Oxo or oxy-pyridine compounds as 5-HT4 receptor modulators
First Claim
1. Compounds of formula (I) and (II):
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or the pharmaceutically acceptable esters thereof, and the pharmaceutically acceptable salts thereof whereinR1 is hydrogen, halo, C1-6 alkyl, aryl or heteroaryl;
R2 and R3 are independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino(C1-5)alkyl or hydroxy(C1-5)alkyl;
or two of R2 and R3, or R3 and R4 taken together with the nitrogen atom to which they are attached may form a nitrogen-containing heterocycle selected from morpholino, piperazino, piperidino, pyrrolidino, azetidino, pyrazolidino, (1,2,3,4)-tetrahydroisoquinolino, or perhydroisoquinolino;
R4 and R5 are independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl or C1-6 alkyl substituted by 1 to 6 halogen atom(s);
R6 is hydrogen, C1-12 alkyl, C1-6 alkyl-C(═
O)(CH2)n, R11R12N(CH2)nC(═
O), C1-6 alkoxy (C1-6)alkyl, C2-8 alkenyl, C2-6 alkynyl, aryl, aryl(C1-6)alkyl, aryloxy(C1-6)alkyl, aryl (C1-6 )alkoxy (C1-6)alkyl or C1-12 alkyl substituted by up to 3 substituents selected from the groups consisting of halo, cyano, C(═
O)R10, NR11R12, R11R12NC(═
O), NR11SO2R12, C3-8 cycloalkyl, C1-6alkyl-S(O)m, aryl, heteroaryl, aryl-S(O)m, hydroxy, oxo and heterocyclic;
R7 and R8 are hydrogen;
R9 is C1-6 alkyl or C3-8 cycloalkyl;
R10 is C1-6 alkyl, aryl, OR11 or NR11R12;
L is (CR11R12)n or NR11;
M is O, NR11 or (CR11R12)n;
R11 and R12 are independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl or aryl(C1-6)alkyl;
n is an integer from 0 to 5; and
m is an integer from 0 to 2;
said heterocyclic, aryl and heteroaryl are unsubstituted or are substituted by at least one substituent selected from the group consisting of halo, C1-6 alkyl, amino, hydroxy, cyano, mono- or di-(C1-6)alkylamino, C1-6 alkoxy, aryloxy, aryl (C1-6)alkoxy, (C1-6)alkoxy carbonyl, di-(C1-6) alkylaminocarbonyl, di-(C1-6)alkylamino(C1-6)alkoxy, (C1-6)alkylsulfonylamino(C1-6)alkoxy, C1-6 alkyl substituted by 1 to 6 halogen atom(s), C1-6 alkoxy substituted by 1 to 6 halogen atom(s), phenyl, phenoxy substituted by 1 to 5 halogen atom(s) and (C1-6)alkoxy(C1-6)alkyl, with the proviso that when R9 is C1-6 alkyl, then L is not NR11; and
when R9 is C1-6 alkyl and L is (CR11R12), wherein n is 0, then M is not NR11.
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Accused Products
Abstract
This invention provides compounds of the formula (I) and (II):
or the pharmaceutically acceptable esters thereof, and the pharmaceutically acceptable salts thereof: wherein R1 is hydrogen or halo; R2 and R3 are independently hydrogen or C1-6 alkyl; R4 and R5 are independently hydrogen or C1-6 alkyl; R6 is hydrogen, C1-12 alkyl, C1-6 alkoxy (C1-6)alkyl or C1-12 alkyl substituted by up to 3 substituents selected from the groups consisting of C3-8 cycloalkyl, aryl, heteroaryl and heterocyclic; R7 and R8 are hydrogen or taken together may form alkylene chain having one or two carbon atoms; R9 is C1-6 alkyl or C3-8 cycloalkyl; R10 is C1-6 alkyl or NR11R12; L is (CR11R12)n or NR11; M is NR11 or (CR11R12)n; R11 and R12 are independently hydrogen or C1-6 alkyl; n is an integer from 0 to 5; and m is an integer from 0 to 2; said heterocyclic, aryl and heteroaryl are unsubstituted or are substituted by at least one substituent selected from the group consisting of halo and C1-6 alkyl; with the proviso that when R9 is C1-6 alkyl, L is not NR11.
These compounds have 5-HT4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound.
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Citations
11 Claims
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1. Compounds of formula (I) and (II):
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or the pharmaceutically acceptable esters thereof, and the pharmaceutically acceptable salts thereof wherein R1 is hydrogen, halo, C1-6 alkyl, aryl or heteroaryl; R2 and R3 are independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino(C1-5)alkyl or hydroxy(C1-5)alkyl;
or two of R2 and R3, or R3 and R4 taken together with the nitrogen atom to which they are attached may form a nitrogen-containing heterocycle selected from morpholino, piperazino, piperidino, pyrrolidino, azetidino, pyrazolidino, (1,2,3,4)-tetrahydroisoquinolino, or perhydroisoquinolino;R4 and R5 are independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl or C1-6 alkyl substituted by 1 to 6 halogen atom(s); R6 is hydrogen, C1-12 alkyl, C1-6 alkyl-C(═
O)(CH2)n, R11R12N(CH2)nC(═
O), C1-6 alkoxy (C1-6)alkyl, C2-8 alkenyl, C2-6 alkynyl, aryl, aryl(C1-6)alkyl, aryloxy(C1-6)alkyl, aryl (C1-6 )alkoxy (C1-6)alkyl or C1-12 alkyl substituted by up to 3 substituents selected from the groups consisting of halo, cyano, C(═
O)R10, NR11R12, R11R12NC(═
O), NR11SO2R12, C3-8 cycloalkyl, C1-6alkyl-S(O)m, aryl, heteroaryl, aryl-S(O)m, hydroxy, oxo and heterocyclic;R7 and R8 are hydrogen; R9 is C1-6 alkyl or C3-8 cycloalkyl; R10 is C1-6 alkyl, aryl, OR11 or NR11R12; L is (CR11R12)n or NR11; M is O, NR11 or (CR11R12)n; R11 and R12 are independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl or aryl(C1-6)alkyl; n is an integer from 0 to 5; and m is an integer from 0 to 2; said heterocyclic, aryl and heteroaryl are unsubstituted or are substituted by at least one substituent selected from the group consisting of halo, C1-6 alkyl, amino, hydroxy, cyano, mono- or di-(C1-6)alkylamino, C1-6 alkoxy, aryloxy, aryl (C1-6)alkoxy, (C1-6)alkoxy carbonyl, di-(C1-6) alkylaminocarbonyl, di-(C1-6)alkylamino(C1-6)alkoxy, (C1-6)alkylsulfonylamino(C1-6)alkoxy, C1-6 alkyl substituted by 1 to 6 halogen atom(s), C1-6 alkoxy substituted by 1 to 6 halogen atom(s), phenyl, phenoxy substituted by 1 to 5 halogen atom(s) and (C1-6)alkoxy(C1-6)alkyl, with the proviso that when R9 is C1-6 alkyl, then L is not NR11; and
when R9 is C1-6 alkyl and L is (CR11R12), wherein n is 0, then M is not NR11.- View Dependent Claims (2, 3, 4, 5, 6, 7, 10, 11)
R2 and R3 are independently hydrogen or C1-6 alkyl;
or two of R2 and R3, or R3 and R4 taken together with the nitrogen atoms to which they are attached may form a nitrogen-containing heterocycle selected from morpholino, piperazino, piperidino, pyrrolidino, azetidino, pyrazolidino, (1,2,3,4)-tetrahydroisoquinolino, or perhydroisoquinolino;R4 and R5 are independently hydrogen, C1-6 alkyl, aryl, C1-6 alkyl substituted with 1 to 6 halogen atom(s); said aryl is unsubstituted or is substituted by at least one substituent selected from the groups consisting of halo, C1-6 alkyl, amino, hydroxy, cyano, mono- or di-(C1-6)alkylamino, C1-6 alkoxy, aryloxy, aryl (C1-6)alkoxy, (C1-6)alkoxy carbonyl(C1-6)alkoxy, di-(C1–
6) alkylaminocarbonyl, di-(C1-6)alkylamino(C1-6)alkoxy, (C1-6)alkylsulfonylamino(C1-6)alkoxy and (C1-6)alkoxy(C1-6)alkyl;R6 is C1-12 alkyl, C3-8 alkenyl or C1-12 alkyl substituted by up to 3 substituents selected from the groups consisting of C(═
O)R10, C3-8 cycloalkyl, hydroxy, cyano, oxo, phenyl, naphthyl, phenyl-S and 5–
12 membered monocyclic or bicyclic aromatic or non-aromatic ring containing 1 to 4 heteroatoms selected from O, N and S;said phenyl, naphthyl and 5–
12 membered monocyclic or bicyclic aromatic or non-aromatic ring are unsubstituted or are substituted by at least one substituent selected from the groups consisting of halo, cyano, C1-6 alkyl, C1-6 alkyl substituted by 1 to 6 halogen atom(s), C1-6 alkoxy, C1-6 alkoxy substituted by 1 to 6 halogen atom(s), mono- or di-(C1-6)alkyl amino and C1-6 alkoxy(C1-6)alkyl; andR9 is C1-6 alkyl; R10 is C1-6alkyl, OR11 or NR11R12 wherein R11 and R12 are independently hydrogen, C3-8 cycloalkyl or C1-6 alkyl; L is (CR11R12)n or NR11, wherein R11 and R12 are independently hydrogen or C1-6 alkyl, and n is an integer from 0 to 3; and M is (CR11R12)n or NR11, wherein R11 and R12 are independently hydrogen or C1-6 alkyl, and n is an integer from 0 to 3; said heterocyclic, aryl and heteroaryl are unsubstituted or are substituted by at least one substituent selected from the group consisting of halo, C1-6 alkyl, amino, hydroxy, cyano, mono- or di-(C1-6)alkylamino, C1-6 alkoxy, aryloxy, aryl (C1-6)alkoxy, (C1-6)alkoxy carbonyl(C1-6)alkoxy, di-(C1–
6)alkylaminocarbonyl, di-(C1-6)alkylamino(C1-6)alkoxy, (C1-6)alkylsulfonylamino(C1-6)alkoxy and (C1-6)alkoxy(C1-6)alkyl.
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3. A compound according to claim 1, wherein
R1 is hydrogen, halo or heteroaryl; -
R2 and R3 are independently hydrogen or C1-6 alkyl; R4 and R5 are independently hydrogen, C1-6 alkyl or C1-6 alkyl substituted by 1 to 6 halogen atom(s); R6 is C1-10 alkyl, C3-8 alkenyl or C1-10 alkyl substituted with up to 3 substituents selected from the groups consisting of C(═
O)R10, C5-7 cycloalkyl, hydroxy, cyano, oxo, phenyl, naphthyl, phenyl-S, NR11R12 and heteroaryl selected from the groups consisting of indolyl, pyrazolyl, furyl, thienyl, oxazolyl, tetrazolyl, thiazolyl, imidazolyl, pyridyl, pyrimidinyl, pyrrolyl and quinolyl, and heterocyclic selected from the groups consisting of pyrazolino, pyrazolidino, imidazolinyl, piperidino, morpholino, thiamorpholino, pyrrolidino, piperazinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl and phthalimidolyl;said phenyl, naphthyl, heteroaryl and heterocyclic are unsubstituted or are substituted by at least one substituent selected from the groups consisting of halo, cyano, C1-6 alkyl, C1-6 alkyl substituted by 1 to 6 halogen atom(s), C1-6 alkoxy, C1-6 alkoxy substituted by 1 to 6 halogen atom(s), mono- or di-(C1-6)alkyl amino and C1-6 alkoxy(C1-6)alkyl; R10 is C1-6alkyl or C1-6 alkoxy; R11 and R12 are independently hydrogen, C3-8 cycloalkyl or C1-6 alkyl; L is (CR11R12)n or NR11, wherein R11 and R12 are independently hydrogen or methyl, and n is an integer from 0 to 2; and M is (CR11R12)n, wherein R11 and R12 are independently hydrogen or methyl, and n is an integer from 0 to 2.
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4. A compound according to claim 1, wherein
R1 is hydrogen or halo; -
R2 and R3 are hydrogen; R4 and R5 are independently hydrogen or C1-6 alkyl; R6 is C1-10 alkyl, C3-8 alkenyl or C1-10 alkyl substituted with up to 3 substituents selected from the groups consisting of C(═
O)R10, C5-7 cycloalkyl, oxo, phenyl, naphthyl, phenyl-S, NR11R12, heteroaryl selected from the groups consisting of indolyl, furyl, thienyl, oxazolyl, pyridyl, pyrrolyl and quinolyl, and heterocyclic selected from the groups consisting of piperidino, morpholino, pyrrolidino, piperazinyl, phthalimidolyl, pyrrolidinyl and tetrahydropyaranyl;said phenyl, naphthyl, heteroaryl and heterocyclic are unsubstituted or are substituted by at least one substituent selected from the groups consisting of halo, cyano, C1-6 alkyl, C1-6 alkyl substituted by 1 to 6 halogen atom(s), C1-6 alkoxy, C1-6 alkoxy substituted by 1 to 6 halogen atom(s), mono- or di-(C1-6)alkyl amino and C1-6 alkoxy(C1-6)alkyl; R10 is C1-6 alkoxy; R11 and R12 are independently C3-8 cycloalkyl or C1-6 alkyl; L is (CR11R12)n or NR11, wherein R11 and R12 are independently hydrogen or methyl, and n is an integer from 0 to 2; and M is (CR11R12)n, wherein R11 and R12 are independently hydrogen or methyl, and n is an integer from 0 to 2.
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5. A compound according to claim 1, wherein
R1 is hydrogen or halo; -
R2and R3 are hydrogen; R4 and R5 are hydrogen; R6 is C1-10 alkyl, C3-8 alkenyl or C1-10 alkyl substituted with up to 3 substituents selected from the groups consisting of C1-6 alkoxycarbonyl, C5-7 cycloalkyl, oxo, phenyl, naphthyl, phenyl-S, heteroaryl selected from the groups consisting of indolyl and pyridyl, and heterocyclic selected from the groups consisting of pyrrolyl, piperidino, phthalimidolyl and tetrahydropyranyl; said phenyl, naphthyl, heteroaryl and heterocyclic are unsubstituted or are substituted by at least one substituent selected from the groups consisting of halo, C1-6 alkyl, C1-6 alkyl substituted by 1 to 6 halogen atom(s), C1-6 alkoxy and C1-6 alkoxy substituted by 1 to 6 halogen atom(s); R10 is C1-6alkoxy; L is (CR11R12)n or NR11, wherein R11 and R12 are independently hydrogen or methyl, and n is an integer from 0 to 2; and M is (CR11R12)n, wherein R11 and R12 are independently hydrogen or methyl, and n is an integer from 0 to 2.
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6. A compound according to claim 1, wherein
R1 is hydrogen or halo; -
R2 and R3 are hydrogen; R4 and R5 are hydrogen; R6 is isobutyl, cyclohexylmethyl, n-butyl, indolylethyl, phenylethyl, fluorophenylethyl, ethoxycarbonyl(n-propyl)methyl, methoxycarbonyl(phenyl)methyl, naphthylethyl, trifuluoromethoxyphenylmethyl, n-heptyl, n-butyl(ethoxycarbonyl)methyl, (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl, isopentyl, n-hexyl, hexenyl, chlorophenylmethyl, dichlorophenylmethyl, pyrrolylethyl, ethoxycarbonyl(ethyl)methyl, cyclohexylethyl, ethoxycarbonyl(isopropyl)methyl, ethylhexyl, phenylthioethyl, methylpentyl, (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl, bromofluorophenylmethyl, butylmethyl, bromophenylmethyl, dimethoxyphenyl-oxoethyl, benzoylethyl, 3,3-dimethyl-2-oxobutyl, 1,3,3-trimethyl-2-oxobutyl-2-oxobutyl, 2-hydroxy-3,3-dimethylbutyl, 4-methoxycarbonyl-3,3-dimethyl-2-oxo-butyl, 3,3-dimethyl-2-oxobutyl, neopentyl, [(dimethylamino)carbonyl]pentyl, (piperidinylcarbonyl)pentyl or {[cyclohexyl(methyl)amino]carbonyl}pentyl; R10 is C1-6alkoxy; L is (CR11R12)n or NR11, wherein R11 and R12 are independently hydrogen or methyl, and n is an integer from 0 to 2; and M is chemical bond or methylene.
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7. A compound according to claim 1, wherein
R1 is hydrogen or halo; -
R2 and R3 are hydrogen; R4 and R5 are hydrogen; R6 is isobutyl, cyclohexylmethyl, n-butyl, indolylethyl, phenylethyl, fluorophenylethyl, ethoxycarbonyl(n-propyl)methyl, methoxycarbonyl(phenyl)methyl, naphthylethyl, 4-methoxycarbonyl-3,3-dimethyl-2-oxo-butyl, 3,3-dimethyl-2-oxobutyl, neopentyl, [(dimethylamino)carbonyl]pentyl, (piperidinylcarbonyl)pentyl or {[cyclohexyl(methyl)amino]carbonyl}pentyl; R10 is C1-6alkoxy; L is NR11; and M is chemical bond or methylene.
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10. A pharmaceutical composition comprising a compound according to any one of claims 1 to 9 and a pharmaceutically acceptable carrier.
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11. A method of treating gastroesophageal reflux disease comprising administering a therapeutically effective amount of a compound according to any one of claims 1 to 9 to a mammal in need thereof.
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8. A compound selected from
6-amino-5-chloro-2-oxo-N-({1-[4-(trifluoromethoxy)benzyl]-4-piperidinyl}methyl)-1,2-dihydro-3-pyridinecarboxamide; -
6-amino-5-chloro-N-[(1-heptyl-4-piperidinyl)methyl]-2-oxo-1,2-dihydro-3-pyridinecarboxamide; ethyl 2-[4-({[(6-amino-5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)carbonyl]-amino}methyl)-1-piperidinyl]hexanoate; 6-amino-5-chloro-N-({1-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-{[1-(3-methylbutyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-[(1-hexyl-4-piperidinyl)methyl]-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-{[1-(5-hexenyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-{[1-(3-chlorobenzyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-{[1-(2,6-dichlorobenzyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-2-oxo-N-({1-[2-(1H-pyrrol-1-yl)ethyl]-4-piperidinyl}methyl)-1,2-dihydro-3-pyridinecarboxamide; ethyl 2-[4-({[(6-amino-5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)carbonyl]-amino}methyl)-1-piperidinyl]butanoate; 6-amino-5-chloro-N-{[1-(2-cyclohexylethyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; ethyl 2-[4-({[(6-amino-5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)carbonyl]-amino}methyl)-1-piperidinyl]-3-methylbutanoate; 6-amino-5-chloro-N-{[1-(2-ethylhexyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-2-oxo-N-({1-[2-(phenylthio)ethyl]-4-piperidinyl}methyl)-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-{[1-(4-methylpentyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-N-{[1-(4-bromo-2-fluorobenzyl)-4-piperidinyl]methyl}-5-chloro-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-N-[(1-butyl-4-piperidinyl)methyl]-5-chloro-2-oxo-1,2-dihydro-3-pyridinecarboxamide di-hydrochloride; 6-amino-5-chloro-N-{[1-(2-methylbutyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-N-{[1-(2-bromobenzyl)-4-piperidinyl]methyl}-5-chloro-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-N-{[1-(3-bromobenzyl)-4-piperidinyl]methyl}-5-chloro-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 1-(6-amino-5-chloro-2-methoxy-3-pyridinyl)-3-(1-isobutyl-4-piperidinyl)-1-propanone; 6-amino-5-chloro-N-{[1-(cyclohexylmethyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(1H-indol-2-yl)ethyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-2-oxo-N-{[1-(2-phenylethyl)-4-piperidinyl]methyl}-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(4-fluorophenyl)ethyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(1H-indol-3-yl)ethyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; ethyl 2-[4-({[(6-amino-5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)carbonyl]-amino}methyl)-1-piperidinyl]pentanoate; methyl [4-({[(6-amino-5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)carbonyl]-amino}methyl)-1-piperidinyl](phenyl)acetate; 6-amino-5-chloro-N-{[1-(2-methylpropyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(1-naphthyl)ethyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(2,4-dimethoxyphenyl)-2-oxoethyl]piperidin-4-yl}methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-Amino-5-chloro-N-{[1-(1-methyl-2-oxo-2-phenylethyl)piperidin-4-yl]methyl}-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-amino-5-chloro-3-{3-[1-(3,3-dimethyl-2-oxobutyl)piperidine-4-yl]propanoyl}pyridin-2(1H)-one; 6-amino-5-chloro-3-{3-[1-(1,3,3-trimethyl-2-oxobutyl-2-oxobutyl)piperidine-4-yl]propanoyl}pyridin-2(1H)-one; 6-amino-5-chloro-3-{3-[1-(cyclohexylmethyl)piperidine-4-yl]propanoyl}pyridin-2(1H)-one; 6-amino-5-chloro-3-{3-[1-(2-hydroxy-3,3-dimethylbutyl)piperidine-4-yl]propanoyl}pyridin-2(1H)-one; methyl 5-[4-({[(6-amino-5-chloro-2-oxo-1,2-dihydropyridin-3-yl)carbonyl]-amino}methyl)piperidin-1-yl]-3,3-dimethyl-4-oxopentanoate; 6-amino-5-chloro-N-{[1-(3,3-dimethyl-2-oxobutyl)piperidin-4-yl]methyl}-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-amino-5-chloro-N-[(1-neopentylpiperidin-4-yl)methyl]-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-amino-5-chloro-N-[(1-{1-[(methylamino)carbonyl]pentyl}piperidin-4-yl)methyl]-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-amino-5-chloro-2-oxo-N-({1-[1-(piperidin-1-ylcarbonyl)pentyl]piperidin-4-yl}methyl)-1,2-dihydropyridine-3-carboxaimde;
or6-amino-5-chloro-N-{[1-(1-{[cyclohexyl(methyl)amino]carbonyl}pentyl)-piperidine-4-yl]methyl}-2-oxo-1,2-dihydropyridine-3-carboxamide; and
salts thereof.
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9. A compound selected from
1-(6-amino-5-chloro-2-methoxy-3-pyridinyl)-3-(1-isobutyl-4-piperidinyl)-1-propanone; -
6-amino-5-chloro-N-{[1-(cyclohexylmethyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(1H-indol-2-yl)ethyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-2-oxo-N-{[1(2-phenylethyl)-4-piperidinyl]methyl}-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(4-fluorophenyl)ethyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(1H-indol-3-yl)ethyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; ethyl 2-[4-({[(6-amino-5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)carbonyl]-amino}methyl)-1-piperidinyl]pentanoate; methyl [4-({[(6-amino-5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)carbonyl]-amino}methyl)-1-piperidinyl](phenyl)acetate; 6-amino-5-chloro-N-{[1-(2-methylpropyl)-4-piperidinyl]methyl}-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-N-({1-[2-(1-naphthyl)ethyl]-4-piperidinyl}methyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; 6-amino-5-chloro-2-oxo-N-({1-[4-(trifluoromethoxy)benzyl]-4-piperidinyl}methyl)-1,2-dihydro-3-pyridinecarboxamide; methyl 5-[4-({[(6-amino-5-chloro-2-oxo-1,2-dihydropyridin-3-yl)carbonyl]-amino}methyl)piperidin-1-yl]-3,3-dimethyl-4-oxopentanoate; 6-amino-5-chloro-N-{[1-(3,3-dimethyl-2-oxobutyl-2-oxobutyl)piperidin-4-yl]methyl}-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-amino-5-chloro-N-[(1-neopentylpiperidin-4-yl)methyl]-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-amino-5-chloro-N-[(1-{1-[(methylamino)carbonyl]pentyl}piperidin-4-yl)methyl]-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-amino-5-chloro-2-oxo-N-({1-[1-(piperidin-1-ylcarbonyl)pentyl]piperidin-4-yl}methyl)-1,2-dihydropyridine-3-carboxaimde;
or6-amino-5-chloro-N-{[1-(1-{[cyclohexyl(methyl)amino]carbonyl}pentyl)-piperidine-4-yl]methyl}-2-oxo-1,2-dihydropyridine-3-carboxamide; and
salts thereof.
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Specification