US 2010/0249405 A1Published application

Organic Compounds

AssigneeNovartis AG

InventorsZhuoliang Chen, Run-Ming David Wang, Ming Chen, Christopher Sean Straub, Leigh Zawel

Life of this patent

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Abstract

The present invention relates to novel IAP inhibitor compounds of formula I:

Claims10

Dependent claims

A compound of formula I:

and pharmaceutically acceptable salts thereof, wherein
R1 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl or C3-C10 cycloalkyl, which R1 may be unsubstituted or substituted;
R2 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, or C3-C10 cycloalkyl, which R2 may be unsubstituted or substituted;
R1 and R2 may be taken together to form a ring or het;
R3 and R3′ are independently H, CF3, C2F5, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, CH2—Z, or R2 and R3 taken together form het, wherein alkyl, alkenyl, alkynyl or het may be unsubstituted or substituted;
Z is H, OH, F, Cl, CH3, CH2Cl, CH2F or CH2OH;
D1 and D2 are independently C, CH, or N, wherein at least one of D1 or D2 is N;
each Q is independently H, F, Cl, Br, I, C1-C10 alkyl, C1-C10 alkoxy, aryl C1-C10 alkoxy, het C1-C10 alkoxy, OH, O—C1-C10-alkyl, (CH2)0-6—C3-C7 cycloalkyl, aryl, het, aryl C1-C10 alkyl, het C1-C10 alkyl, O—(CH2)0-6 aryl, O—(CH2)0-6 het, —OR11, C(O)R11, —C(O)N(R11)(R12), N(R11)(R12), SR11, S(O)R11, S(O)2R11, S(O)2—N(R11)(R12), NR11—C(O)—R12, or NR11—S(O)2—R12, wherein alkyl, cycloalkyl, aryl and het are unsubstituted or substituted, n is 0, 1, or 2, and independent Q's may be joined to form a 5-10 membered ring;
M is C(R4)(R5), C(O), C(S), S, S(O), S(O)2O, N(R4), or a bond;
U is selected from
(a) CON(R6)(R7), CN(R6)(R7), SOmN(R6)(R7), R4, C(R4)(R5)O(R6), C(R4)(R5) S(O)mR6, C(R4)(R5)N(R6)(R7), N(R6)(R7), O(R6), wherein m is 0, 1, or 2;
R4, R5, R6 and R7 are independently H, halo, C0-10 alkyl, C0-10 alkyl-aryl, C0-10 alkyl-het, (CH2)0-6—C3-C7cycloalkyl, (CH2)0-6—C3-C7cycloalkyl-aryl, (CR4R5)0-6—(CH)0-1(aryl)1-2, or (CR4R5)0-6—(CH)0-1(het)1-2, wherein independent R4, R5, R6, and R7 may be substituted or unsubstituted and may be joined to form a 4-10 membered ring;
or
(b)
wherein A is an aromatic ring, a 5-7 het or an 8-12 membered fused ring system that may include an aromatic ring, or one 5-7 het containing 1, 2, or 3 heteroring atoms selected from N, O and S, which any position of the rings is unsubstituted or substituted with one or more Q′ s;
D is selected from:
(a) a bond, —CO—, —C(O)—C1-7 alkylene or arylene, —CF2—, —O—, —S(O)m, 1,3-dioxolane, C1-7 alkyl-OH, where alkyl, alkylene or arylene may be unsubstituted or substituted with one or more halogens, OH, —O—C1-C6alkyl, —S—C1-C6alkyl or —CF3 wherein m is 0, 1, or 2;
or
(b) —N(R15) wherein R15 is H, C1-7 alkyl which may be unsubstituted or substituted, aryl, het, —O(C1-7cycloalkyl) which may be unsubstituted or substituted, O(C1-7alkyl) which may be unsubstituted or substituted, C(O)—C1-C10alkyl, C(O)—Co—C10alkyl-aryl, C(O)C1-C10alkyl, C—(O)—Co—C10alkyl-het, SO2—C1-C10-alkyl, SO2—(Co—C10-alkylaryl), or SO2—(Co—C10-alkylhet);
Each Y is independently H, F, C1-C10 alkyl, C1-C10 alkoxy, aryl C1-C10 alkoxy, het C1-C10 alkoxy, OH, O—C1-C10-alkyl, (CH2)0-6—C3-C7 cycloalkyl, aryl, het, aryl C1-C10 alkyl, het C1-C10 alkyl, O—(CH2)0-6 aryl, (CH2)1-6 aryl, (CH2)1-6het, O—(CH2)0-6het, —OR11, C(O)R11, —C(O)N(R11)(R12), MR11)(R12), SR11, S(O)R11, S(O)2R11, S(O)2—N(R11)(R12), or NR11—S(O)2—(R12), wherein alkyl, cycloalkyl aryl, het are unsubstituted or substituted;
Each p is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
Q together with R4, R6 or Y may form a ring;
X is H, aryl, cycloalkyl, het, or an 8-12 membered fused ring system that may include an aromatic ring, or one 5-7 het containing 1, 2, or 3 heteroring atoms selected from N, O and S, in which any may substituted or unsubstituted, in which substituents on aryl, cycloalkyl and het are alkyl, halo, lower alkoxy, N(R5)R6, CN, NO2, O Q together with R4, R6 or Y may form a ring R5, S(O)yR5, C(O)N(R5)R6, S(O)yN(R5)R6;
N(R5)C(O)R6, or N(R5)S(O)yR6, wherein y is 0, 1, or 2;
het is a 5-7 membered monocyclic heterocyclic ring which may be aromatic or non-aromatic, containing 1-4 heteroring atoms selected from N, O, and S;
or an 8-12 membered fused ring system that includes one 5-7 membered heterocyclic ring which may be aromatic or non-aromatic, containing 1, 2, or 3 heteroring atoms selected from N, O and S, which het is unsubstituted or substituted;
R11 and R12 are independently H, C1-C10 alkyl, (CH2)0-6—C3-C7cycloalkyl, (CH2)0-6—(CH)0-1(aryl)1-2;
C(O)—C1-C10alkyl, —C(O)—(CH2)1-6—C3-C7cycloalkyl, —C(O)—O—(CH2)0-6-aryl, —C(O)—(CH2)0-6—O-fluorenyl, C(O)—NH—(CH2)0-6-aryl, C(O)—(CH2)0-6-aryl, C(O)—(CH2)1-6-het, —C(S)—C1-C10—C(S)—(CH2)1-6—C3-C7cycloalkyl, —C(S)—O—(CH2)0-6-aryl, —C(S)—(CH2)0-6—O-fluorenyl, C(S)—NH—(CH2)0-6-aryl, —C(S)—(CH2)0-6-aryl, C(S)—(CH2)1-6-het, C(O)R11, C(O)NR11R12, C(O)OR11, S(O)mR11, S(O)mNR11R12, C(S)R11;
C(S)NR11R12, or C(S)OR11, and m=0, 1 or 2, wherein alkyl, cycloalkyl and aryl are unsubstituted or substituted;
or R11 and R12 are a substituent that facilitates transport of the molecule across a cell membrane;
or R11 and R12 together with the nitrogen atom form het;
wherein the alkyl substituents of R1, and R12 may be unsubstituted or substituted by one or more substituents selected from C1-C10alkyl, halogen, OH, O—C1-C6alkyl, —S—C1-C6alkyl, CF3 or NR11R12;
substituted cycloalkyl substituents of R11 and R12 are substituted by one or more substituents selected from a C2-C10 alkene, C1-C6alkyl, halogen, OH, O—C1-C6alkyl, S—C1-C6alkyl, CF3, or NR11R12;
and
substituted het or substituted aryl of R11 and R12 are substituted by one or more substituents selected from halogen, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, nitro, CN, O—C(O)—C1-C4alkyl, or C(O)—O—C1-C4-alkyl;
wherein the substituents on R1, R2, R3, R4, R5, R6, R7, Q, A, and X groups are independently halo, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, lower alkanoyl, lower alkoxy, aryl, aryl lower alkyl, amino, amino lower alkyl, diloweralkylamino, lower alkanoyl, amino lower alkoxy, nitro, cyano, cyano lower alkyl, carboxy, lower carbalkoxy, lower alkanoyl, aryloyl, lower arylalkanoyl, carbamoyl, N-mono- or N,N-dilower alkyl carbamoyl, lower alkyl carbamic acid ester, amidino, guanidine, ureido, mercapto, sulfo, lower alkylthio, sulfoamino, sulfonamide, benzosulfonamide, sulfonate, sulfanyl lower alkyl, aryl sulfonamide, halogen substituted aryl sulfonate, lower alkylsulfinyl, arylsulfinyl;
aryl-lower alkylsulfinyl, lower alkylarylsulfinyl, lower alkyl-sulfonyl, arylsulfonyl, aryl-lower alkylsulfonyl, lower alkylarylsulfinyl, lower alkyl-sulfonyl, arylsulfonyl, aryl-lower alkylsulfonyl, lower aryl alkyl lower alkylarylsulfonyl, halogen-lower alkylmercapto, halogen-lower alkylsulfonyl, phosphono (—P(═O)(OH)2), hydroxy-lower alkoxy phosphoryl or di-lower alkoxyphosphoryl, (R9)NC(O)—NR10R13, lower alkyl carbamic acid ester or carbamates or —NR8R14, wherein R8 and R14 can be the same or different and are independently H or lower alkyl, or R8 and R14 together with the N atom form a 3- to 8-membered heterocyclic ring containing a nitrogen heteroring atoms and may optionally contain one or two additional heteroring atoms selected from nitrogen, oxygen and sulfur, which heterocyclic ring may be unsubstituted or substituted with lower alkyl, halo, lower alkenyl, lower alkynyl, hydroxy, lower alkoxy, nitro, amino, lower alkyl, amino, diloweralkyl amino, cyano, carboxy, lower carbalkoxy, formyl, lower alkanoyl, oxo, carbarmoyl, N-lower or N,N-dilower alkyl carbamoyl, mercapto, or lower alkylthio, and R9, R10, and R13 are independently hydrogen, lower alkyl, halogen substituted lower alkyl, aryl, aryl lower alkyl, halogen substituted aryl, halogen substituted aryl lower alkyl.

34 more elements

A compound selected from:

(S)—N-(5-(4-Fluoro-phenyl)-3-oxo-4-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-3,4-dihydro-pyrazin-2-yl)-2-methylamino-propionamide;
(S)—N-(2-(4-Fluoro-phenyl)-6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-1,6-dihydro-pyrimidin-5-yl)-2-methylamino-propionamide;
(S)—N-{5-(4-Fluoro-phenyl)-4-[2-((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-amino)-acetyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{5-(4-Fluoro-phenyl)-4-[2-((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-amino)-ethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{2-(4-Fluoro-phenyl)-1-[2-((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-amino)-acetyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N,N-dimethyl-benzamide;
(S)—N-{2-(3-Cyano-phenyl)-1-[3-(4-fluoro-benzoyl)-5-morpholin-4-yl-benzyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{5-(3-Cyano-phenyl)-4-[3-(4-fluoro-benzoyl)-5-morpholin-4-yl-benzyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{2-Cyclohex-1-enyl-1-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{2-(3-Cyano-phenyl)-1-[5-(5-fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{5-(3-Cyano-phenyl)-4-[5-(5-fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-morpholin-4-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-morpholin-4-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
N-Ethyl-3-[1-[3-(4-fluoro-benzoyl)-5-morpholin-4-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-morpholin-4-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-isobutyl-benzamide;
(S)—N-{5-(3-Acetylamino-phenyl)-4-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-6-oxo-2-o-tolyl-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-3-oxo-5-o-tolyl-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-2-o-tolyl-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-5-o-tolyl-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{2-(4-Fluoro-phenyl)-1-[2-((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-amino)-ethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-[4-[(4-Fluoro-benzylcarbamoyl)-methyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[(4-Fluoro-benzylcarbamoyl)-methyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-[4-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-[4-[5-(4-Fluoro-benzoyl)-pyridin-3-yl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[5-(4-Fluoro-benzoyl)-pyridin-3-yl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-(5-(4-Fluoro-phenyl)-4-{5-[(4-fluoro-phenyl)-methyl-amino]-pyridin-3-ylmethyl}-3-oxo-3,4-dihydro-pyrazin-2-yl)-2-methylamino-propionamide;
(S)—N-(2-(4-Fluoro-phenyl)-1-{5-[(4-fluoro-phenyl)-methyl-amino]-pyridin-3-ylmethyl}-6-oxo-1,6-dihydro-pyrimidin-5-yl)-2-methylamino-propionamide;
(S)—N-[4-[5-(5-Fluoro-2,3-dihydro-indol-1-yl)-pyridin-3-ylmethyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[5-(5-Fluoro-2,3-dihydro-indol-1yl)-pyridin-3-ylmethyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-[4-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-{5-(4-Fluoro-phenyl)-4-[1-(4-fluoro-phenyl)-1H-indol-4-ylmethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{2-(4-Fluoro-phenyl)-1-[1-(4-fluoro-phenyl)-1H-indol-4-ylmethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-[4-(5-Benzo[1,3]dioxol-5-yl-pyridin-3-ylmethyl)-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-(5-Benzo[1,3]dioxol-5-yl-pyridin-3-ylmethyl)-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-[4-[5-(4-Fluoro-phenoxy)-pyridin-3-ylmethyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[5-(4-Fluoro-phenoxy)-pyridin-3-ylmethyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-{4-[4-(4-Fluoro-benzoyl)-thiazol-2-ylmethyl]-3-oxo-5-phenyl-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-[4-[4-(4-Fluoro-benzoyl)-thiazol-2-ylmethyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[4-(4-Fluoro-benzoyl)-thiazol-2-ylmethyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-{1-[4-(4-Fluoro-benzoyl)-thiazol-2-ylmethyl]-6-oxo-2-phenyl-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)-2-Methylamino-N-(6-oxo-2-phenyl-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-1,6-dihydro-pyrimidin-5-yl)-propionamide;
(S)-2-Methylamino-N-(3-oxo-5-phenyl-4-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-3,4-dihydro-pyrazin-2-yl)-propionamide;
(S)—N-(2-(3-Trifluoromethyl-phenyl)-6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-1,6-dihydro-pyrimidin-5-yl)-2-methylamino-propionamide;
(S)—N-(5-(3-Trifluoromethyl-phenyl)-3-oxo-4-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoy]-methyl}-3,4-dihydro-pyrazin-2-yl)-2-methylamino-propionamide;
(S)—N-{2-(4-Fluoro-phenyl)-1-[((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-carbamoyl)-methyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{5-(4-Fluoro-phenyl)-4-[((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-carbamoyl)-methyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)-2-Methylamino-N-(6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-2-o-tolyl-1,6-dihydro-pyrimidin-5-yl)-propionamide;
(S)-2-Methylamino-N-(3-oxo-4-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-5-o-tolyl-3,4-dihydro-pyrazin-2-yl)-propionamide;
(S)—N-(2-(4-Fluoro-2-methyl-phenyl)-6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yOcarbamoyl]-methyl}-1,6-dihydro-pyrimidin-5-yl)-2-methylamino-propionamide;
(S)—N-(5-(4-Fluoro-2-methyl-phenyl)-3-oxo-4-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-3,4-dihydro-pyrazin-2-yl)-2-methylamino-propionamide;
(S)—N-(2-(2,4-Dimethyl-phenyl)-6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-1,6-dihydro-pyrimidin-5-yl)-2-methylamino-propionamide;
(S)—N-(5-(2,4-Dimethyl-phenyl)-3-oxo-4-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-3,4-dihydro-pyrazin-2-yl)-2-methylamino-propionamide;
(S)—N-(2-(4-Fluoro-2-methyl-phenyl)-6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-1,6-dihydro-pyrimidin-5-yl)-2-methylamino-butyramide;
(S)—N-(5-(4-Fluoro-2-methyl-phenyl)-3-oxo-4-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-3,4-dihydro-pyrazin-2-yl)-2-methylamino-butyramide;
(S)—N-(2-(4-Cyano-phenyl)-6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-1,6-dihydro-pyrimidin-5-yl)-2-methylamino-propionamide;
N-Methyl-3-(5-((S)-2-methylamino-propionylamino)-6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-1,6-dihydro-pyrimidin-2-yl)-benzamide;
N,N-Dimethyl-3-(5-((S)-2-methylamino-propionylamino)-6-oxo-1-{[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-methyl}-1,6-dihydro-pyrimidin-2-yl)-benzamide;
(S)—N-(2-(4-Fluoro-phenyl)-1-{[2-(4-fluoro-phenyl)-ethylcarbamoyl]-methyl}-6-oxo-1,6-dihydro-pyrimidin-5-yl)-2-methylamino-propionamide;
(S)—N-[1-[(1-Benzyl-2-phenyl-ethylcarbamoyl)-methyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-[4-[(1-Benzyl-2-phenyl-ethylcarbamoyl)-methyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[(Diphenethylcarbamoyl)-methyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-[4-[(Diphenethylcarbamoyl)-methyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[4-(2-Carbazol-9-yl-2-oxo-ethyl)-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-[4-(2-Carbazol-9-yl-2-oxo-ethyl)-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[4-[2-(1,3-Dihydro-isoindol-2-yl)-2-oxo-ethyl]-5-(4-fluoro-phenyl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-[1-[2-(1,3-Dihydro-isoindol-2-yl)-2-oxo-ethyl]-2-(4-fluoro-phenyl)-6-oxo-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-{2-(4-Fluoro-phenyl)-1-[2-(indan-2-yloxy)-ethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{5-(4-Fluoro-phenyl)-4-[2-(indan-2-yloxy)-ethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-[2-(4-Fluoro-phenyl)-6-oxo-1-(2-phenethylsulfanyl-ethyl)-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-{2-(4-Fluoro-phenyl)-6-oxo-1-[2-(2-phenyl-ethanesulfonyl)-ethyl]-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{2-Benzo[1,3]dioxol-5-yl-1-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{5-Benzo[1,3]dioxol-5-yl-4-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
(S)—N-[4-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-5-(4-methoxy-pyridin-3-yl)-3-oxo-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-{2-Benzo[1,2,5]oxadiazol-5-yl-1-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{5-Benzo[1,2,5]oxadiazol-5-yl-4-[5-(4-fluoro-benzoyl)-pyridin-3-ylmethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{2-Benzo[1,2,5]oxadiazol-5-yl-1-[5-(5-fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{5-Benzo[1,2,5]oxadiazol-5-yl-4-[5-(5-fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(4-Fluoro-benzoyl)-pyridin-3-ylmethyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
[5-((S)-2-Methylamino-propionylamino)-6-oxo-2-phenyl-6H-pyrimidin-1-yl]-acetic acid 1,2,3,4-tetrahydro-naphthalen-1-yl ester;
[3-((S)-2-Methylamino-propionylamino)-2-oxo-6-phenyl-2H-pyrazin-1-yl]-acetic acid 1,2,3,4-tetrahydro-naphthalen-1-yl ester;
(S)—N-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-2-(2-pyrrolidin-1-yl-pyridin-4-yl)-1,6-dihydro-pyrimidin-5-yl]-2-methylamino-propionamide;
(S)—N-[4-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-5-(2-pyrrolidin-1-yl-pyridin-4-yl)-3,4-dihydro-pyrazin-2-yl]-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-2-phenyl-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-5-phenyl-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-2-phenyl-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-5-phenyl-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-2-[3-(2H-tetrazol-5-yl)-phenyl]-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-2-[4-(1H-tetrazol-5-yl)-phenyl]-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-5-[3-(2H-tetrazol-5-yl)-phenyl]-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-5-[4-(1H-tetrazol-5-yl)-phenyl]-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-2-[3-(2-methyl-2H-tetrazol-5-yl)-phenyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-[3-(2-methyl-2H-tetrazol-5-yl)-phenyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-2-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-2-[3-(1H-[1,2,3]triazol-4-yl)-phenyl]-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-2-[4-(3H-[1,2,3]triazol-4-yl)-phenyl]-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-5-[3-(1H-[1,2,3]triazol-4-yl)-phenyl]-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{4-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-3-oxo-5-[4-(3H-[1,2,3]triazol-4-yl)-phenyl]-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
3-[1-[6-(5-Fluoro-3-methyl-indol-1-yl)-2-methyl-pyrimidin-4-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[6-(5-Fluoro-3-methyl-indol-1-yl)-2-methyl-pyrimidin-4-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[6-(5-Fluoro-3-methyl-indol-1-yl)-2-methyl-pyrimidin-4-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[5-Fluoro-3-methyl-indol-1-yl)-2-methyl-pyrimidin-4-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-{5-((R)-3-Fluoro-2-methylamino-propionylamino)-1-[5-(5-fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-1,6-dihydro-pyrimidin-2-yl}-N,N-dimethyl-benzamide;
3-{5-((R)-3-Fluoro-2-methylamino-propionylamino)-1-[5-(5-fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-6-oxo-1,6-dihydro-pyrazin-2-yl}-N,N-dimethyl-benzamide;
(R)—N-{2-(3-Cyano-phenyl)-1-[3-(4-fluoro-benzoyl)-5-morpholin-4-yl-benzyl]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-3-fluoro-2-methylamino-propionamide;
(R)—N-{5-(3-Cyano-phenyl)-4-[3-(4-fluoro-benzoyl)-5-morpholin-4-yl-benzyl]-3-oxo-3,4-dihydro-pyrazin-2-yl}-3-fluoro-2-methylamino-propionamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-1-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-Fluoro-5-(5-fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-Fluoro-5-(5-fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(5-fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(5-fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[3-Fluoro-5-(5-fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[3-Fluoro-5-(5-fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(5-fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(5-fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-trifluoromethyl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-trifluoromethyl-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[5-(5-Fluoro-3-methyl-indol-1-yl)-pyridin-3-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[6-(5-Fluoro-3-methyl-indol-1-yl)-2-methyl-pyrimidin-4-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[6-(5-Fluoro-3-methyl-indol-1-yl)-2-methyl-pyrimidin-4-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[6-(5-Fluoro-3-methyl-indol-1-yl)-2-methyl-pyrimidin-4-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-2-methyl-pyrimidin-4-ylmethyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-isopropyl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-isopropyl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-isopropyl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-isopropyl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N,N-trimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N,N-trimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N,N-trimethyl-benzamide;
3-[1-[3-(5-Fluoro-3-methyl-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N,N-trimethyl-benzamide;
3-[1-[3-Fluoro-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-Fluoro-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-Fluoro-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-Fluoro-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-Fluoro-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N,N-trimethyl-benzamide;
3-[1-[3-Fluoro-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N,N-trimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N,N-trimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(4-fluoro-benzoyl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N,N-trimethyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-2,N-dimethyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-(4-Fluoro-benzoyl)-5-pyrrolidin-1-yl-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-4,N-dimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(5-fluoro-2,3-dihydro-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N-methyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(5-fluoro-2,3-dihydro-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N-methyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(5-fluoro-2,3-dihydro-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrimidin-2-yl]-N,N-dimethyl-benzamide;
3-[1-[3-Trifluoromethyl-5-(5-fluoro-2,3-dihydro-indol-1-yl)-benzyl]-5-((S)-2-methylamino-propionylamino)-6-oxo-1,6-dihydro-pyrazin-2-yl]-N,N-dimethyl-benzamide;
(S)—N-{1-[3-Fluoro-5-(5-fluoro-2,3-dihydro-indol-1-yl)-benzyl]-6-oxo-2-o-tolyl-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
(S)—N-{4-[3-Fluoro-5-(5-fluoro-2,3-dihydro-indol-1-yl)-benzyl]-3-oxo-5-o-tolyl-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;
(S)—N-{1-[3-Fluoro-5-(4-fluoro-phenoxy)-benzyl]-6-oxo-2-o-tolyl-1,6-dihydro-pyrimidin-5-yl}-2-methylamino-propionamide;
or
(S)—N-{4-[3-Fluoro-5-(4-fluoro-phenoxy)-benzyl]-3-oxo-5-o-tolyl-3,4-dihydro-pyrazin-2-yl}-2-methylamino-propionamide;

181 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/518,184Filed 7 Dec 2007
Priority: 7 Dec 2006
Published: 30 Sep 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07D 241/20
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07D 239/47
Two or more oxygen, sulphur or nitrogen atoms: one nitrogen atom and one oxygen or sulfur atom, e.g. cytosine

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Application60/873,436Us provisional application · filed 7 Dec 2006
US 8,048,886 B2Related patent
US 2010/0249405 A1This patent

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

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A compound of formula I:

and pharmaceutically acceptable salts thereof, wherein
R1 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl or C3-C10 cycloalkyl, which R1 may be unsubstituted or substituted;
R2 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, or C3-C10 cycloalkyl, which R2 may be unsubstituted or substituted;
R1 and R2 may be taken together to form a ring or het;
R3 and R3′ are independently H, CF3, C2F5, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, CH2—Z, or R2 and R3 taken together form het, wherein alkyl, alkenyl, alkynyl or het may be unsubstituted or substituted;
Z is H, OH, F, Cl, CH3, CH2Cl, CH2F or CH2OH;
D1 and D2 are independently C, CH, or N, wherein at least one of D1 or D2 is N;
each Q is independently H, F, Cl, Br, I, C1-C10 alkyl, C1-C10 alkoxy, aryl C1-C10 alkoxy, het C1-C10 alkoxy, OH, O—C1-C10-alkyl, (CH2)0-6—C3-C7 cycloalkyl, aryl, het, aryl C1-C10 alkyl, het C1-C10 alkyl, O—(CH2)0-6 aryl, O—(CH2)0-6 het, —OR11, C(O)R11, —C(O)N(R11)(R12), N(R11)(R12), SR11, S(O)R11, S(O)2R11, S(O)2—N(R11)(R12), NR11—C(O)—R12, or NR11—S(O)2—R12, wherein alkyl, cycloalkyl, aryl and het are unsubstituted or substituted, n is 0, 1, or 2, and independent Q's may be joined to form a 5-10 membered ring;
M is C(R4)(R5), C(O), C(S), S, S(O), S(O)2O, N(R4), or a bond;
U is selected from
(a) CON(R6)(R7), CN(R6)(R7), SOmN(R6)(R7), R4, C(R4)(R5)O(R6), C(R4)(R5) S(O)mR6, C(R4)(R5)N(R6)(R7), N(R6)(R7), O(R6), wherein m is 0, 1, or 2;
R4, R5, R6 and R7 are independently H, halo, C0-10 alkyl, C0-10 alkyl-aryl, C0-10 alkyl-het, (CH2)0-6—C3-C7cycloalkyl, (CH2)0-6—C3-C7cycloalkyl-aryl, (CR4R5)0-6—(CH)0-1(aryl)1-2, or (CR4R5)0-6—(CH)0-1(het)1-2, wherein independent R4, R5, R6, and R7 may be substituted or unsubstituted and may be joined to form a 4-10 membered ring;
or
(b)
wherein A is an aromatic ring, a 5-7 het or an 8-12 membered fused ring system that may include an aromatic ring, or one 5-7 het containing 1, 2, or 3 heteroring atoms selected from N, O and S, which any position of the rings is unsubstituted or substituted with one or more Q′ s;
D is selected from:
(a) a bond, —CO—, —C(O)—C1-7 alkylene or arylene, —CF2—, —O—, —S(O)m, 1,3-dioxolane, C1-7 alkyl-OH, where alkyl, alkylene or arylene may be unsubstituted or substituted with one or more halogens, OH, —O—C1-C6alkyl, —S—C1-C6alkyl or —CF3 wherein m is 0, 1, or 2;
or
(b) —N(R15) wherein R15 is H, C1-7 alkyl which may be unsubstituted or substituted, aryl, het, —O(C1-7cycloalkyl) which may be unsubstituted or substituted, O(C1-7alkyl) which may be unsubstituted or substituted, C(O)—C1-C10alkyl, C(O)—Co—C10alkyl-aryl, C(O)C1-C10alkyl, C—(O)—Co—C10alkyl-het, SO2—C1-C10-alkyl, SO2—(Co—C10-alkylaryl), or SO2—(Co—C10-alkylhet);
Each Y is independently H, F, C1-C10 alkyl, C1-C10 alkoxy, aryl C1-C10 alkoxy, het C1-C10 alkoxy, OH, O—C1-C10-alkyl, (CH2)0-6—C3-C7 cycloalkyl, aryl, het, aryl C1-C10 alkyl, het C1-C10 alkyl, O—(CH2)0-6 aryl, (CH2)1-6 aryl, (CH2)1-6het, O—(CH2)0-6het, —OR11, C(O)R11, —C(O)N(R11)(R12), MR11)(R12), SR11, S(O)R11, S(O)2R11, S(O)2—N(R11)(R12), or NR11—S(O)2—(R12), wherein alkyl, cycloalkyl aryl, het are unsubstituted or substituted;
Each p is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
Q together with R4, R6 or Y may form a ring;
X is H, aryl, cycloalkyl, het, or an 8-12 membered fused ring system that may include an aromatic ring, or one 5-7 het containing 1, 2, or 3 heteroring atoms selected from N, O and S, in which any may substituted or unsubstituted, in which substituents on aryl, cycloalkyl and het are alkyl, halo, lower alkoxy, N(R5)R6, CN, NO2, O Q together with R4, R6 or Y may form a ring R5, S(O)yR5, C(O)N(R5)R6, S(O)yN(R5)R6;
N(R5)C(O)R6, or N(R5)S(O)yR6, wherein y is 0, 1, or 2;
het is a 5-7 membered monocyclic heterocyclic ring which may be aromatic or non-aromatic, containing 1-4 heteroring atoms selected from N, O, and S;
or an 8-12 membered fused ring system that includes one 5-7 membered heterocyclic ring which may be aromatic or non-aromatic, containing 1, 2, or 3 heteroring atoms selected from N, O and S, which het is unsubstituted or substituted;
R11 and R12 are independently H, C1-C10 alkyl, (CH2)0-6—C3-C7cycloalkyl, (CH2)0-6—(CH)0-1(aryl)1-2;
C(O)—C1-C10alkyl, —C(O)—(CH2)1-6—C3-C7cycloalkyl, —C(O)—O—(CH2)0-6-aryl, —C(O)—(CH2)0-6—O-fluorenyl, C(O)—NH—(CH2)0-6-aryl, C(O)—(CH2)0-6-aryl, C(O)—(CH2)1-6-het, —C(S)—C1-C10—C(S)—(CH2)1-6—C3-C7cycloalkyl, —C(S)—O—(CH2)0-6-aryl, —C(S)—(CH2)0-6—O-fluorenyl, C(S)—NH—(CH2)0-6-aryl, —C(S)—(CH2)0-6-aryl, C(S)—(CH2)1-6-het, C(O)R11, C(O)NR11R12, C(O)OR11, S(O)mR11, S(O)mNR11R12, C(S)R11;
C(S)NR11R12, or C(S)OR11, and m=0, 1 or 2, wherein alkyl, cycloalkyl and aryl are unsubstituted or substituted;
or R11 and R12 are a substituent that facilitates transport of the molecule across a cell membrane;
or R11 and R12 together with the nitrogen atom form het;
wherein the alkyl substituents of R1, and R12 may be unsubstituted or substituted by one or more substituents selected from C1-C10alkyl, halogen, OH, O—C1-C6alkyl, —S—C1-C6alkyl, CF3 or NR11R12;
substituted cycloalkyl substituents of R11 and R12 are substituted by one or more substituents selected from a C2-C10 alkene, C1-C6alkyl, halogen, OH, O—C1-C6alkyl, S—C1-C6alkyl, CF3, or NR11R12;
and
substituted het or substituted aryl of R11 and R12 are substituted by one or more substituents selected from halogen, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, nitro, CN, O—C(O)—C1-C4alkyl, or C(O)—O—C1-C4-alkyl;
wherein the substituents on R1, R2, R3, R4, R5, R6, R7, Q, A, and X groups are independently halo, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, lower alkanoyl, lower alkoxy, aryl, aryl lower alkyl, amino, amino lower alkyl, diloweralkylamino, lower alkanoyl, amino lower alkoxy, nitro, cyano, cyano lower alkyl, carboxy, lower carbalkoxy, lower alkanoyl, aryloyl, lower arylalkanoyl, carbamoyl, N-mono- or N,N-dilower alkyl carbamoyl, lower alkyl carbamic acid ester, amidino, guanidine, ureido, mercapto, sulfo, lower alkylthio, sulfoamino, sulfonamide, benzosulfonamide, sulfonate, sulfanyl lower alkyl, aryl sulfonamide, halogen substituted aryl sulfonate, lower alkylsulfinyl, arylsulfinyl;
aryl-lower alkylsulfinyl, lower alkylarylsulfinyl, lower alkyl-sulfonyl, arylsulfonyl, aryl-lower alkylsulfonyl, lower alkylarylsulfinyl, lower alkyl-sulfonyl, arylsulfonyl, aryl-lower alkylsulfonyl, lower aryl alkyl lower alkylarylsulfonyl, halogen-lower alkylmercapto, halogen-lower alkylsulfonyl, phosphono (—P(═O)(OH)2), hydroxy-lower alkoxy phosphoryl or di-lower alkoxyphosphoryl, (R9)NC(O)—NR10R13, lower alkyl carbamic acid ester or carbamates or —NR8R14, wherein R8 and R14 can be the same or different and are independently H or lower alkyl, or R8 and R14 together with the N atom form a 3- to 8-membered heterocyclic ring containing a nitrogen heteroring atoms and may optionally contain one or two additional heteroring atoms selected from nitrogen, oxygen and sulfur, which heterocyclic ring may be unsubstituted or substituted with lower alkyl, halo, lower alkenyl, lower alkynyl, hydroxy, lower alkoxy, nitro, amino, lower alkyl, amino, diloweralkyl amino, cyano, carboxy, lower carbalkoxy, formyl, lower alkanoyl, oxo, carbarmoyl, N-lower or N,N-dilower alkyl carbamoyl, mercapto, or lower alkylthio, and R9, R10, and R13 are independently hydrogen, lower alkyl, halogen substituted lower alkyl, aryl, aryl lower alkyl, halogen substituted aryl, halogen substituted aryl lower alkyl.

34 more elements

Facts

Application

12/518,184Filed 7 Dec 2007

Priority

7 Dec 2006

Published

30 Sep 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07D 241/20
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07D 239/47
Two or more oxygen, sulphur or nitrogen atoms: one nitrogen atom and one oxygen or sulfur atom, e.g. cytosine