3-Heterocyclylpropanohydroxamic acids
AssigneePfizer Products Inc.
InventorsSimon Bailey, Stephane Billotte, Paul Vincent Fish, Kim James, Nicholas Murray Thomson, Andrew Michael Derrick
Life of this patent
Estimating the term…
Abstract
Compound of formula (I): 1 and their salts, solvates, prodrugs, etc., wherein the substituents have the values mentioned herein, are Procollagen C-Proteinase (PCP) inhibitors and have utility in conditions mediated by PCP.
Claims53
A compound of formula (I):
- 202
- wherein:
- X is C1-6 alkylene or C2-6 alkenylene, each of which is optionally substituted by one or more fluorine atoms;
- R is aryl or C3-8 cycloalkyl optionally substituted by one or more fluorine atoms;
- W is N or CZ;
- Y and Z are each independently H, C1-4 alkyl (optionally substituted by one or more substituents independently selected from halogen, S(O)pR6, OR5, CONR1R2, CO2R7 and aryl), C1-4 alkanoyl optionally substituted by one or more halogen, C1-4 alkoxycarbonyl optionally substituted by one or more halogen, or CONR1R2;
- R1 and R2 are each independently selected from H, C3-8 cycloalkyl, C1-4 alkyl (optionally substituted by C3-8 cycloalkyl, aryl, CO2H, CO2R5 and/or NR3R4), or R1 and R2 can be taken together with the nitrogen to which they are attached to represent a 4- to 6-membered heterocyclic ring optionally containing one or two further hetero atoms in the ring independently selected from N, O and S, which heterocyclic ring is optionally benzo- or pyrido-fused, and which heterocyclic ring is optionally substituted by C1-4 alkyl, CO2H, CO2R5, aryl and/or NR3R4;
- R3 and R4 are each independently selected from H, C1-C4 alkyl or C1-4 alkoxycarbonyl optionally substituted by one or more halogen, or R3 and R4 can be taken together with the nitrogen atom to which they are attached to represent a morpholine, piperidine, azetidine or piperazine (optionally N-substituted by C1-4 alkyl) moiety;
- R5 is C1-4 alkyl optionally substituted by CO2R7 or CONR3R4, or R5 is aryl;
- R6 is C1-4 alkyl optionally substituted by one or more halogen, or aryl;
- R7 is H or R6;
- p is 0,1 or 2;
- “Aryl” is a mono- or bicyclic aromatic carbocyclic or heterocyclic system comprising from 5 to 10 ring atoms, including up to 3 hetero-atoms selected from N, O and S, where, if there is a N atom in the ring, it can be present as the N-oxide, which ring system is optionally substituted by up to 3 substituents independently selected from halogen, C1-4 alkyl optionally substituted by one or more halogen, C1-4 alkoxy optionally substituted by one or more halogen, phenyl, pyridyl, CO2H, CONR3R4, CO2(C1-4 alkyl), NR3R4, OH and OC(O)(C1-4 alkyl);
- and the pharmaceutically acceptable salts, solvates (including hydrates) and prodrugs thereof.
A compound, salt, solvate or prodrug according to any previous claim wherein W is N.
A compound, salt, solvate or prodrug according to any previous claim where X is a linear C2-4 alkylene moiety optionally substituted by one or more fluorine atoms.
A compound, salt, solvate or prodrug according to any previous claim where R is C3-8 cycloalkyl optionally substituted by one or more fluorine atoms.
A compound, salt, solvate or prodrug according to any previous claim where Y is C1-4 alkyl (optionally substituted by one or more substituents independently selected from halogen, S(O)pR6, OR5, CONR1R2, CO2R7 and aryl), C1-4 alkoxycarbonyl, or CONR1R2.
A compound, salt, solvate or prodrug according to any previous claim wherein X is propylene.
A compound, salt, solvate or prodrug according to any previous claim wherein R is cyclobutyl or cyclohexyl optionally substituted by one or more fluorine atoms.
A compound, salt, solvate or prodrug according to any previous claim wherein Y is methyl, isopropyl, methoxymethyl, 2-methoxyethyl, (pyrrolidino)COCH2, phenylsulphonylmethyl, 4-chlorophenoxymethyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (pyridin-4-yl)methyl, (imidazol-2-yl)methyl, CO2(C1-2 alkyl), CONH2, CONH(C1-4 alkyl (optionally substituted by C3-8 cycloalkyl, aryl, CO2H or CO2R5)), CON(C1-4 alkyl)(C1-4 alkyl(optionally substituted by C3-8 cycloalkyl, aryl, CO2H or CO2R5)), or CONR1R2 where R1 and R2 are taken together with the nitrogen to which they are attached to represent a 4- to 6-membered heterocyclic ring optionally containing one or two further hetero atoms in the ring independently selected from N, O and S, and which heterocyclic ring is optionally benzo- or pyrido-fused, and which heterocyclic ring is optionally substituted by C1-4 alkyl, CO2H, CO2R5, aryl or NR3R4.
A compound, salt, solvate or prodrug according to any previous claim wherein R is cyclobutyl or cyclohexyl.
A compound, salt, solvate or prodrug according to any previous claim wherein Y is CO2C2H5, CONH2, CONHCH3, CONH(n-C3H7), CONH(i-C3H7), (cyclopropyl)CH2NHCO, (cyclobutyl)CH2NHCO, (2-methoxyphenyl)CH2NHCO, (4-methoxyphenyl)CH2NHCO, (pyridin-2-yl)CH2NHCO, CONHCH2CO2H, CON(CH3)CH2CO2CH3, CON(CH3)2, (4-dimethylaminopiperidinyl)CO, (3-morpholinoazetidinyl)CO, (4-(pyridin-4-yl)piperidino)CO, (pyridin-2-yl)CH2N (CH3)CO, CON(CH3)CH2CO2H, (3-methoxycarbonylazetidinyl)CO, (3-carboxyazetidinyl)CO, methyl, isopropyl, methoxymethyl, 2-methoxyethyl, (pyrrolidino)COCH2, phenylsulphonylmethyl, 4-chlorophenoxymethyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (pyridin-4-yl)methyl, (imidazol-2-yl)methyl, benzylaminocarbonyl, piperidinocarbonyl, (2,3-dihydroisoindol-2-yl)CO, (1,2,3,4-tetrahydroisoquinolin-2-yl)CO, morpholinocarbonyl, 4-methylpiperazinocarbonyl, (5-aza-1,2,3,4-tetrahydroisoquinolin-2-yl)CO or N-methylbenzylaminocarbonyl.
A compound, salt, solvate or prodrug according to any previous claim wherein R is cyclohexyl.
A compound, salt, solvate or prodrug according to any previous claim wherein Y is CONH2, CONHCH3 or CON(CH3)2.
A PCP inhibitor which is selective against MMP-1 and/or MMP-2 and/or MMP-9 and/or MMP-14.
A substance according to any previous claim for use in medicine.
(2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid.
(4S)-4-benzyl-3-(5-cyclohexylpentanoyl)-1,3-oxazolidin-2-one.
tert-butyl 3-{[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-6-cyclohexylhexanoate
2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid.
3-(diethoxyphosphoryl)succinic acid 1-tert-butyl ester.
(E)-2-[2-(tert-butoxy)-2-oxoethyl]-5-phenyl-2-pentenoic acid.
(R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-phenylpentanoic acid.
(R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid cyclohexylamine salt.
Dependencies are inferred from the claim text.