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US 6,608,057 B2Granted
Compounds useful as reversible inhibitors of cathepsin S
AssigneeBoehringer Ingelheim Pharmaceuticals, Inc.
InventorsCharles L. Cywin, Michel J. Emmanuel, Tina Morwick, Denice M. Spero, David S. Thomson, Yancey D. Ward
Life of this patent
Estimating the term…
Abstract
Disclosed are cathepsin S reversible inhibitory compounds of the formulas (I),(Ia) and (II),(IIa) as defined herein. The compounds are useful for treating autoimmune diseases. Also disclosed are processes for making such novel compounds
Claims28
A compound of formula (I):
- wherein:
- A is —C(Y)— or —SO2—
- Y is O, S or NRa wherein Ra is selected from the group consisting of H, alkyl, aryl, alkoxy, aryloxy, alkylamino and arylamino;
- R1 morpholinyl wherein R1 is unsubstituted or substituted by one or more Rb;
- Rb is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, Rb is unsubstituted or substituted by one or more Rc;
- Rd is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl, aroyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;
- R2 is H or alkyl;
- R3 is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R3 is unsubstituted or substituted by one or more groups of the formula Rd;
- Rd is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, Rd is unsubstituted or substituted by one or more Re;
- Re is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl, aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;
- R4 is H or alkyl;
- R5 is H, alkyl or cycloalkyl;
- R6 is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R6 is unsubstituted or substituted by one or more groups of the formula Rf;
- Rf is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkanoyl, aroyl, arylalkoxy, heteroarylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylalkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, Rf is unsubstituted or substituted by one or more Rg;
- Rg is selected from the group consisting of alkyl, cycloalkyl, aryl unsubstituted or substituted by halogen, C1-5alkyl or C1-5alkoxy, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;
- or R5 together with R6 form a 3 to 6 membered carbocyclic ring, the carbocyclic ring being unsubstituted or substituted with one or more Rh;
- Rh is selected from the group consisting of alkyl, aryl, alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, carbamoyl wherein the nitrogen atom is unsubstituted or mono or di-substituted by alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl or heteroaryl;
- halogen, hydroxy, carboxy and cyano;
- R7 is R8—C(Z)—;
- wherein Z is O, S, or NR1 wherein R1 is selected from the group consisting of H, alkyl, aryl, alkoxy, aryloxy and hydroxy;
- R8 is a heteroaryl ring selected from the group consisting of furanyl, thienyl, pyridazinyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl indolyl, isoindolyl, benzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, triazolyl, tetrazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl and phenazinyl wherein any of the above R8 can be unsubstituted or substituted by one or more Rj;
- Rj is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, arylalkyl, alkoxy, aryloxy, alkanoyl, aroyl, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylalkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, Rj is unsubstituted or substituted by one or more Rk;
- Rk is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino, arylalkoxycarbonylamino, arylalkoxycarbonylaminoalkyl, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;
- and
- X is O, S or N—OH;
- or
- the pharmaceutically acceptable salts, esters, tautomers, individual isomers and mixtures of isomers thereof;
- with the proviso that when R6 is alkyl the alkyl must be substituted with Rf wherein Rf is not hydroxy, sulfhydryl or halogen.
30 more elements
A compound of formula (Ia):
- wherein:
- A is —C(Y)— or —SO2—
- Y is O, S or NRa wherein Ra is selected from the group consisting of H, alkyl, aryl, alkoxy, aryloxy, alkylamino and arylamino;
- R1 is morpholinyl wherein R1 is unsubstituted or substituted by one or more Rb;
- Rb is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, Rb is unsubstituted or substituted by one or more Rc;
- Rc is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl, aroyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;
- R2 is H or alkyl;
- R3 is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R3 is unsubstituted or substituted by one or more groups of the formula Rd;
- Rd is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyl, aroyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, Rd is unsubstituted or substituted by one or more Re;
- Re is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, alkanoyl, aroyl, amino, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;
- R4 is H or alkyl;
- R5 is H, alkyl or cycloalkyl;
- R6 is H, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R6 is unsubstituted or substituted by one or more groups of the formula Rf;
- Rf is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, alkanoyl, aroyl, arylalkoxy, heteroarylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylalkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, Rf is unsubstituted or substituted by one or more Rg;
- Rg is selected from the group consisting of alkyl, cycloalkyl, aryl unsubstituted or substituted by halogen, C1-5alkyl or C1-5alkoxy, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino;
- or R5 together with R6 form a 3 to 6 membered carbocyclic ring, the carbocyclic ring being unsubstituted or substituted with one or more Rh;
- Rh is selected from the group consisting of alkyl, aryl, alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, carbamoyl wherein the nitrogen atom is unsubstituted or mono or di-substituted by alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl or heteroaryl;
- halogen, hydroxy, carboxy and cyano;
- R7 is R8—C(Z)—;
- wherein Z is O, S, or NRi wherein Ri is selected from the group consisting of H, alkyl, aryl, alkoxy, aryloxy and hydroxy;
- R8 is a heteroaryl ring selected from the group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, nyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indolyl, isoindolyl, benzofuranyl, benzothienyl, indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, triazolyl, tetrazolyl, purinyl, quinolizinyl, quinolinyl, isociuinolinyl, cinnolinyl, phthalazinyl, ciuinazolinyl, ciuinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, aeridinyl and phenazinyl unsubstituted or substituted by one or more Rj;
- Rj is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, arylalkyl, alkoxy, aryloxy, alkanoyl, aroyl, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylalkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- alkoxycarbonylamino, aryloxycarbonylamino, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl;
- halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, Rj is unsubstituted or substituted by one or more Rk;
- Rk is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkoxy, aryloxy, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, alkanoyloxy, aroyloxy, carbamoyl wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkanoylamino, aroylamino, alkylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, arylthio wherein the sulfur atom is unoxidized or oxidized to a sulfoxide or sulfone, ureido wherein either nitrogen atom is unsubstituted or independently substituted by alkyl, aryl, heterocyclyl or heteroaryl, alkoxycarbonylamino, aryloxycarbonylamino, arylalkoxycarbonylamino, arylalkoxycarbonylaminoalkyl, alkylcarbamoyloxy, arylcarbamoyloxy, alkylsulfonylamino, arylsulfonylamino, alkylaminosulfonyl, arylaminosulfonyl, amino wherein the nitrogen atom is unsubstituted or independently mono or di-substituted by alkyl, aryl, heterocyclyl or heteroaryl, halogen, hydroxy, oxo, carboxy, cyano, nitro, amidino and guanidino, wherein Rk is unsubstituted or substituted by Rl;
- Rl is selected from the group consisting of alkyl, cycloalkyl, aryl, and benzyl;
- and
- X is O, S or N—OH;
- or the pharmaceutically acceptable salts, esters, tautomers, individual isomers and mixtures of isomers thereof;
- with the following provisos:
- when R6 is alkyl the alkyl must be substituted with Rf wherein Rf is not hydroxy, sulfhydryl or halogen;
- and
- when R1 is C1alkyl then Rb cannot be carbamoyl, alkanoylamino, aroylamino, ureido, alkoxycarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, amino, amidino or guanidino wherein each said Rb is linked to said R1 via the nitrogen atom thereof.
33 more elements
A compound selected from the group consisting of:
- N-(4-Morpholinecarbonyl)-L-leucine-[1S(benzthiazol-2-ylcarbonyl)-3-phenylpropyl]amide;
- N-(4-Morpholinecarbonyl)-L-leucine-[1R,S(benzoxazol-2-ylcarbonyl)-3-phenYlpropyl]amide
- N-(4-morpholinecarbonyl)-L-leucine[[1[(6-phenylcarbamoyl)benzothiazol-2-ylcarbonyl)-3-phenyipropyl]]amide;
- N-(4-Morpholinecarbonyl]-L-leucine 1RS-((5-phenyloxazol-2-yl)carbonyl)-3-phenylpropylamide;
- N-(4-Morpholinecarbonyl]-L-leucine 1S-(oxazol-2-ylcarbonyl)-3-phenylpropylamide;
- N-(4-morpholinecarbonyl)-L-(4-methyl)leucine[1-(Benzothiazol-2-ylcarbonyl)-3-phenylpropyl]amide;
- and
- the pharmaceutically acceptable salts, esters, tautomers, individual isomers and mixtures of isomers thereof.
5 more elements
A compound selected from the group consisting of:
- Morpholine-4-carboxylic acid{1-(S)-[1(S)-(2,4-diphenyl-oxazole-5-carbonyl]3-phenyl-propylcarbamoyl]-3,3-dimethylbutyl} amide;
- Morpholine-4-carboxylic acid{2-cyclohexyl-1-(S)-[1-(S)-(2,4-diphenyl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoylfethyl}amide;
- Morpholine-4-carboxylic acid{1-(S)-[2,4-diphenyl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3-methylbutyl}amide;
- Morpholine-4-carboxylic acid {2-cyclohexyl-1-(S)-[2-(2,4-diphenyl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-ethyl}-amide;
- Morpholine-4-carboxylic acid {1-(S)-[2-(2,4-diphenyl-oxazol-5-yl)-2-oxo-ethylcarbamoyl]-3,3-dimethylbutyl}-amide;
- Morpholine-4-carboxylic acid (1-(S)-{1-(S)-[2-(3-benzyloxy-phenyl)-oxazole-5-carbonyl]-3-phenyl-propylcarbamoyl}-3-methyl-butyl)-amide
- Morpholine-4-carboxylic acid {2-cyclohexyl-1-(S)-[1(R,S)-(4-isobutyl-2-pyrinin-2-yl-oxazole-5-carbonyl)-3-phenyl-propylcarbamoylfethyl}amide
- and the pharmaceutically acceptable salts, esters, tautomers, individual isomers and mixtures of isomers thereof.
5 more elements
Dependencies are inferred from the claim text.