US 8,894,970 B2Granted

Arginase inhibitors and methods of use thereof

AssigneeCorridor Pharmaceuticals, Inc.

InventorsBruce Edward Tomczuk, Gary Lee Olson, Richard Scott Pottorf, Lijuan Jane Wang, Bhaskara Rao Nallaganchu, Yanqun Zhang

Life of this patent

Estimating the term…

Abstract

The present invention includes arginase enzyme inhibitors, compositions comprising these arginase inhibitors, and methods of treating or diagnosing conditions characterized either by abnormally high arginase activity or abnormally low nitric oxide levels in a mammal, comprising administering compositions of the invention to the mammal.

Claims2

Dependent claims

A compound selected from the group consisting of:

2-amino-6-borono-2-(2-(piperazin-1-yl)ethyl)hexanoic acid;
2-amino-2-(3-(4-benzylpiperazin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(4-(2-chlorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-cyanobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2,4-difluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2,3-difluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-dichlorobenzyl)piperazin-1-yl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3-(trifluoromethyl)benzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-(methylsulfonyl)benzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-fluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-difluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,5-difluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-phenethylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(2-(4-(3,4-dichlorobenzyl)piperazin-1-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-dichlorophenyl)piperazin-1yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(4-fluorophenyl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(2-(piperidin-2-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(2-(1-(3,4-dichlorobenzyl)piperidin-2-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(2-(1-(3,5-difluorobenzyl)piperidin-2-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(2-(1-(3,4-difluorobenzyl)piperidin-2-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(2-(1-(3,4-dichlorobenzyl)piperidin-3-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(3-(1-(3,4-dichlorobenzyl)piperidin-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(1-(3,4-difluorobenzyl)piperidin-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(1-(3,5-difluorobenzyl)piperidin-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-phenylpiperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-(5-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-difluorobenzyl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(pyrimidin-2-ylmethyl)piperidin-1-yl)propyl)hexanoic acid;
2-(3-(3H-spiro[isobenzofuran-1,4′piperidine]-1′-yl)propyl)-2-amino-6-boronohexanoic acid;
2-amino-6-borono-2(3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-chlorophenyl)-1H-pyrazol-1-yl)piperidin-1-yl) propylhexanoic acid;
2-amino-6-borono-2-(3-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-isopropylphenoxy)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-fluorophenyl)piperidin-1-yl)propylhexanoic acid;
2-amino-6-borono-2-(3-(4-(4-methoxyphenyl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)propyl) hexanoic acid;
2-amino-2-(3-(4-benzyl-4-hydroxypiperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-hydroxypiperidin-1-yl)propyl)hexanoic acid;
2-amino-2-(3-(4-((S)-2-amino-3-methylbutanoyloxy)piperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-2-(3-(4-benzamidopiperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-methyl-2-phenylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-2-(3-(2-benzylpiperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(2-(4-methoxyphenyl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(3-methoxylphenyl)pyrrolidin-1l-yl)propyl)hexanoic acid 2-amino-6-borono-2-(3-(2-(2-fluorobenzyl)pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(2-(trifluoromethyl)phenyl)pyrrolidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(2-(4-fluorophenyl)pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(3-chlorophenyl)pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-2-(3-(2-(biphenyl-4-yl)pyrrolidin-1-yl)propyl)-6-borono-hexanoic acid;
2-amino-6-borono-2-(3-(2-(3,4-dichlorophenyl)pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-2-(3-(azetidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(3-phenylazetidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-p-tolylazetidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-(3-(3,4-dichlorophenyl)ureido)azetidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(3-(3-(4-fluorophenyl)ureido)azetidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(3-(-chloro-2-fluorobenzamido)azetidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-ethylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-morpholinopropyl)hexanoic acid;
2-amino-6-borono-2-(3-thiomorpholinopropyl)hexanoic acid;
2-amino-6-borono-2-(3-(thiazolidin-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(phenethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(methyl(phenethyl)aminopropyl)hexanoic acid;
2-amino-6-borono-2-(3-(ethyl(naphthalen-1-ylmethyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(methyl(naphthalen-1-ylmethyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((cyclohexylmethyl)(ethyl)amino)propyl)hexanoic acid;
2-amino-2-(3-(benzyl(ethyl)amino)propyl)-6-boronohexanoic acid;
2-amino-2-(3-(benzyl(ethyl)amino)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-((4-chlorobenzyl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3,4-dichlorobenzyl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3,4-dichlorobenzyl)(ethyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(cyclohexylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(cyclohexyl(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(methyl(tetrahydro-2H-pyran-4-yl)amino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(cyclopentyl(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3-chlorobenzyl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((6-fluorochroman-4-yl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-methoxyethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((2-methoxyethyl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((S)-1-methoxypropan-2-ylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(dimethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((2-(dimethylamino)ethyl(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(dimethylamino)ethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(diethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((1R,4R)-5-(3,4-dichlorophenylcarbamoyl)-2,5-diazabicyclo[2.2.2]heptan-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-((S)-3-methyl-2-4((R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[α]phenathren-17-yl)pentanamido)butanoyloxy)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(4-(piperazin-1-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(4-(4-(3,4-dichlorophenyl)piperazin-1-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(4-(4-(3,4-difluorobenzyl)piperidin-1-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(4-(3,4-dihydroisoquinolin-2(1H)-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(4-(2-(4-fluorophenyl)piperidin-1-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(3-(carboxymethylamino)propyl)hexanoic acid;
2-amino-2-(3-(4-(biphenyl-4-ylmethyl)piperazin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-2-(3-(4-benzhydrylpiperazin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(4-(4-fluorobenzoyl)piperidin-1-yl)propyl)hexanoic acid;
2-(3-(3-(1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)propyl)-2-amino-6-boronohexanoic acid;
2-amino-6-borono-2(3-(4-(phenylamino)piperdin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-dichlorobenzylamino)piperidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-((3,4-dichlorobenzyl)(ethyl)amino)piperidin-1-yl) propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-methylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-fluoro-4-phenylpiperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(N-(3,4-dichlorobenzyl)octanamido)piperidin-1-yl)propyl)hexanoic acid;
2-amino-3-(3-(4-benzyl-4-(decanoyloxy)piperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-2-(3-(3-(benzo[d]oxazol-2-yl)piperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(2-phenylpyrrolin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-(3-(3,4-dichlorophenyl)ureido)pyrrolidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(3-(3-(4-fluorophenyl)ureido)pyrrolidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(3-(3,4-dichlorophenylsulfonamido)pyrrolidin-1-yl) propyl)hexanoic acid;
2-(3-(1H-imidazol-1-yl)propyl)-2-amino-6-boronohexanoic acid;
2-(3-(1H-benzo[d]imidazol-1-yl)propyl)-2-amino-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(cyclopentylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(tetrahydro-2H-pyran-4-ylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3R)-3-methoxytetrahydro-2H-pyran-4-ylamino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(methyl(naphthalen-2-ylmethyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(methyl((4-methylnaphthalen-1-yl)methyl)amino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-((4-(3,4-dichlorophenoxy)benzyl)(methyl)amino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-((3′,4′-dichlorobiphenyl-4-yl)methyl)(methyl)amino) propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3′,4′-dichlorobiphenyl)-4-yl)methylamino)propyl) hexanoic acid;
(S)-2-amino-6-borono-2-(3-(1-carboxylethylamino)propyl)hexanoic acid;
(S)-2-amino-6-borono-2-(3-(1-carboxy-3-methylbutylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((S)-1-methoxy-1-oxopropan-2-ylamino)propyl)hexanoic acid;
(S)-2-amino-6-borono-2-(3-(1-methoxy-4-methyl-1-oxopentan-2-ylamino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-dichlorobenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-methoxybenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3-methoxybenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-methylbenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-fluorobenzoyl)piperazin-1yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-fluorobenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-chlorobenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3-fluorobenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-4-(trifluoromethyl)benzoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-4-carbamoylbenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-3,4-dichlorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-2-fluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3-fluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-4-fluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3,4-difluorophenylcarbamoyl)piperazin-1-yl)propyl hexanoic acid;
2-amino-6-borono-2-(3-(4-2,5-difluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-2,4-difluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-2,3-difluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3,5-difluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-tosylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-4-fluorophenylsulfonyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3-fluorophenylsulfonyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3,4-dichlorophenylsulfonyl)piperazin-1-yl)propyl) hexanoic acid;
a salt thereof, an ester thereof and a mixture thereof.

147 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/191,160Filed 26 Jul 2011 · us provisional application
Priority: 31 Dec 2010
Published: US 2012/0171116 A15 Jul 2012
Granted: 25 Nov 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification45 codes

C07F 5/025
Boron compounds: boronic and borinic acid compounds
A61K 31/69
Medicinal preparations containing organic active ingredients: boron compounds
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…

Family

Application61/428,894Us provisional application · filed 31 Dec 2010
Application61/450,804Us provisional application · filed 9 Mar 2011
US 2012/0171116 A1Pre-grant publication · published 5 Jul 2012
US 8,894,970 B2This patent

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

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Abstract

A compound selected from the group consisting of:

2-amino-6-borono-2-(2-(piperazin-1-yl)ethyl)hexanoic acid;
2-amino-2-(3-(4-benzylpiperazin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(4-(2-chlorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-cyanobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2,4-difluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2,3-difluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-dichlorobenzyl)piperazin-1-yl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3-(trifluoromethyl)benzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-(methylsulfonyl)benzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-fluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-difluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,5-difluorobenzyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-phenethylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(2-(4-(3,4-dichlorobenzyl)piperazin-1-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-dichlorophenyl)piperazin-1yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(4-fluorophenyl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(2-(piperidin-2-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(2-(1-(3,4-dichlorobenzyl)piperidin-2-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(2-(1-(3,5-difluorobenzyl)piperidin-2-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(2-(1-(3,4-difluorobenzyl)piperidin-2-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(2-(1-(3,4-dichlorobenzyl)piperidin-3-yl)ethyl)hexanoic acid;
2-amino-6-borono-2-(3-(1-(3,4-dichlorobenzyl)piperidin-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(1-(3,4-difluorobenzyl)piperidin-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(1-(3,5-difluorobenzyl)piperidin-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-phenylpiperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-(5-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-difluorobenzyl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(pyrimidin-2-ylmethyl)piperidin-1-yl)propyl)hexanoic acid;
2-(3-(3H-spiro[isobenzofuran-1,4′piperidine]-1′-yl)propyl)-2-amino-6-boronohexanoic acid;
2-amino-6-borono-2(3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-chlorophenyl)-1H-pyrazol-1-yl)piperidin-1-yl) propylhexanoic acid;
2-amino-6-borono-2-(3-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-isopropylphenoxy)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-fluorophenyl)piperidin-1-yl)propylhexanoic acid;
2-amino-6-borono-2-(3-(4-(4-methoxyphenyl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)propyl) hexanoic acid;
2-amino-2-(3-(4-benzyl-4-hydroxypiperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-hydroxypiperidin-1-yl)propyl)hexanoic acid;
2-amino-2-(3-(4-((S)-2-amino-3-methylbutanoyloxy)piperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-2-(3-(4-benzamidopiperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-methyl-2-phenylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-2-(3-(2-benzylpiperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(2-(4-methoxyphenyl)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(3-methoxylphenyl)pyrrolidin-1l-yl)propyl)hexanoic acid 2-amino-6-borono-2-(3-(2-(2-fluorobenzyl)pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(2-(trifluoromethyl)phenyl)pyrrolidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(2-(4-fluorophenyl)pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(3-chlorophenyl)pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-2-(3-(2-(biphenyl-4-yl)pyrrolidin-1-yl)propyl)-6-borono-hexanoic acid;
2-amino-6-borono-2-(3-(2-(3,4-dichlorophenyl)pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(pyrrolidin-1-yl)propyl)hexanoic acid;
2-amino-2-(3-(azetidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(3-phenylazetidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-p-tolylazetidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-(3-(3,4-dichlorophenyl)ureido)azetidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(3-(3-(4-fluorophenyl)ureido)azetidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(3-(-chloro-2-fluorobenzamido)azetidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-ethylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-morpholinopropyl)hexanoic acid;
2-amino-6-borono-2-(3-thiomorpholinopropyl)hexanoic acid;
2-amino-6-borono-2-(3-(thiazolidin-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(phenethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(methyl(phenethyl)aminopropyl)hexanoic acid;
2-amino-6-borono-2-(3-(ethyl(naphthalen-1-ylmethyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(methyl(naphthalen-1-ylmethyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((cyclohexylmethyl)(ethyl)amino)propyl)hexanoic acid;
2-amino-2-(3-(benzyl(ethyl)amino)propyl)-6-boronohexanoic acid;
2-amino-2-(3-(benzyl(ethyl)amino)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-((4-chlorobenzyl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3,4-dichlorobenzyl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3,4-dichlorobenzyl)(ethyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(cyclohexylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(cyclohexyl(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(methyl(tetrahydro-2H-pyran-4-yl)amino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(cyclopentyl(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3-chlorobenzyl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((6-fluorochroman-4-yl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-methoxyethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((2-methoxyethyl)(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((S)-1-methoxypropan-2-ylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(dimethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((2-(dimethylamino)ethyl(methyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(2-(dimethylamino)ethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(diethylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((1R,4R)-5-(3,4-dichlorophenylcarbamoyl)-2,5-diazabicyclo[2.2.2]heptan-2-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-((S)-3-methyl-2-4((R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[α]phenathren-17-yl)pentanamido)butanoyloxy)piperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(4-(piperazin-1-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(4-(4-(3,4-dichlorophenyl)piperazin-1-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(4-(4-(3,4-difluorobenzyl)piperidin-1-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(4-(3,4-dihydroisoquinolin-2(1H)-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(4-(2-(4-fluorophenyl)piperidin-1-yl)butyl)hexanoic acid;
2-amino-6-borono-2-(3-(carboxymethylamino)propyl)hexanoic acid;
2-amino-2-(3-(4-(biphenyl-4-ylmethyl)piperazin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-2-(3-(4-benzhydrylpiperazin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(4-(4-fluorobenzoyl)piperidin-1-yl)propyl)hexanoic acid;
2-(3-(3-(1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)propyl)-2-amino-6-boronohexanoic acid;
2-amino-6-borono-2(3-(4-(phenylamino)piperdin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-dichlorobenzylamino)piperidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-((3,4-dichlorobenzyl)(ethyl)amino)piperidin-1-yl) propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-methylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-fluoro-4-phenylpiperidin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(N-(3,4-dichlorobenzyl)octanamido)piperidin-1-yl)propyl)hexanoic acid;
2-amino-3-(3-(4-benzyl-4-(decanoyloxy)piperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-2-(3-(3-(benzo[d]oxazol-2-yl)piperidin-1-yl)propyl)-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(2-phenylpyrrolin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(3-(3-(3,4-dichlorophenyl)ureido)pyrrolidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(3-(3-(4-fluorophenyl)ureido)pyrrolidin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(3-(3,4-dichlorophenylsulfonamido)pyrrolidin-1-yl) propyl)hexanoic acid;
2-(3-(1H-imidazol-1-yl)propyl)-2-amino-6-boronohexanoic acid;
2-(3-(1H-benzo[d]imidazol-1-yl)propyl)-2-amino-6-boronohexanoic acid;
2-amino-6-borono-2-(3-(cyclopentylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(tetrahydro-2H-pyran-4-ylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3R)-3-methoxytetrahydro-2H-pyran-4-ylamino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(methyl(naphthalen-2-ylmethyl)amino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(methyl((4-methylnaphthalen-1-yl)methyl)amino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-((4-(3,4-dichlorophenoxy)benzyl)(methyl)amino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-((3′,4′-dichlorobiphenyl-4-yl)methyl)(methyl)amino) propyl)hexanoic acid;
2-amino-6-borono-2-(3-((3′,4′-dichlorobiphenyl)-4-yl)methylamino)propyl) hexanoic acid;
(S)-2-amino-6-borono-2-(3-(1-carboxylethylamino)propyl)hexanoic acid;
(S)-2-amino-6-borono-2-(3-(1-carboxy-3-methylbutylamino)propyl)hexanoic acid;
2-amino-6-borono-2-(3-((S)-1-methoxy-1-oxopropan-2-ylamino)propyl)hexanoic acid;
(S)-2-amino-6-borono-2-(3-(1-methoxy-4-methyl-1-oxopentan-2-ylamino)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-(3,4-dichlorobenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-methoxybenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3-methoxybenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-methylbenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(4-fluorobenzoyl)piperazin-1yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-fluorobenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(2-chlorobenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-(3-fluorobenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-4-(trifluoromethyl)benzoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-4-carbamoylbenzoyl)piperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-3,4-dichlorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-2-fluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3-fluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-4-fluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3,4-difluorophenylcarbamoyl)piperazin-1-yl)propyl hexanoic acid;
2-amino-6-borono-2-(3-(4-2,5-difluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-2,4-difluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-2,3-difluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3,5-difluorophenylcarbamoyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-tosylpiperazin-1-yl)propyl)hexanoic acid;
2-amino-6-borono-2-(3-(4-4-fluorophenylsulfonyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3-fluorophenylsulfonyl)piperazin-1-yl)propyl) hexanoic acid;
2-amino-6-borono-2-(3-(4-3,4-dichlorophenylsulfonyl)piperazin-1-yl)propyl) hexanoic acid;
a salt thereof, an ester thereof and a mixture thereof.

147 more elements

Facts

Application

13/191,160Filed 26 Jul 2011 · us provisional application

Priority

31 Dec 2010

Published

US 2012/0171116 A15 Jul 2012

Granted

25 Nov 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification45 codes

C07F 5/025
Boron compounds: boronic and borinic acid compounds
A61K 31/69
Medicinal preparations containing organic active ingredients: boron compounds
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…