Back to results
US 2009/0023708 A1Published application
Compounds Comprising a Lactam or a Lactam Derivative Moiety, Processes for Making Them, and Their Uses
AssigneeUCB Pharma S.A.
InventorsSylvain Celanire, Luc Quere, Frederic Denonne, Laurent Provins
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of formula (I) comprising a lactam or a lactam derivative moiety, processes for preparing them, pharmaceutical compositions comprising said compounds and their uses as pharmaceuticals.
Claims48
A compound of formula (I), geometrical isomers, enantiomers, diastereoisomers, pharmaceutically acceptable salts and all possible mixtures thereof,
- wherein
- A1 is CH, C-halogen or N;
- A2 is oxygen or sulfur;
- R1 is hydrogen;
- R2a is hydrogen, aryl, C1-6 alkoxy, amino, C1-6 alkyl, C2-6 alkenyl, heteroaryl, C3-8 cycloalkyl, 3-8-membered heterocycloalkyl, acyl, C1-6-alkyl aryl, C1-6-alkyl heteroaryl, C1-6-alkyl cycloalkyl, C1-6-alkyl heterocycloalkyl, carboxy, alkoxycarbonyl, aminocarbonyl, C1-6-alkyl carboxy, C1-6-alkyl acyl, C1-6-alkyl alkoxy, C1-6-alkyl alkoxycarbonyl, C1-6-alkyl aminocarbonyl, C1-6-alkyl acylamino, acylamino, C1-6-alkyl ureido, C1-6-alkyl carbamate, C1-6-alkyl amino, C3-8-cycloalkyl amino, hydroxy, C1-6 alkyl hydroxy, halogen or cyano;
- R2b is hydrogen, halogen, C1-8-alkyl or C3-8 cycloalkyl;
- or R2a and R2b are linked together to form a C3-8 cycloalkyl, a 3-8-membered heterocycloalkyl or an oxo group;
- R3 is hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy;
- R4 is hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy or —O—(CH2)t—NR7aR7b;
- R5 is hydrogen or —O—(CH2)w—NR8aR8b;
- L1 is (O)v—(CR9aR9b)m—(CH2)z;
- R7a and R7b are linked together to form with N a 3 to 8 membered heterocycloalkyl;
- R8a and R8b are linked together to form with N a 3 to 8 membered heterocycloalkyl;
- R9a is hydrogen or unsubstituted C1-8 alkyl;
- R9b is a C1-6-alkyl aryl or unsubstituted C1-8 alkyl;
- n is an integer equal to 0, 1 or 2;
- t is an integer equal to 2, 3 or 4;
- w is an integer equal to 2, 3 or 4;
- v is an integer equal to 0 or 1;
- m is an integer equal to 0 or 1;
- z is an integer equal to 0, 1, 2 or 3;
- provided that
- at least one of m and z is different from 0;
- and that
- R4 is —O—(CH2)t—NR7aR7b, when R5 is hydrogen;
- and
- R5 is —O—(CH2)w—NR8aR8b, when R4 is hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy;
- and
- that compound of formula (I) is different from 1-[4-[2-(pyrrolidin-1-yl)ethoxy]phenyl]pyrrolidin-2-one, 1-[4-[2-[4-(2-methylphenyl)-1-piperazinyl]ethoxy]phenyl]-pyrrolidin-2-one and 3-(p-2-morpholinoethoxyphenyl)-oxazolidin-2-one.
26 more elements
(canceled)
(canceled)
A compound of formula (III), geometrical isomers, enantiomers, diastereoisomers, pharmaceutically acceptable salts and all possible mixtures thereof,
- wherein
- A2 is an oxygen or a sulfur atom;
- R2a is (CH2)r—NR6aR6b;
- R2b is hydrogen;
- or R2a and R2b are linked together to form a C2-6 alkylene, one methylene being optionally replaced by a nitrogen atom, said nitrogen atom being optionally substituted by a C1-6-alkyl aryl or an acyl;
- L1 is —(O)v—(CR9aR9b)m—(CH2)z;
- R6a is hydrogen, C1-8 alkyl, C1-6-alkyl cycloalkyl, C3-8 cycloalkyl, acyl, aryl or C1-6-alkyl aryl;
- R6b is hydrogen, C1-4 alkyl, C1-6-alkyl cycloalkyl or C1-6-alkyl aryl;
- or R6a and R6b are linked together to form a C3-6 alkylene, each methylene of the alkylene being optionally substituted by one or two halogen, or by one or two C1-4 alkyl, optionally linked together to form with the carbon to which they are attached a C3-8 cycloalkyl;
- or one methylene thereof being linked to a second methylene thereof to form a C3-6 alkylene;
- or one methylene being optionally replaced by sulfur dioxide, an oxygen, a sulfur or a nitrogen atom, said nitrogen atom being optionally substituted by a C1-8 alkyl or C3-8 cycloalkyl;
- R9a is hydrogen or unsubstituted C1-8 alkyl;
- R9b is unsubstituted C1-8 alkyl;
- n is an integer equal to 0 or 1;
- r is an integer equal to 1 or 2;
- v and m are independently an integer equal to 0 or 1;
- z is an integer comprised between 0 and 3;
- and at least one of m and z is different from 0.
15 more elements
A compound of formula (X), geometrical isomers, enantiomers, diastereoisomers, pharmaceutically acceptable salts and all possible mixtures thereof,
- wherein
- A1 is CH, C-halogen or N;
- A2 is oxygen or sulfur;
- R1 is hydrogen;
- R2b is hydrogen;
- R3 is hydrogen, halogen or C1-4 alkoxy;
- R4 is hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy or —O—(CH2)t—NR7aR7b;
- R5 is hydrogen or —O—(CH2)w—NR8aR8b;
- L1 is (O)v—(CR9aR9b)m—(CH2)z;
- R7a and R7b are linked together to form a C3-6 alkylene, each methylene of the alkylene being optionally substituted by one or two C1-4 alkyl;
- R8a and R8b are linked together to form a C3-6 alkylene, each methylene of the alkylene being optionally substituted by one or two C1-4 alkyl optionally linked together to form with the carbon to which they are attached a C3-8 cycloalkyl, by C1-6 alkyl hydroxy, aryl or C1-6 alkyl aryl;
- or one methylene thereof being linked to a second methylene thereof to form a C3-6 alkylene;
- or one methylene of the alkylene being optionally replaced by a nitrogen, said nitrogen being substituted by a C1-4 alkyl or C3-8 cycloalkyl;
- R9a is hydrogen or an unsubstituted C1-8 alkyl;
- R9b is an unsubstituted C1-8 alkyl;
- R14 is —(CH2)r—Cl, —COOR15 or C1-7 alkyl substituted by —COOR15;
- R15 is hydrogen or C1-4 alkyl;
- n is an integer equal to 0 or 1;
- r is an integer equal to 1 or 2;
- t and w are independently an integer comprised between 2 and 4;
- v and m are independently an integer equal to 0 or 1;
- z is an integer comprised between 0 and 3;
- provided that
- at least one of m and z is different from 0;
- and that
- R4 is —O—(CH2)t—NR7aR7b, when R5 is hydrogen;
- and
- R5 is —O—(CH2)w—NR8aR8b, when R4 is hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy.
25 more elements
A compound selected from the group consisting of
- (5S)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one;
- (5R)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one;
- (5S)-5-[(2-methylpiperidin-1-yl)methyl]pyrrolidin-2-one;
- (5S)-5-[(2,6-dimethylpiperidin-1-yl)methyl]pyrrolidin-2-one;
- (5S)-5-[(4-methylpiperidin-1-yl)methyl]pyrrolidin-2-one;
- (5S)-5-[(2-methylpyrrolidin-1-yl)methyl]pyrrolidin-2-one;
- (5S)-5-{[(2R)-2-methylpyrrolidin-1-yl]methyl}pyrrolidin-2-one;
- (5S)-5-{[(2S)-2-methylpyrrolidin-1-yl]methyl}pyrrolidin-2-one;
- (5S)-5-(pyrrolidin-1-ylmethyl)pyrrolidin-2-one;
- (5S)-5-(azepan-1-ylmethyl)pyrrolidin-2-one;
- (5S)-5-[(4-cyclopentylpiperazin-1-yl)methyl]pyrrolidin-2-one;
- (5S)-5-{[4-(cyclohexylmethyl)piperazin-1-yl]methyl}pyrrolidin-2-one;
- (5S)-5-[(4-isopropylpiperazin-1-yl)methyl]pyrrolidin-2-one;
- (5S)-5-{[(cyclopropylmethyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-{[(cyclohexylmethyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-[(cyclobutylamino)methyl]pyrrolidin-2-one;
- (5S)-5-[(cyclopentylamino)methyl]pyrrolidin-2-one;
- (5S)-5-[(cyclohexylamino)methyl]pyrrolidin-2-one;
- (5S)-5-{[(cyclopropylmethyl)(propyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-{[(4-fluorobenzyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-(anilinomethyl)pyrrolidin-2-one;
- (5S)-5-{[(4-fluorophenyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-{[(2-fluorophenyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-{[(3-fluorophenyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-{[(2,4-difluorophenyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-{[(3-methoxyphenyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-({[4-(trifluoromethyl)phenyl]amino}methyl)pyrrolidin-2-one;
- (5S)-5-[(4-fluorophenoxy)methyl]pyrrolidin-2-one;
- (5S)-5-{[(4-methylphenyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-{[(3,4-difluorophenyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-{[(3,5-difluorophenyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-[(3,4-difluorophenoxy)methyl]pyrrolidin-2-one;
- (5S)-5-[(1,3-benzodioxol-5-ylamino)methyl]pyrrolidin-2-one;
- (5S)-5-{[(4-fluorophenyl)(methyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-(thiomorpholin-4-ylmethyl)pyrrolidin-2-one;
- (5S)-5-[(4,4-difluoropiperidin-1-yl)methyl]pyrrolidin-2-one;
- (5S)-5-{[(2,2,2-trifluoroethyl)amino]methyl}pyrrolidin-2-one;
- (5S)-5-[(4aS,8aS)-octahydroisoquinolin-2(1H)-ylmethyl]pyrrolidin-2-one;
- (5S)-5-{[cis-2,6-dimethylmorpholin-4-yl]methyl}pyrrolidin-2-one;
- (4R)-4-{[cis-2,6-dimethylmorpholin-4-yl]methyl}-1,3-oxazolidin-2-one;
- (4R)-4-(piperidin-1-ylmethyl)-1,3-oxazolidin-2-one;
- (4R)-4-[(4,4-difluoropiperidin-1-yl)methyl]-1,3-oxazolidin-2-one;
- (4R)-4-[(dibenzylamino)methyl]-1,3-oxazolidin-2-one;
- (4R)-4-{[(3,4-difluorophenyl)amino]methyl}-1,3-oxazolidin-2-one;
- (4S)-4-(piperidin-1-ylmethyl)azetidin-2-one;
- 7-benzyl-2,7-diazaspiro[4.4]nonan-3-one;
- 4-(pyrrolidin-1-ylmethyl)-1,3-oxazolidin-2-one;
- 4-(4-chlorobenzyl)-1,3-oxazolidin-2-one;
- (5S)-5-[(1,1-dioxidothiomorpholin-4-yl)methyl]pyrrolidin-2-one;
- (5S)-3,3-dimethyl-5-(piperidin-1-ylmethyl)pyrrolidin-2-one;
- (5R)-5-{[cis-2,6-dimethylmorpholin-4-yl]methyl}-3,3-dimethylpyrrolidin-2-one;
- (5R)-5-[(4,4-difluoropiperidin-1-yl)methyl]-3,3-dimethylpyrrolidin-2-one;
- [(2S)-4-oxoazetidin-2-yl]methyl-4-methylbenzenesulfonate;
- methyl [1-benzyl-3-(nitromethyl)pyrrolidin-3-yl)acetate;
- methyl 1-[4-(3-chloropropoxy)phenyl]-5-oxopyrrolidine-3-carboxylate;
- methyl 1-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-5-oxopyrrolidine-3-carboxylate;
- ethyl (1-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-5-oxopyrrolidin-3-yl)acetate;
- 4-(chloromethyl)-1-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}pyrrolidin-2-one;
- 4-(2-chloroethyl)-1-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}pyrrolidin-2-one;
- 2-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-2,7-diazaspiro[4.4]nonan-3-one;
- and
- (5S)-1-(6-chloropyridin-3-yl)-5-(piperidin-1-ylmethyl)pyrrolidin-2-one.
59 more elements
(canceled)
Dependencies are inferred from the claim text.