihydrochloride;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-y]nicotinamide;
N-(5-{[(5-methyl-2-furyl)methyl]amino}[1,2,4]triazolo[1,5-a]pyridin-2-yl)nicotinamide;
N-{5-[(tetrahydrofuran-2-ylmethyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}nicotinamide;
N-[5-(cyclooctylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-[cyclohexyl(methyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(tetrahydro-2H-pyran-4-ylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-{5-(1-methylpiperidin-4-yl)amino][1,2,4]-triazolo[1,5-a]pyridin-2-yl}nicotinamide;
N-{5-[(3-aminocyclohexyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}benzamide;
N-{5-[(1-methylpiperidin-4-yl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}benzamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(cyclohexylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(cycloheptylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(cyclopentylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-{5-[(cyclohexylmethyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl}nicotinamide;
N-{5-[(3-hydroxycyclohexyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}nicotinamide;
N-[5-[(4-tert-butylcyclohexyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(tetrahydro-2H-pyran-3-ylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]benzamide;
N-[5-(cycloheptylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-(morpholin-4-ylmethyl)benzamide;
N-{5-[(trans-4-hydroxycyclohexyl)amino][1,2,4]triazolo[1,5-a}pyridin-2-yl]nicotinamide;
N-[5-(cyclobutylamino)-7-(trifluoromethyl)[1,2,4]-triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-morpholin-4-ylnicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-[(dimethylamino)methyl]benzamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-3-(morpholin-4-ylmethyl)benzamide;
N-[5-[(cyclopropylmethyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
methyltrans-4-{[2-[(pyridin-3-ylcarbonyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-5-yl]amino}cyclohexanecarboxylate;
N-[5-{[(1RS,2RS)-2-(hydroxymethyl)cyclohexyl]amino}-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[6-bromo-5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(cycloheptylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]tetrahydro-2H-pyran-4-carboxamide;
N-(3-{[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino}-3-oxopropyl)benzamide;
N-[5-(isopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(sec-butylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(methylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-(2-pyrrolidin-1-ylethyl)nicotinamide;
N-5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-(morpholin-4-ylmethyl)nicotinamide;
N-{5-[(cyclohexylmethyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}nicotinamide;
N-{5-[(4-hydroxycyclohexyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}-3-methoxybenzamide;
N-[5-(cyclopentylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-2-furamide;
N-[7-chloro-5-(cyclobutylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[7-chloro-5-(cyclopentylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[7-chloro-5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(sec-butylamino)-7-chloro[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[7-chloro-5-(cyclopropylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-[(2-methoxyethyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-[(3-hydroxypropyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-[(2-hydroxyethyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(dimethylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N -[(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-2-pyridin-3-ylacetamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-(piperidin-1-ylmethyl)benzamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-(pyrrolidin-1-ylmethyl)benzamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-{[(2-methoxyethyl)(methyl)amino]methyl}benzamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-methylnicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-[(3-hydroxypropyl)amino]nicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-[(2-furylmethyl)amino]nicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide 1-oxide;
N-[5-(isopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-2-pyridin-3-ylacetamide trihydrochloride;
N-[5-[(1-ethylpropyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(isopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide 1-oxide;
N-[5-[(3-hydroxycyclohexyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide formic acid;
N-{7-chloro-5-[(3-hydroxycyclohexyl)amino][1,2,4]triazolo[1,5-a]pyridin-2-yl}nicotinamide formic acid;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]-triazolo[1,5-a]pyridin-2-yl]-4-[(dimethylamino)methyl]benzamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-[(2-oxopyrrolidin-1-yl)methyl]benzamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-pyrrolidin-1-ylnicotinamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-methylnicotinamide;
N-[5-{1R,2S)-2-(hydroxymethyl)cyclohexyl]amino}-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide hydrochloride;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-[(4-hydroxypiperidin-1-yl)methyl]benzamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-(pyrrolidin-1-ylmethyl)benzamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-(4-hydroxypiperidin-1-yl)nicotinamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]-triazolo[1,5-a]pyridin-2-yl]-6-piperazin-1-ylnicotinamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]-triazolo[1,5-a]pyridin-2-yl]-6-(dimethylamino)nicotinamide;
N-[6-bromo-5-(cyclopentylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-morpholin-4-ylnicotinamide;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-morpholin-4-ylnicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-(dimethylamino)nicotinamide;
tert-butyl 4-[5-({[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]-triazolo[1,5-a]pyridin-2-yl]amino}carbonyl)pyridin-2-yl]piperazine-1-carboxylate;
N-[5-(cyclohexylamino)[1,2,4]-triazolo[1,5-a]pyridin-2-yl]-4-[(4-hydroxypiperidin-1-yl)methyl]benzamide;
N-[5-(cyclohexylamino)[1,2,4]-triazolo[1,5-a]pyridin-2-yl]-6-(4-fluoropiperidin-1-yl)nicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-(1H-pyrazol-1-yl)nicotinamide;
tert-butyl 4-[5-({[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino}carbonyl)pyridin-2-yl]piperazine-1-carboxylate;
N-[5-(cyclopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-[(3-hydroxypropyl)amino]nicotinamide;
N-[5-(isopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-(morpholin-4-ylmethyl)nicotinamide;
N-[5-[(pyrrolidin-3-ylmethyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-(piperazin-1-ylmethyl)benzamide;
N-[5-(cyclohexylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-[(4-formylpiperazin-1-yl)methyl]benzamide;
N-[5-(piperidin-3-ylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(sec-butylamino)-7-chloro[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-[(2-methoxyethyl)(methyl)amino]nicotinamide;
N-[5-(sec-butylamino)-7-chloro[1,2,4]-triazolo[1,5-a]pyridin-2-yl]-6-[(3-hydroxypropyl)amino]nicotinamide;
N-[5-(sec-butylamino)-7-chloro[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-morpholin-4-ylnicotinamide;
N-[5-(sec-butylamino)-7-chloro[1,2,4]triazolo[1,5-a]pyridin-2-yl]-4-[(2-methoxyethyl)(methyl)amino]methyl]benzamide;
N-[5-(sec-butylamino)-7-chloro[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-methylnicotinamide;
N-[7-chloro-5-(isopropylamino)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-[(3-isopropoxyphenyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-[(3-fluoro-4-methoxyphenyl)amino]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-{[3-(benzyloxy)phenyl]amino}-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(sec-butylamino)-7-chloro[1,2,4-triazolo[1,5-a]pyridin-2-yl]-4-(morpholin-4-ylmethyl)benzamide;
N-[5-(isopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]-6-methylnicotinamide;
6-chloro-N-[5-(isopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
6-[(2-aminoethyl)amino]-N-[5-(isopropylamino)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
N-[5-(sec-butylamino)-7-methyl[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide;
or
N-[5-(isopropylamino)-7-methyl[1,2,4]triazolo[1,5-a]pyridin-2-yl]nicotinamide.

108 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/666,445Filed 20 Aug 2008 · us provisional application
Priority: EP 0711540831 Aug 2007
Published: US 2010/0197681 A15 Aug 2010
Granted: 11 Sep 2012
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 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…

Family

Application60/966,989Us provisional application · filed 31 Aug 2007
US 2010/0197681 A1Pre-grant publication · published 5 Aug 2010
US 8,263,595 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A triazolopyridine compound of formula I-1:

wherein:
R2 is selected from:
a) hydrogen;
or
b) halogen;
R3 is selected from:
a) hydrogen;
b) halogen;
or
c) C1-C6-alkyl that is unsubstituted or is substituted with at least one fluoro;
R5 is selected from:
a) C1-C6-alkyl that is unsubstituted or is substituted with at least one of the following groups:
i) alkoxycarbonyl,
ii) C1-C6-alkoxy,
iii) —NC(O)R′ wherein R′ is an aryl that is unsubstituted or is substituted with C1-C6-alkyl, or
iv) benzyloxy;
b) aryl-C1-C6-alkyl;
c) 5 or 6-membered heteroaryl-C1-C6-alkyl having a heteroatom selected from N, S or O that is unsubstituted or is substituted with C1-C6-alkyl, halogen or C1-C6-alkoxy;
d) C3-C6-cycloalkyl that is unsubstituted or is substituted with phenyl;
e) 3 to 8-membered heterocycloalkyl having a heteroatom selected from N, S or O that is substituted with an acyl group;
f) aryl that is unsubstituted or is substituted with at least one of the following groups:
i) C1-C6-alkyl,
ii) halogen,
iii) C1-C6-alkoxy,
iv) perfluoro-C1-C6-alkyl,
v) at least one C1-C6-alkoxy that is unsubstituted or is substituted with C1-C6-alkoxy carbonyl,
vi) phenyl,
vii) C1-C6-alkyl sulfonyl,
viii) —NHC(O)C1-C6-alkyl,
ix) amino-C1-C6-alkyl wherein amino is selected from —NH2, —NHC1-C6-alkyl, —N(C1-C6-alkyl)2, N(C1-C6-alkyl)(C1-C6-alkoxy-C1-C6-alkyl), and the two substituents C1-C6-alkyl can be the same or different, and wherein the two substituents may form a 3 to 8-membered heterocycloalkyl with the N to which they are attached and wherein the heterocycloalkyl is unsubstituted or is substituted with C1-C6-alkyl or with hydroxy,
x) —N(C1-C6-alkyl) (C1-C6-alkoxy-C1-C6-alkyl),
xi) 5 to 6-membered heterocycloalkyl-C1-C6-alkyl having a heteroatom selected from N and O, or
xii) amido-C1-C6-alkyl;
g) 5 to 10-membered heteroaryl having at least one heteroatom selected from N, O or S optionally substituted with halogen;
or
h) pyridinyl that is unsubstituted or is substituted with at least one of the following groups:
i) halogen,
ii) C1-C6-alkyl,
iii) amino-C1-C6-alkyl wherein amino is selected from —NH2, —NHC1-C6-alkyl or —N(C1-C6-alkyl)2, wherein the two substituents C1-C6-alkyl can be the same or different, and wherein the two substituents may form a 3 to 8-membered heterocycloalkyl with the N to which they are attached and wherein the heterocycloalkyl is unsubstituted or is substituted with C1-C6-alkyl or hydroxy,
iv) —NH(hydroxy-C1-C6-alkyl),
v) —NH-(5-membered heteroaryl-C1-C6-alkyl having as heteroatom O),
vi) 5 or 6-membered heterocycloalkyl-C1-C6-alkyl having at least one heteroatom selected from O or N,
vii) 5 or 6-membered heterocycloalkyl having at least one heteroatom selected from O or N and that is unsubstituted or is substituted with hydroxy, —C(O)OR′ wherein R′ is C1-C6-alkyl, halogen or C1-C6-alkyl,
viii) amino,
ix) —NH(amino-C1-C6-alkyl), or
x) —N(C1-C6-alkyl)2;
R6 is selected from:
a) C1-C6-alkyl that is unsubstituted or is substituted with one or two hydroxy groups;
b) phenyl substituted with at least one of the following groups:
i) halogen,
ii) C1-C6-alkyl, or
iii) C1-C6-alkoxy;
c) 5 or 6-membered heterocycloalkyl having a heteroatom selected from O or N and substituted with C1-C6-alkyl;
d) C3-C8-cycloalkyl substituted with R8;
or
e) —(CH2)nR9 wherein n equals 1, 2 or 3;
R7 is:
a) hydrogen;
or
b) C1-C6-alkyl;
R8 is selected from:
a) hydrogen;
b) hydroxy;
c) C1-C6-alkyl that is unsubstituted or is substituted with hydroxy;
d) C(O)O—C1-C6-alkyl;
or
e) —NH2;
and
R9 is selected from:
a) C3-C8-cycloalkyl that is unsubstituted or is substituted with an unsubstituted C1-C6-alkyl;
b) 5 or 6-membered heterocycloalkyl having a heteroatom selected from N and O and that is unsubstituted or is substituted with C1-C6-alkyl;
c) 5 or 6-membered heteroaryl having a heteroatom selected from N and O that is unsubstituted or is and that is unsubstituted or is substituted with C1-C6-alkyl;
or
d) phenyl.

71 more elements

Facts

Application

12/666,445Filed 20 Aug 2008 · us provisional application

Priority

EP 0711540831 Aug 2007

Published

US 2010/0197681 A15 Aug 2010

Granted

11 Sep 2012

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 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…