US 2003/0199692 A1Published application

Propanoic acid derivatives that inhibit the binding of integrins to their receptors

AssigneeTexas Biotechnology Corporation

InventorsRonald J. Biediger, Brian Dupre, Linda K. Hamaker, George W. Holland, Jamal M. Kassir, Wen Li, Robert V. Market, Noel Nguyen, Ian L. Scott, Chengde Wu, E. Radford Decker

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Abstract

A method for the inhibition of the binding of α4β1 integrin to its receptors, for example VCAM-1 (vascular cell adhesion molecule-1) and fibronectin; compounds that inhibit this binding; pharmaceutically active compositions comprising such compounds; and the use of such compounds either as above, or in formulations for the control or prevention of diseases states in which α4β1 is involved.

Claims20

Dependent claims

A compound of the structure

37
wherein circle Q represents one or more rings;
q is an integer of zero to six;
M is selected from the group consisting of —C(R9)(R10)— and —(CH2)u—, wherein u is an integer of from 0 to 3;
J is selected from the group consisting of —O—, —S— and —NR12—;
T is selected from the group consisting of —C(O)— and —(CH2)b— wherein b is an integer of from 0 to 3;
L is selected from the group consisting of —O—, —NR13—, —S—, and —(CH2)v— wherein v is an integer of 0 or 1;
X is selected from the group consisting of —CO2B, —PO3H2, —SO3H, —SO2NH2, —SO2NHCOR14, —OPO3H2, —C(O)NHC(O)R15, —C(O)NHSO2R16, tetrazolyl, oxazolyl and hydroxyl;
R11, R12 and R13 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, —CH═NOH, haloalkyl, alkoxyalkyl, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
and,
B, R1, R4, R6, R8, R9, R10, R14, R15 and R16 at each occurrence are independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, —CF3, —CO2H, —SH, —CN, —NO2, —NH2, —OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, —N(C1-C3 alkyl)—C(O)(C1-C3 alkyl), —NHC(O)N(C1-C3 alkyl)C(O)—NH(C1-C3 alkyl), —NHC(O)NH(C1-C6 alkyl), —NHSO2(C1-C3 alkyl), —NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, —C(O)O—(C1-C3)alkyl, —C(O)NH—(C1-C3)alkyl, —C(O)N(C1-C3 alkyl)2, —CH═NOH, —PO3H2, —OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, —SO2—(C1-C3 alkyl), —SO3—(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
wherein B, R, R4, R6, R8, R9, R10, R11, R12, R13, R14, R15 and R16 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
wherein when L is —NR3—, R4 and R13 taken together may form a ring;
and wherein R6 and R8 taken together may form a ring;
and wherein when M is —C(R9)(R10)—, R9 and R10 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.

13 more elements

A compound of the structure

38
wherein Y, at each occurrence, is independently selected from the group consisting of C(O), N, CR7, C(R2)(R3), NR5, CH, O and S;
m is an integer of from 2 to 5;
W is selected from the group consisting of C, N and CR22;
T is selected from the group consisting of C(O) and (CH2)b wherein b is an integer of 0 to 3;
L is selected from the group consisting of O, NR13, S, and (CH2)n wherein n is an integer of 0 or 1;
R5, R11 and R13 at each occurrence, are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, —CH═NOH, haloalkyl, alkoxyalkyl, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
and,
B, R2, R3, R4, R6, R7, R8, R9, R10 and R22 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, —CF3, —CO2H, —SH, —CN, —NO2, —NH2, —OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, —N(C1-C3 alkyl)—C(O)(C1-C3 alkyl), —NHC(O)N(C1-C3 alkyl)C(O)—NH(C1-C3 alkyl), —NHC(O)NH(C1-C6 alkyl), —NHSO2(C1-C3 alkyl), —NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, —C(O)O—(C1-C3)alkyl, —C(O)NH—(C1-C3)alkyl, —C(O)N(C1-C3 alkyl)2, —CH═NOH, —PO3H2, —OPO3H2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, —SO2—(C1-C3 alkyl), —SO3—(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
wherein B, R2, R3, R4, R6, R7, R8, R9, R10, R11, R13 and R22 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
and wherein when L is —NR13—, R4 and R13 taken together may form a ring;
and wherein R6 and R8 taken together may form a ring;
and wherein R9 and R10 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.

11 more elements

A compound of the structure

39
wherein q is an integer of zero to four;
T is selected from the group consisting of C(O) and (CH2)b wherein b is an integer of 0 to 3;
L is selected from the group consisting of O, NR13, S, and (CH2)n wherein n is an integer of 0 or 1;
R11 and R13 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, —CH═NOH, haloalkyl, alkoxyalkyl, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
and,
B, R1, R4, R6, R8, R9 and R10 at each occurrence are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkoxy, aliphatic acyl, —CF3,—CO2H, —SH, —CN, —NO2, —NH2, —OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, —N(C1-C3 alkyl)—C(O)(C1-C3 alkyl), —NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3 alkyl), —NHC(O)NH(C1-C6 alkyl), —NHSO2(C1-C3 alkyl), —NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, —C(O)O—(C1-C3)alkyl, —C(O)NH(C1-C3)alkyl, —C(O)N(C1-C3 alkyl)2, —CH═NOH, —PO3H2, —OPO3H2, haloalkyl, alkoxyalkoxy, carboxyaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, —SO2—(C1-C3 alkyl), —SO3—(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
wherein B, R1, R4, R6, R8, R9, R10, R11 and R13 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
and wherein when L is —NR13—, R4 and R13 taken together may form a ring;
and wherein R6 and R8 taken together may form a ring;
and wherein R9 and R10 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.

9 more elements

A compound of the structure

40
wherein s is an integer of zero to five;
R21 is selected from the group consisting of aryl, alkyheterocyclyl, heterocyclylalkyl, heterocycloyl, aralkyl, alkylaryl, alkyl, aroyl, aryloxy, cycloalkyl, cycloalkenyl, cycloalkynyl, biaryl, arylamino, thioaryl and diarylamino;
B, R6, R8, R9, R10, R17, R18, R19 and R20 at each occurrence are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkoxy, aliphatic acyl, —CF3, —CO2H, —SH, —CN, NO2, —NH2, —OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, —N(C1-C3 alkyl)—C(O)(C1-C3 alkyl), —NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3 alkyl), —NHC(O)NH(C1-C6 alkyl), —NHSO2(C1-C3 alkyl), —NHSO2(aryl), alkoxyalkyl, alkylamino, alkenylamino, di(C1-C3)amino, —C(O)O—(C1-C3)alkyl, —C(O)NH(C1-C3)alkyl, —C(O)N(C1-C3 alkyl)2, —CH═NOH, —PO3H2, —OPO3H2, haloalkyl, alkoxyalkoxy, carboxyaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, —SO2—(C1-C3 alkyl), —SO3—(C1-C3 alkyl), sulfonamido, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
R11 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, —CH═NOH, haloalkyl, alkoxyalkyl, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
and,
wherein B, R6, R8, R9, R10, R11, R17, R18, R19, R20 and R21 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
and wherein R6 and R8 taken together may form a ring;
and wherein R9 and R10 taken together may form a ring;
and wherein R18 and R19 taken together may form a ring;
and wherein R19 and R20 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.

9 more elements

A compound of the structure

41
wherein circle Q is a ring selected from the group consisting of
42
q is an integer of zero to four;
B, R1, R6, R8, R9 and R10 are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, alkynoxy, thioalkoxy, hydroxyalkyl, aliphatic acyl, —CF3, —CO2H, —SH, —CN, NO2, —NH2, —OH, alkynylamino, alkoxycarbonyl, heterocycloyl, carboxy, —N(C1-C3 alkyl)—C(O)(C1-C3 alkyl), —NHC(O)NH(C1-C3 alkyl), —NHC(O)N(C1-C3 alkyl)C(O)NH(C1-C3 alkyl), —NHSO2(C1-C3 alkyl), —NHSO2(aryl), alkoxyalkyl,-C1-C3 alkylamino, alkenylamino, alkynylamino, di(C1-C3 alkyl)amino, —C(O)O—(C1-C3 alkyl), —C(O)NH—(C1-C3 alkyl), —CH═NOH, —PO3H2, —OPO3H2, —C(O)N(C1-C3 alkyl)2, haloalkyl, alkoxyalkoxy, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, sulfonyl, —SO2—(C1-C3 alkyl), —SO3—(C1-C3 alkyl), sulfonamido, aryloxyalkyl, carboxyl, carbamate and —C(O)NH(benzyl);
R5 and R11 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aliphatic acyl, alkynylamino, alkoxycarbonyl, heterocycloyl, —CH═NOH, haloalkyl, alkoxyalkyl, carboxaldehyde, carboxamide, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, aryl, aroyl, aryloxy, arylamino, biaryl, thioaryl, diarylamino, heterocyclyl, alkylaryl, aralkenyl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, carbamate, aryloxyalkyl and —C(O)NH(benzyl) groups;
and,
R21 is selected from the group consisting of aryl, alkyheterocyclyl, heterocyclylalkyl, heterocycloyl, aralkyl, alkylaryl, alkyl, aroyl, aryloxy, cycloalkyl, cycloalkenyl, cycloalkynyl, biaryl, arylamino, thioaryl and diarylamino;
wherein B, R1, R5, R6, R8, R9, R10, R11 and R21 are unsubstituted or substituted with at least one electron donating or electron withdrawing group;
and wherein R6 and R8 taken together may form a ring;
and wherein R9 and R10 taken together may form a ring;
or a pharmaceutically acceptable salt thereof.

9 more elements

A compound selected from the group consisting of (3S)-(1,3-benzodioxol-5-yl)-3-(((2S)-2-(2-oxo-3-(2-thienylmethyl)tetrahydro-1(2H)-pyrimidinyl)hexanoyl)amino) propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-((2R,S)-2-(3-benzyl-5-methyl-2-oxo-1(2H)-pyridinyl)hexanoylamino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-((2R,S)-2-(3-(3-chlorobenzyl)-5-methyl-2-oxo-1(2H)-pyridinyl)hexanoylamino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-(((2S)-2-(2-oxo-3-(phenylmethyl)-1(2H)-pyridinyl)hexanoyl)amino) propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-((2-(3-chlorophenyl)methyl)-5-methyl-2-oxo-1(2H)-pyridinyl)hexanoyl)amino)propanoic acid, (3S)-3-{[(2S)-2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(3,5-dimethoxyphenyl)propanoic acid, (3S)-3-{[(2S)-2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(3-fluoro-4-methoxyphenyl)propanoic acid, (3S)-3-{[2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-({2-[3-(3-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-(3-isopropoxyphenyl)-3-({2-[3-(2-methoxybenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-{[2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(3-ethoxy-4-methoxyphenyl)propanoic acid, (3S)-3-{[2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(4-methoxy-3-methylphenyl)propanoic acid, (3S)-3-{[2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-phenylpropanoic acid, (3S)-3-({2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-({2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(3-isopropoxyphenyl)propanoic acid, (3S)-3-({2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-phenylpropanoic acid, (3S)-3-(1-methyl-1H-indol-6-yl)-3-({2-[5-methyl-2-oxo-3-(phenylmethyl)-1(2H)-pyridinyl]hexanoyl}amino)propanoic acid, (3S)-3-{3-[(1-methylethyl)oxy]phenyl}-3-({2-[5-methyl-3-(2-naphthalenylmethyl)-2-oxo-1(2H)-pyridinyl]hexanoyl}amino)propanoic acid, (3S)-3-({2-[5-methyl-2-oxo-3-(phenylmethyl)-1(2H)-pyridinyl]hexanoyl}amino)-3-[3-(2-methylpropyl)phenyl]propanoic acid, (3S)-3-[3-(difluoromethyl)phenyl]-3-({2-[5-methyl-2-oxo-3-(phenylmethyl)-1(2H)-pyridinyl]hexanoyl}amino)propanoic acid, (3S)-3-{3-[(1-methylethyl)oxy]phenyl}-3-({2-[5-methyl-3-[(2-methylphenyl)methyl]-2-oxo-1(2H)-pyridinyl]hexanoyl}amino)propanoic acid, (3S)-3-(3-fluorophenyl)-3-({2-[5-methyl-2-oxo-3-(phenylmethyl)-1(2H)-pyridinyl]hexanoyl}amino)propanoic acid, (3S)-3-({2-[3-[(2-chloro-4-fluorophenyl)methyl]-5-methyl-2-oxo-1(2H)-pyridinyl]hexanoyl}amino)-3-{3-[(1-methylethyl)oxy]phenyl}propanoic acid and (3S)-3-{3-[(1-methylethyl)oxy]phenyl}-3-({2-[5-methyl-2-oxo-1-(phenylmethyl)-1,2-dihydro-3-pyridinyl]-2-phenylacetyl}amino) propanoic acid and pharmaceutically acceptable salts thereof.

A compound selected from the group consisting of (3S)-3-{[(2S)-2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(3′,4′-dimethoxy-1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(3′,4′-dimethoxy-1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-(1,1′-biphenyl-4-yl)-3-({(2S)-2-[3-(2-chloro-6-methylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-{[(2S)-2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-(1,1′-biphenyl-4-yl)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-{[(2S)-2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(4′-methyl-1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4′-methyl-1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chloro-6-methylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4′-methyl-1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-{[(2S)-2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(2′,6′-dimethoxy-1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(2′,6′-dimethoxy-1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chloro-6-methylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(2′,6′-dimethoxy-1,1′-biphenyl-4-yl)propanoic acid, (3S)-3-{[(2S)-2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(1,1′-biphenyl-3-yl)propanoic acid, (3S)-3-(1,1′-biphenyl-3-yl)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-(1,1′-biphenyl-3-yl)-3-({(2S)-2-[3-(2-chloro-6-methylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-{[(2S)-2-(3-benzyl-5-methyl-2-oxopyridin-1(2H)-yl)hexanoyl]amino}-3-(2′-methoxy-1,1′-biphenyl-3-yl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(2′-methoxy-1,1′-biphenyl-3-yl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chloro-6-methylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(2′-methoxy-1,1′-biphenyl-3-yl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-fluoro-6-methoxybenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-({(2S)-2-[3-(2,6-dimethylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-({(2S)-2-[3-(3,5-dimethylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-({(2S)-2-[3-(2,6-dichlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chloro-6-fluorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-({(2S)-2-[3-(2,6-difluorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(2,6-difluorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(2-chloro-6-fluorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(2,6-dichlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(2,6-dimethylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(3,5-dimethylbenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(2-fluoro-6-methoxybenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(3,4-diethoxyphenyl)propanoic acid, (3S)-3-(3,4-diethoxyphenyl)-3-({(2S)-2-[3-(2,6-difluorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)propanoic acid, (3S)-3-({(2S)-2-[3-(2,6-difluorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chloro-6-fluorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]hexanoyl}amino)-3-(3-ethoxyphenyl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]-3-methylbutanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]-4-methylpentanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]-4-methylpentanoyl}amino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]-3-methylbutanoyl}amino)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]-3-phenylpropanoyl}amino)propanoic acid, (3S)-3-({(2S)-2-[3-(2-chlorobenzyl)-5-methyl-2-oxopyridin-1(2H)-yl]-3-phenylpropanoyl}amino)-3-(4-methylphenyl)propanoic acid, (3S)-3-(1,3-benzodioxol-5-yl)-3-(((2R)-2-(1-benzyl-5-methyl-2-oxo-1,2-dihydropyridin-3-yl)hexanoyl)amino) propanoic acid and pharmaceutically acceptable salts thereof.

Dependencies are inferred from the claim text.

Facts

Application: 09/973,414Filed 9 Oct 2001
Priority: 7 May 1999
Published: 23 Oct 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 213/64
One oxygen atom: attached in position 2 or 6
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
A61P 35/00
Antineoplastic agents
C07D 317/60
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring: radicals…

Family

Application60/132,967Us provisional application · filed 7 May 1999
Application60/170,441Us provisional application · filed 10 Dec 1999
Application09/565,507Continuation in part · filed 5 May 2000
Application09/706,996Continuation in part · filed 6 Nov 2000
Application09/973,414Continuation in part · filed 9 Oct 2001
US 6,723,711 B2Related patent
US 2003/0199692 A1This patent

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