US 8,524,717 B2Granted

Oxidase inhibitors and their use

AssigneeOryzon Genomics, S.A.

InventorsNathalie Guibourt, Alberto Ortega Munoz, Julio Castro-Palomino Laria

Life of this patent

Estimating the term…

Abstract

The invention relates to phenylcyclopropylamine acetamide derivatives and their use in treating diseases.

Claims31

Dependent claims

A compound of Formula I or a pharmaceutically acceptable salt thereof:

wherein each of R1-R5 is optionally substituted and independently chosen from —H, halo, alkyl, alkoxy, cycloalkoxy, haloalkyl, haloalkoxy, -L-aryl, -L-heteroaryl, -L-heterocyclyl, -L-carbocycle, acylamino, acyloxy, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, cyano, cyanato, haloaryl, hydroxyl, heteroaryloxy, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido;
R6 is chosen from —H and alkyl;
R7 is chosen from —H, alkyl, and cycloalkyl;
R8 is chosen from —C(═O)NRxRy and —C(═O)Rz;
Rx when present is chosen from —H, alkyl, alkynyl, alkenyl, -L-carbocycle, and -L-heterocyclyl, all of which are optionally substituted;
Ry when present is chosen from —H, alkyl, alkynyl, alkenyl, -L-carbocycle, -L-aryl, and -L-heterocyclyl, all of which are optionally substituted;
Rz when present is chosen from —H, alkoxy, -L-carbocycle, -L-heterocyclyl, and -L-aryl, wherein the aryl, heterocyclyl or carbocycle is optionally substituted;
each L can be saturated, partially saturated, or unsaturated, and is independently chosen from —(CH2)n—(CH2)n—, —(CH2)nC(═O)(CH2)n—, —(CH2)nC(═O)NH(CH2)n—, —(CH2)nNHC(═O)O(CH2)n—, —(CH2)nNHC(═O)NH(CH2)n—, —(CH2)nNHC(═S)S(CH2)n—, —(CH2)nOC(═O)S(CH2)n—, —(CH2)nNH(CH2)n—, —(CH2)nO(CH2)n—, —(CH2)nS(CH2)n—, and —(CH2)nNHC(═S)NH(CH2)n—, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein optionally substituted refers to zero or 1 to 4 optional substituents independently chosen from acylamino, acyloxy, alkenyl, alkoxy, cycloalkoxy, alkyl, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, carbocyclyl, cyano, cyanato, halo, haloalkyl, haloaryl, hydroxyl, heteroaryl, heteroaryloxy, heterocyclyl, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

5 more elements

A compound of Formula I or a pharmaceutically acceptable salt thereof:

wherein R3 is an optionally substituted aryl group having from 1-4 optional substituents;
each of R1, R2, R4 and R5 is optionally substituted and independently chosen from —H, halo, alkyl, alkoxy, cycloalkoxy, haloalkyl, haloalkoxy, -L-aryl, -L-heteroaryl, -L-heterocyclyl, -L-carbocycle, acylamino, acyloxy, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, cyano, cyanato, haloaryl, hydroxyl, heteroaryloxy, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido;
R6 is chosen from —H and alkyl;
R7 is chosen from —H, alkyl, and cycloalkyl;
R8 is chosen from —C(═O)NRxRy and —C(═O)Rz;
Rx when present is chosen from alkynyl, alkenyl, -L-carbocycle, -L-aryl, and -L-heterocyclyl, all of which are optionally substituted;
Ry when present is chosen from —H, alkyl, alkynyl, alkenyl, -L-carbocycle, -L-aryl, and -L-heterocyclyl, all of which are optionally substituted;
Rz when present is chosen from —H, alkoxy, -L-carbocycle, -L-heterocyclyl, and -L-aryl, wherein the aryl, heterocyclyl or carbocycle is optionally substituted;
each L can be saturated, partially saturated, or unsaturated, and is independently chosen from —(CH2)n—(CH2)n—, —(CH2)nC(═O)(CH2)n—, —(CH2)nC(═O)NH(CH2)n—, —(CH2)nNHC(═O)O(CH2)n—, —(CH2)nNHC(═O)NH(CH2)n—, —(CH2)nNHC(═S)S(CH2)n—, —(CH2)nOC(═O)S(CH2)n—, —(CH2)nNH(CH2)n—, —(CH2)nO(CH2)n—, —(CH2)nS(CH2)n—, and —(CH2)nNHC(═S)NH(CH2)n—, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein optionally substituted refers to zero or 1 to 4 optional substituents independently chosen from acylamino, acyloxy, alkenyl, alkoxy, cycloalkoxy, alkyl, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, carbocyclyl, cyano, cyanato, halo, haloalkyl, haloaryl, hydroxyl, heteroaryl, heteroaryloxy, heterocyclyl, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

6 more elements

A compound of Formula I or a pharmaceutically acceptable salt thereof:

wherein R3 is an optionally substituted arylalkoxy group having from 1-4 optional substituents;
each of R1, R2, R4 and R5 is optionally substituted and independently chosen from —H, halo, alkyl, alkoxy, cycloalkoxy, haloalkyl, haloalkoxy, -L-aryl, -L-heteroaryl, -L-heterocyclyl, -L-carbocycle, acylamino, acyloxy, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, cyano, cyanato, haloaryl, hydroxyl, heteroaryloxy, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido;
R6 is chosen from —H and alkyl;
R7 is chosen from —H, alkyl, and cycloalkyl;
R8 is chosen from —C(═O)NRxRy and —C(═O)Rz;
Rx is chosen from —H, alkyl, alkynyl, alkenyl, -L-carbocycle, -L-aryl, and -L-heterocyclyl, all of which are optionally substituted;
Ry when present is chosen from —H, alkyl, alkynyl, alkenyl, -L-carbocycle, -L-aryl, and -L-heterocyclyl, all of which are optionally substituted;
Rz when present is chosen from —H, alkoxy, -L-carbocycle, -L-heterocyclyl, and -L-aryl, wherein the aryl, heterocyclyl or carbocycle is optionally substituted;
each L can be saturated, partially saturated, or unsaturated, and is independently chosen from —(CH2)n—(CH2)n—, —(CH2)nC(═O)(CH2)n—, —(CH2)nC(═O)NH(CH2)n—, —(CH2)nNHC(═O)O(CH2)n—, —(CH2)nNHC(═O)NH(CH2)n—, —(CH2)nNHC(═S)S(CH2)n—, —(CH2)nOC(═O)S(CH2)n—, —(CH2)nNH(CH2)n—, —(CH2)nO(CH2)n—, —(CH2)nS(CH2)n—, and —(CH2)nNHC(═S)NH(CH2)n—, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein optionally substituted refers to zero or 1 to 4 optional substituents independently chosen from acylamino, acyloxy, alkenyl, alkoxy, cycloalkoxy, alkyl, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, carbocyclyl, cyano, cyanato, halo, haloalkyl, haloaryl, hydroxyl, heteroaryl, heteroaryloxy, heterocyclyl, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

6 more elements

A compound of Formula I or a pharmaceutically acceptable salt thereof:

wherein
each of R1-R5 is optionally substituted and independently chosen from —H, halo, alkyl, alkoxy, cycloalkoxy, haloalkyl, haloalkoxy, -L-aryl, -L-heteroaryl, -L-heterocyclyl, -L-carbocycle, acylamino, acyloxy, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, cyano, cyanato, haloaryl, hydroxyl, heteroaryloxy, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido;
R6 is chosen from —H and alkyl;
R7 is chosen from —H, alkyl, and cycloalkyl;
R8 is chosen from —C(═O)NRxRy and —C(═O)Rz;
Rx when present is chosen from —H, alkyl, alkynyl, alkenyl, -L-carbocycle, -L-aryl, and -L-heterocyclyl, all of which are optionally substituted;
Ry when present is chosen from —H, —CH(CH3)2, —C(CH3)3, —CH2C≡CH, —CH2CH═CH2, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and —CH2(phenyl), wherein the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and phenyl group is optionally substituted;
Rz when present is chosen from —H, alkoxy, -L-carbocycle, -L-heterocyclyl, and -L-aryl, wherein the aryl, heterocyclyl or carbocycle is optionally substituted;
each L can be saturated, partially saturated, or unsaturated, and is independently chosen from —(CH2)n—(CH2)n—, —(CH2)nC(═O)(CH2)n—, —(CH2)nC(═O)NH(CH2)n—, —(CH2)nNHC(═O)O(CH2)n—, —(CH2)nNHC(═O)NH(CH2)n—, —(CH2)nNHC(═S)S(CH2)n—, —(CH2)nOC(═O)S(CH2)n—, —(CH2)nNH(CH2)n—, —(CH2)nO(CH2)n—, —(CH2)nS(CH2)n—, and —(CH2)nNHC(═S)NH(CH2)n—, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein optionally substituted refers to zero or 1 to 4 optional substituents independently chosen from acylamino, acyloxy, alkenyl, alkoxy, cycloalkoxy, alkyl, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, carbocyclyl, cyano, cyanato, halo, haloalkyl, haloaryl, hydroxyl, heteroaryl, heteroaryloxy, heterocyclyl, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

6 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/066,616Filed 18 Apr 2011 · continuation
Priority: EP 0816697317 Oct 2008
Published: US 2011/0263604 A127 Oct 2011
Granted: 3 Sep 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07C 237/04
Having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton: the carbon skeleton being acyclic and…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
A61P 35/00
Antineoplastic agents
C07C 229/14
The nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic…

Family

PCT/EP2009/063685Parent of this continuation · filed 19 Oct 2009
US 2011/0263604 A1Pre-grant publication · published 27 Oct 2011
US 8,524,717 B2This patent

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

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A compound of Formula I or a pharmaceutically acceptable salt thereof:

wherein each of R1-R5 is optionally substituted and independently chosen from —H, halo, alkyl, alkoxy, cycloalkoxy, haloalkyl, haloalkoxy, -L-aryl, -L-heteroaryl, -L-heterocyclyl, -L-carbocycle, acylamino, acyloxy, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, cyano, cyanato, haloaryl, hydroxyl, heteroaryloxy, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido;
R6 is chosen from —H and alkyl;
R7 is chosen from —H, alkyl, and cycloalkyl;
R8 is chosen from —C(═O)NRxRy and —C(═O)Rz;
Rx when present is chosen from —H, alkyl, alkynyl, alkenyl, -L-carbocycle, and -L-heterocyclyl, all of which are optionally substituted;
Ry when present is chosen from —H, alkyl, alkynyl, alkenyl, -L-carbocycle, -L-aryl, and -L-heterocyclyl, all of which are optionally substituted;
Rz when present is chosen from —H, alkoxy, -L-carbocycle, -L-heterocyclyl, and -L-aryl, wherein the aryl, heterocyclyl or carbocycle is optionally substituted;
each L can be saturated, partially saturated, or unsaturated, and is independently chosen from —(CH2)n—(CH2)n—, —(CH2)nC(═O)(CH2)n—, —(CH2)nC(═O)NH(CH2)n—, —(CH2)nNHC(═O)O(CH2)n—, —(CH2)nNHC(═O)NH(CH2)n—, —(CH2)nNHC(═S)S(CH2)n—, —(CH2)nOC(═O)S(CH2)n—, —(CH2)nNH(CH2)n—, —(CH2)nO(CH2)n—, —(CH2)nS(CH2)n—, and —(CH2)nNHC(═S)NH(CH2)n—, where each n is independently chosen from 0, 1, 2, 3, 4, 5, 6, 7, and 8, wherein optionally substituted refers to zero or 1 to 4 optional substituents independently chosen from acylamino, acyloxy, alkenyl, alkoxy, cycloalkoxy, alkyl, alkylthio, cycloalkylthio, alkynyl, amino, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylalkoxy, aryloxy, arylthio, heteroarylthio, carbocyclyl, cyano, cyanato, halo, haloalkyl, haloaryl, hydroxyl, heteroaryl, heteroaryloxy, heterocyclyl, heteroarylalkoxy, isocyanato, isothiocyanato, nitro, sulfinyl, sulfonyl, sulfonamide, thiocarbonyl, thiocyanato, trihalomethanesulfonamido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, and C-amido.

5 more elements

Facts

Application

13/066,616Filed 18 Apr 2011 · continuation

Priority

EP 0816697317 Oct 2008

Published

US 2011/0263604 A127 Oct 2011

Granted

3 Sep 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07C 237/04
Having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton: the carbon skeleton being acyclic and…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
A61P 35/00
Antineoplastic agents
C07C 229/14
The nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic…