Substituted piperazines and methods of use
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Abstract
Selected substituted piperazine compounds are effective for prophylaxis and treatment of diseases, such as obesity and the like. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving activation of the melanocortin receptor. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
51 Citations
28 Claims
-
1. A compound of Formula I
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 23, 24, 25, 26, 27, 28)
-
2. Compound of claim 1 wherein Y is —
- NH—
or —
CH2—
;
wherein R is selected from a) —
(CH2)n—
C3-8-cycloalkyl,b) aryl c) unsubstituted benzyl, and d) —
(CH2)n-4-10-membered heterocyclyl;
wherein the cycloalkyl and aryl groups are optionally substituted with 1 to 3 groups selected from R4; and
the heterocyclyl group is optionally substituted with 1 to 3 groups selected from R4 and oxo;
wherein R R1a, R1b, R1c, R1d, R1e, and R1f are independently selected from R4;
or wherein R1a and R1b, or R1d and R1c form oxo;
or wherein R1e and R1c form an C1-4-alkylenyl or C2-4-alkenylenyl bridge;
or wherein R1a, R1b, R1c, and R1d together with the piperazine ring forms an optionally substituted 1,2,3,4-tetrahydro-quinoxalinyl ring;
wherein R2 is selected from a) —
(CH2)n—
C3-8-cycloalkyl,b) —
(CH2)n-aryl,c) —
(CH2)n-4-10-membered heterocyclyl,wherein the cycloalkyl and aryl groups are optionally substituted with 1 to 3 groups selected from R4; and
the heterocyclyl group is optionally substituted with 1 to 3 groups selected from R4 and oxo;
wherein R3 is independently selected from H, halo, amino, C1-6-haloalkyl, C1-6-alkyl, phenyl, C1-6-haloalkoxy and C1-6-alkoxy;
or wherein R3 is an C2-4-alkenylene bridge;
wherein R4 is selected from H, C1-6-alkyl, —
(CH2)n—
C3-6-cycloalkyl, —
(CH2)n-aryl, —
(CH2)n-4-10-membered heterocyclyl, halo, —
(CH2)n—
OR9, —
NR9SO2R7, —
N(R9)2, —
C(O)NR9R9, —
NR9C(O)R7, —
NR9CO2R7, nitro, cyano, —
(CH2)n—
C(O)R7, —
C(O)OR9, —
(CH2)n—
C(S)R7, —
(CH2)n—
C═
(NR9)R7, —
NR9C═
(NR7)N(R7)2, —
[C(R7)2]pNR9SO2R7, —
[C(R7)2]pNR9C(O)R7, —
[C(R7)2]pN(R9)2, —
SO2N(R9)2, —
S(O)mR7, —
C(R7)2SO2CF3, C1-6-hydroxyalkyl, C1-6-haloalkyl and C1-6-haloalkoxy;
wherein R5 is selected from halo, —
OR9, —
NHSO2R7, —
N(R9)2, cyano, —
COR7, —
[C(R7)2]nN(R9)2, nitro, —
SO2N(R9)2, —
S(O)mR7, C1-6-haloalkyl and C1-6-haloalkoxy;
wherein R6 is selected from phenyl, naphthyl and 6-membered heteroaryl, wherein R6 is optionally substituted with one or more R3;
wherein R7 is selected from H, C1-6-alkyl, —
(CH2)n—
C3-6-cycloalkyl, —
(CH2)n-4-10-membered heterocyclyl, —
(CH2)n-aryl, amino-C1-6-alkyl, C1-6-alkylamino, C2-6-alkenyl, C1-6-alkylthio-C1-6-alkyl, C1-6-alkylcarbonylamino-C1-6-alkyl, C1-6-alkylamino-C1-6-alkyl, C1-6-alkoxy-C1-6-alkyl and C1-6-alkoxy;
wherein R8 is selected from a) 4-10-membered heterocyclyl, b) amino-C1-6-alkyl, c) amino-C1-6-alkylamino, d) C1-6-alkylamino-C1-6-alkylamino, e) C1-6-alkylamino-C1-6-alkyl, f) arylamino-C1-6-alkyl, g) aryl-C1-6-alkylamino-C1-6-alkyl, h) 4-10-membered heterocyclyl-C1-6-alkylamino-C1-6-alkyl, i) aryl, j) C1-6-alkyl, k) aryl-C1-6-alkyl, l) heterocyclyl-C1-6-alkyl, m) C3-6-cycloalkyl-(CH2)n—
,n) —
OR9o) amino-C1-6-alkoxy, p) N-(4-10-membered heterocyclyl-C1-6-alkyl)amino, q) aryl-C1-6-alkyl where the alkyl portion is substituted with amino, hydroxy or C1-C6 alkylamino, and r) 4-10-membered heterocyclyl-C1-6-alkylenyl where the alkylenyl portion is substituted with amino, hydroxy or C1-C6 alkylamino;
wherein the cycloalkyl and aryl groups are optionally substituted with 1 to 3 groups selected from R4;
the heterocyclyl group is optionally substituted with 1 to 3 groups selected from R4 and oxo; and
the alkyl group is optionally substituted with 1 to 3 groups selected from R5;
wherein R8a is selected from a) 5-10-membered heterocyclyl, b) aryl, and c) benzyl;
wherein the aryl and heterocyclyl groups are optionally substituted with 1 to 3 radicals selected from C1-6-alkyl, halo, hydroxyl, alkoxy, amino, alkylamino, cyano, —
NHC(O)R7, —
COR7, C1-6-haloalkyl and C1-6-haloalkoxy;
wherein R9 is selected from H, C1-6-alkyl, alkenyl, C3-6-cycloalkyl-(CH2)n—
, 4-10-membered heterocyclyl-(CH2)n—
, aryl-(CH2)n—
, amino-C1-6-alkyl, C1-6-alkylcarbonylamino-C1-6-alkyl, C3-6-cycloalkylamino-C1-6-alkyl, C3-6-cycloalkyl-C1-6-alkylamino-C1-6-alkyl, 5-6-membered heteroarylamino-C1-6-alkyl, 5-6-membered heteroaryl-C1-6-alkylamino-C1-6-alkyl, arylamino-C1-6-alkyl, aryl-C1-6-alkylamino-C1-6-alkyl, 5-6-membered heteroaryloxy-C1-6-alkyl, 5-6-membered heteroaryl-C1-6-alkyloxy-C1-6-alkyl, aryl-C1-6-alkyloxy-C1-6-alkyl, aryloxy-C1-6-alkyl, C1-6-alkylthio-C1-6-alkyl, C1-6-alkylamino-C1-6-alkyl, C1-6-hydroxyalkyl and C1-6-alkoxy-C1-6-alkyl;
wherein Ra are independently selected from H, and C1-6-alkyl or the two Ra'"'"'s together form C3-4-cycloalkyl;
wherein k is 0 or 1;
wherein m is 0, 1 or 2;
wherein n is 0, 1, 2 or 3; and
wherein p is 1 or 2;
and a pharmaceutically-acceptable salt thereof.
- NH—
-
3. Compound of claim 2 wherein Y is —
- NH—
;
wherein R is phenyl optionally substituted with 1 or 2 groups selected from R4;
wherein R1a, R1b, R1c, R1d, R1e, and R1f are independently selected from R4;
or wherein R1a and R1b or R1d and R1c form oxo;
wherein R2 is selected from a) —
(CH2)n—
C3-6-cycloalkyl,b) —
(CH2)n-phenyl,c) —
(CH2)n-5-10-membered heterocyclyl, andwherein the cycloalkyl and aryl groups are optionally substituted with 1 to 3 groups selected from R4; and
the heterocyclyl group is optionally substituted with 1 to 3 groups selected from R4 and oxo;
wherein R3 is independently selected from H, chloro, bromo, iodo, phenyl, fluoro, amino, C1-2-alkyl, C1-2-haloalkyl, C1-2-haloalkoxy, and C1-2-alkoxy;
wherein R4 is selected from H, C1-2-alkyl, —
(CH2)n—
C5-6-cycloalkyl, —
(CH2)n-phenyl, —
(CH2)n-4-10-membered heterocyclyl, fluoro, chloro, —
(CH2)n—
OR9a, —
NR9aSO2R7, —
NR9aR9b, —
C(O)NR9aR9b, —
NR9aC(O)R7, —
NR9aCO2R7, cyano, nitro, —
(CH2)n—
C(O)R7, —
C(O)OR9a, —
(CH2)n—
C(S)R7, —
(CH2)n—
C═
(NR9a)R7, —
NR9aC═
(NR9a)N(R7)2, —
[C(R7)2]pNR9aR9b, —
[CH2]pNR9aSO2R7, —
[CH2]pNR9aC(O)R7, —
SO2NR9aR9b, —
S(O)mR7, —
C(R7)2SO2CF3, C1-2-hydroxyalkyl C1-2-haloalkyl and C1-2-haloalkoxy;
wherein R5 is selected from halo, —
OR9a, —
NR9aR9b, —
[C(R7)2]nNR9aR9b, and —
SO2NR9aR9b;
wherein R6 is naphthyl or phenyl optionally substituted with one or two R3;
wherein R7 is selected from C1-4-alkyl, —
(CH2)n—
C3-6-cycloalkyl, —
(CH2)n-4-10-membered heterocyclyl, —
(CH2)n-phenyl, amino-C1-4-alkyl, C1-4-alkylamino, C2-4-alkenyl, C1-4-alkylthio-C1-4-alkyl, C1-4-alkylcarbonylamino-C1-4-alkyl, C1-4-alkylamino-C1-4-alkyl, C1-4-alkoxy-C1-4-alkyl and C1-4-alkoxy;
wherein R8 is selected from a) amino-C1-4-alkylamino, b) amino-C1-4-alkyl, c) C1-4-alkylamino-C1-4-alkylamino, d) C1-4-alkylamino-C1-4-alkyl, e) phenyl-C1-4-alkylamino-C1-4-alkyl, f) phenylamino-C1-4-alkyl, g) 4-10-membered heterocyclyl-C1-4-alkylamino-C1-4-alkyl, h) N-(4-10-membered heterocyclyl-C1-4-alkyl)amino, i) C1-4-alkyl, j) C3-6-cycloalkyl-(CH2)n—
,k) aryl-(CH2)n—
,l) 4-10-membered heterocyclyl-(CH2)n—
,m) R9aO—
,n) amino-C1-4-alkoxy, o) phenyl-C1-4-alkyl where the alkyl portion is substituted with amino, hydroxy or C1-4 alkylamino, and p) 4-10-membered heterocyclyl-C1-4-alkylenyl where the alkylenyl portion is substituted with amino, hydroxy or C1-4 alkylamino;
wherein the cycloalkyl and aryl groups are optionally substituted with 1 to 3 groups selected from R4;
the heterocyclyl group is optionally substituted with 1 to 3 groups selected from R4 and oxo; and
the alkyl group is optionally substituted with 1 to 3 groups selected from R5;
wherein R9a is selected from H, C1-6-alkyl, C3-6-cycloalkyl-(CH2)n—
, 4-10-membered heterocyclyl-(CH2)n—
, and phenyl-(CH2)n—
;
wherein R9b is selected from H, C1-6-alkyl, C2-6-alkenyl, C3-6-cycloalkyl-(CH2)n—
, 4-10-membered heterocyclyl-(CH2)n—
, phenyl-(CH2)n—
, amino-C1-6-alkyl, C1-6-alkylcarbonylamino-C1-6-alkyl, C3-6-cycloalkylamino-C1-6-alkyl, C3-6-cycloalkyl-C1-6-alkylamino-C1-6-alkyl, 5-6-membered heteroarylamino-C1-6-alkyl, 5-6-membered heteroaryl-C1-6-alkylamino-C1-6-alkyl, phenylamino-C1-6-alkyl, phenyl-C1-6-alkylamino-C1-6-alkyl, 5-6-membered heteroaryloxy-C1-6-alkyl, 5-6-membered heteroaryl-C1-6-alkyloxy-C1-6-alkyl, phenyl-C1-6-alkyloxy-C1-6-alkyl, phenyloxy-C1-6-alkyl, C1-6-alkylthio-C1-6-alkyl, C1-6-alkylamino-C1-6-alkyl, C1-6-hydroxyalkyl and C1-6-alkoxy-C1-6-alkyl;
wherein Ra are independently H, or methyl;
wherein k is 1;
wherein m is 0, 1 or 2;
wherein n is 0, 1, 2 or 3;
wherein p is 1 or 2; and
wherein q is 1;
and a pharmaceutically-acceptable salt thereof.
- NH—
-
4. Compound of claim 3 wherein R is
-
5. Compound of claim 4 wherein R is
-
6. Compound of claim 3 wherein R is
-
7. Compound of claim 6 wherein R8 is
-
8. Compound of claim 7 wherein R8 is
-
9. Compound of claim 1 and pharmaceutically acceptable salts thereof selected from
quinoline-6-carboxylic acid [1-(4-chloro-benzyl)-2-(4-{2-[1-(cyclopropylmethyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide; -
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [2-(4-{2-[1-(acetyl-methyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-1-(4-chloro-benzyl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid [2-(4-{2-[1-(bis-cyclopropylmethyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-1-(4-chloro-benzyl)-2-oxo-ethyl]-amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [1-(4-chloro-benzyl)-2-(4-{2-[1-(isobutyl-methyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid [2-(4-{2-[(bis-cyclopropylmethyl-amino)methyl]phenyl}-piperazin-1-yl)-1-(4-chlorobenzyl)-2-oxo-ethyl]amide;
quinoline-6-carboxylic acid [1-(4-chlorobenzyl)-2-(4-{2-[(cyclopropylmethyl-propylamino)methyl]phenyl}-piperazin-1-yl)-2-oxo-ethyl]amide;
N-[1-(4-chlorobenzyl)-2-(4-{2-[(cyclopropylmethyl-propyl-amino)-methyl]-4-fluorophenyl}-piperazin-1-yl)-2-oxo-ethyl]-3-piperidin-1-yl-propionamide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [1-(4-chloro-benzyl)-2-(4-{2-[1-(methylsulfonylmethylamino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [2-(4-{2-[(2-aminoethyl)-methylsulfonylamino]-phenyl}-piperazin-1-yl)-1-(4-chlorobenzyl)-2-oxo-ethyl]amide;
azetidine-3-carboxylic acid {1-(4-chlorobenzyl)-2-oxo-2-[4-(2-[1,2,3]triazol-2-ylmethylphenyl)piperazin-1-yl]ethyl}amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [2-[3-[(2-aminoethylcarbamoyl)methyl]-4-(2-methylsulfonylaminophenyl)-piperazin-1-yl]-1-(4-chlorobenzyl)-2-oxo-ethyl]amide;
1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [2-[4-(2-{1-[(4-acetylaminobenzyl)methylamino]ethyl}-phenyl)-piperazin-1-yl]-1-(4-chlorobenzyl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid {1-(4-chlorobenzyl)-2-[4-(2-{1-[cyclopropylmethyl-(3-methylbutyl)amino]ethyl}-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-amide;
quinoline-6-carboxylic acid [1-(4-chlorobenzyl)-2-(4-{2-[1-(cyclohexylmethyl-cyclopropylmethyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid {1-(4-chlorobenzyl)-2-[4-(2-{1-[cyclopropylmethyl-(3-methylsulfanylpropyl)amino]-ethyl}phenyl)-piperazin-1-yl]-2-oxo-ethyl}-amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [2-{4-[4-bromo-2-(1-methylamino-ethyl)-phenyl]-piperazin-1-yl}-1-(4-chloro-benzyl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid [1-(4-chlorobenzyl)-2-(4-{2-[1-(cyclopropylmethyl-thiophen-3-ylmethylamino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid (1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)-phenyl]-piperazin-1-yl}-2-oxo-ethyl)-amide;
1-isobutyl-azetidine-3-carboxylic acid (1-(4-chloro-benzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonyl-amino)-phenyl]-piperazin-1-yl}-2-oxo-ethyl)-amide;
1-(2,2-dimethylpropyl)-azetidine-3-carboxylic acid (1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)phenyl]-piperazin-1-yl}-2-oxo-ethyl)-amide;
1-cyclopropylmethyl-azetidine-3-carboxylic acid (1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)phenyl]piperazin-1-yl}-2-oxo-ethyl)-amide;
4-benzyloxy-N-(1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)-phenyl]-piperazin-1-yl}-2-oxo-ethyl)-benzamide;
N-(1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)-phenyl]-piperazin-1-yl}-2-oxo-ethyl)-3-methylamino-propionamide;
N-(1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonyl-amino)phenyl]-piperazin-1-yl}-2-oxo-ethyl)-3,4-dimethoxybenzamide; and
piperidine-4-carboxylic acid (1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)phenyl]-piperazin-1-yl}-2-oxo-ethyl)amide.
-
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23. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a compound as in claim 1.
-
24. A method of treating obesity in a subject, said method comprising administering an effective amount of a compound of claim 1.
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25. A method of treating diabetes mellitus in a subject, said method comprising administering an effective amount of a compound of claim 1.
-
26. A method of treating disorders related to activation of a G-protein coupled receptor, in a mammal, said method comprising administering an effective amount of a compound of claim 1.
-
27. The method of claim 26 wherein the receptor is a melanocortin receptor.
-
28. The method of claim 27 wherein the melanocortin receptor is MC4R.
-
2. Compound of claim 1 wherein Y is —
-
10. A compound of formula II
- View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19)
-
11. Compound of claim 10 wherein R10 is H;
-
wherein R13a is selected from H, phenyl, bromo, chloro, trifluoromethyl and methoxy;
wherein R13b is H;
wherein R15 is selected from H and C1-2-haloalkyl;
wherein R17 is selected from H, C1-3-alkyl, —
(CH2)n—
C3-6-cycloalkyl, and —
(CH2)n-phenyl;
wherein R19 is selected from H, R23SO2—
, C1-6-alkyl, amino-C1-3-alkyl, C1-6-alkylamino-C1-3-alkyl, C3-5-cycloalkylamino-C1-3-alkyl, C3-5-cycloalkyl-C1-3-alkylamino-C1-3-alkyl, C1-3-alkylthio-C1-3-alkyl, C1-3-alkoxy-C1-3-alkyl, heteroarylamino-C1-3-alkyl, 5-6 membered heteroaryl-C1-3-alkylamino-C1-3-alkyl, phenylamino-C1-3-alkyl, phenyl-C1-3-alkylamino-C1-3-alkyl, 5-6 membered heteroaryloxy-C1-3-alkyl, phenyloxy-C1-3-alkyl, hydroxy-C1-3-alkyl, phenyl-C1-3-alkoxy-C1-3-alkyl, C1-6-alkylcarbonyl, C1-3-alkoxycarbonyl, C1-3-alkoxy-C1-3-alkylcarbonyl, C1-3-alkylaminocarbonyl, C3-6-cycloalkylcarbonyl, C3-6-cycloalkyl-C1-3-alkylcarbonyl, phenylcarbonyl, phenyl-C1-3-alkylcarbonyl, 5- or 6-membered heteroaryl-C1-3-alkylcarbonyl, 5- or 6-membered heteroarylcarbonyl and —
(CH2)n—
C3-5-cycloalkyl optionally substituted with C1-2-alkoxycarbonyl;
wherein R20 is selected from H, C1-7-alkyl, —
(CH2)n—
C5-6-cycloalkyl, —
(CH2)n-5-6-membered heterocyclyl, C1-3-alkylsulfonyl, amino-C1-3-alkyl and —
(CH2)n-phenyl;
alternatively R19 and R20 together with the nitrogen atom form a 4-8 membered heterocyclic ring;
wherein R21 is selected from H, C1-3-alkyl, C2-3-alkenyl, C1-3-alkylthio-C1-3-alkyl, C1-3-alkylcarbonylamino-C1-3-alkyl, amino-C1-3-alkyl, —
(CH2)n-[5- or 6-membered heterocyclyl], —
(CH2)n—
C5-6-cycloalkyl, and —
(CH2)n-phenyl;
wherein R22 is selected from H, C1-3-alkyl, —
(CH2)n—
C4-6-cycloalkyl, —
(CH2)n-[5- or 6-membered heterocyclyl] and —
(CH2)n-phenyl;
alternatively R21 and R22 together with the amide nitrogen atom form a 5-6 membered heterocyclic ring; and
wherein R23 is selected from H, C1-3-alkyl, —
(CH2)n—
C4-6-cycloalkyl, —
(CH2)n-[5- or 6-membered heterocyclyl] and —
(CH2)n-phenyl;
wherein phenyl and heterocyclyl are optionally substituted with one or more substituents selected from C1-2-haloalkyl, C1-2-alkyl, —
(CH2)n—
C4-6-cycloalkyl, chloro, fluoro, —
OR17, —
NR17CO2R17, —
NR17SO2R17, N(R17)2, cyano, —
COR17, —
C(R17)2N(R17)2, nitro, —
SO2N(R17)2, —
S(O)mR17, and C1-2-haloalkoxy;
and pharmaceutically-acceptable salts thereof.
-
-
12. Compound of claim 11 wherein R13a is selected from H, bromo and chloro;
-
wherein R13b is H;
wherein R14 is selected from trifluoromethyl, 2-hydroxyethyl, 1-hydroxyethyl, R19R20N—
, R19R20N—
C1-2-alkyl and (R21R22N—
)(O═
)C—
;
wherein R15 is H or trifluoromethyl;
wherein R17 is selected from H, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl, phenylpropyl, phenylethyl, benzyl and phenyl;
wherein R19 is selected from H, R23SO2—
, methyl, ethyl, propyl, isopropyl, isopentyl, 3-ethylbutyl, hydroxymethyl, hydroxyethyl, cyclopropylmethyl, 1-(ethoxycarbonyl)cycloprop-2-ylmethyl, R23 SO2—
, aminomethyl, aminoethyl, dimethylaminoethyl, diethylaminoethyl, dipropylaminoethyl, diisobutylaminoethyl, di-tert-butylmethylaminoethyl, di(3-ethylbutyl)aminoethyl, furylmethylaminoethyl, thienylmethylaminoethyl, benzylaminoethyl, di(furylmethyl)aminoethyl, di(cyclohexylmethyl)aminoethyl, di(cyclopropylmethyl)aminoethyl, di(thienylmethyl)aminoethyl, di(benzyl)aminoethyl, phenylmethoxyethyl, pyridyloxymethyl, methylthiopropyl, methylcarbonyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, isobutylcarbonyl, tert-butylcarbonyl, pentylcarbonyl, butylcarbonyl, cyclopentylcarbonyl, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclohexylcarbonyl, methoxycarbonyl, methoxymethylcarbonyl, ethoxycarbonyl, propoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, optionally substituted thienylmethylcarbonyl, optionally substituted benzylcarbonyl, optionally substituted phenylethylcarbonyl, optionally substituted phenylcarbonyl and optionally substituted pyridylcarbonyl;
wherein R20 is selected from H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropyl, cyclohexyl, methylsulfonyl, aminoethyl, optionally substituted phenyl, optionally substituted imidazolyl, optionally substituted imidazolylmethyl, optionally substituted thienylmethyl, optionally substituted furylmethyl, optionally substituted pyrrolidinylmethyl, optionally substituted pyridylmethyl, optionally substituted thienylmethyl, optionally substituted benzyl, optionally substituted phenylethyl and optionally substituted phenylpropyl;
alternatively R19 and R20 together with the nitrogen atom form a heterocyclic ring selected from triazolyl, tetrazolyl, 2-pyridone, oxo-pyrrolidinyl, 2-oxo-piperidinyl, 4,5-dihydro-2-oxo-oxazolyl, 1,1-dioxo-isothiazolidin-2-yl, 2-oxo-imidazolin-1-yl, 3-methyl-2-oxo-imidazolin-1-yl, piperidinyl optionally substituted with one or more substituents selected from methyl, ethyl, propyl, and isopropyl, piperazinyl optionally substituted with one or more substituents selected from methyl, ethyl, propyl, and isopropyl, imidazolyl optionally substituted with one or more substituents selected from methyl, ethyl, propyl, and isopropyl, and pyrrolidinyl optionally substituted with one or more substituents selected from methyl, ethyl, propyl, and isopropyl;
wherein R21 is selected from H, methyl, ethyl, propyl, isopropyl, allyl, methylthioethyl, methylthiomethyl, methylcarbonylaminoethyl, methylcarbonylaminomethyl, aminomethyl, aminoethyl, 1-methylpyrrolidinylethyl, piperidinylethyl, pyridyl, cyclopentylmethyl, cyclohexylmethyl, phenyl, 4-chlorophenylmethyl, 4-phenoxyphenylethyl, benzyl and phenylethyl;
wherein R22 is H or methyl;
alternatively R21 and R22 together form a ring selected from pyrrolidinyl, morpholino, piperidinyl, piperazinyl, 4-acetylpiperazinyl and 4-methylpiperazinyl; and
wherein R23 is selected from H, methyl, ethyl, propyl, optionally substituted thienyl, optionally substituted phenyl, optionally substituted benzyl, optionally substituted phenylethyl and optionally substituted phenylpropyl;
wherein phenyl and heterocyclyl are optionally substituted with one or more substituents selected from trifluoromethyl, methyl, nitro, cyano, chloro, methoxy, phenyloxy, acetyl, amino, dimethylamino and aminomethyl;
and pharmaceutically-acceptable salts thereof.
-
-
13. Compound of claim 12 wherein R14 is selected from N-pyrrolidinylcarbonyl, N-morpholinocarbonyl, N-piperidinylethylaminocarbonyl, benzylaminocarbonyl, N-methyl-N-benzylaminocarbonyl, aminoethylaminocarbonyl, pyridylaminocarbonyl, methylthioethylaminocarbonyl, methylcarbonylaminoethylaminocarbonyl, 1-methylpyrrolidinylethylaminocarbonyl, phenethylaminocarbonyl, phenylaminocarbonyl, cyclohexylmethylaminocarbonyl, N-methyl-N-phenethylaminocarbonyl, N,N-dimethylaminocarbonyl, 4-chlorophenylmethylaminocarbonyl, phenoxyphenethylaminocarbonyl, allylaminocarbonyl, 4-methylpiperazinylcarbonyl, 4-acetylpiperazinylcarbonyl, isopropylaminocarbonyl,
1-(N-cyclopropylmethylamino)ethyl, 1-(N-methyl-N-methylcarbonylamino)ethyl, 1-(N-isopropylamino)ethyl, 1-(N-isobutyl-N-methylamino)ethyl, N-cyclopropylmethyl-N-propylaminomethyl, N,N-dicyclopropylmethylaminomethyl, 1-(N-propyl-N-methylamino)ethyl, 1-(N-methyl-N-methylsulfonylamino)ethyl, triazolylmethyl, imidazol-1-ylmethyl, 2-isopropylimidazol-1-yl-methyl, 2-propylimidazol-1-yl-methyl, 2-oxo-pyrid-1-yl-methyl, 3-pyridyl-oxymethyl, 2-methylimidazol-1-yl-methyl, tetrazolylmethyl, 2,5-dimethylpyrrolidin-1-ylmethyl, 2-oxo-pyrrolidin-1-yl-methyl, 2-oxo-piperidin-1-yl-methyl, 4,5-dihydro-2-oxo-oxazol-3-yl-methyl, pyrrolidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, piperazin-1-yl-methyl, 4-methylpiperazin-1-yl-methyl, piperidin-1-yl-methyl, 1-(N-ethyl-N-methylamino)ethyl, 1-(N,N-dipropylamino)ethyl, 1-(N,N-diisopropylamino)ethyl, 1-(N-(1-ethoxycarbonyl)cycloprop-2-ylmethyl-N-methylamino)ethyl, 1-(N-(2-methylbutyl)-N-methylamino)ethyl, 1-(N-(4-methylcarbonylaminophenyl)methyl-N-methylamino)ethyl, 1-(N-methylamino)ethyl, 1-(N,N-dimethylamino)ethyl, N,N-dimethylaminomethyl, N-cyclopropylmethyl-N-methylsulfonylaminomethyl, 1-(N-(3-thienyl)methyl-N-methylamino)ethyl, 1-(N-phenylmethoxyethyl-N-methylamino)ethyl, 1-(N-(2-methoxyphenyl)methyl-N-methylamino)ethyl, 1-(N-(4-pyridyl)methyl-N-methylamino)ethyl, 1-(N-(2-pyrrolidinyl)methyl-N-methylamino)ethyl, 1-(N-(3-methoxyphenyl)methyl-N-methylamino)ethyl, 1-(N-(4-methoxyphenyl)methyl-N-methylamino)ethyl, 1-(N-benzyl-N-methylamino)ethyl, 1-(N-methyl-N-aminoethylamino)ethyl, 1-(N-cyclohexylmethyl-N-methylamino)ethyl, N,N-dimethylaminomethyl, N-(1-hydroxyethyl)-N-methylaminomethyl, N-(1-hydroxyethyl)-N-methylaminomethyl, N-propyl-N-methylsulfonylamino, N-(methylsulfonyl)-N-propylamino, N-(methylsulfonyl)-N-cyclopropylmethylamino, N-(methylsulfonyl)-N-aminoethylamino, N-(methylsulfonyl)-N-(N′ - ,N′
-dimethylaminoethyl)amino, N-(N′
,N′
-diethylaminoethyl)-N-methylsulfonylamino, N-(N′
,N′
-dipropylaminoethyl)-N-methylsulfonylamino, N-(N′
,N′
-diisobutylaminoethyl)-N-methylsulfonylamino, N-(N′
,N′
-di-tert-butylmethylaminoethyl)-N-methylsulfonylamino, N-(N′
,N′
-di(cyclopropylmethyl)aminoethyl)-N-methylsulfonylamino, N-(N′
,N′
-di(2-furylmethyl)aminoethyl)-N-methylsulfonylamino, N-(N′
,N′
-di(3-thienylmethyl)aminoethyl)-N-methylsulfonylamino, N-(N′
,N′
-di(benzyl)aminoethyl)-N-methylsulfonylamino, N-(methylsulfonyl)-N-isobutylamino, N-(methylsulfonyl)-N-methylamino, N-(methylsulfonyl)-N-phenethylamino, N-(methylsulfonyl)amino, N-(benzylsulfonyl)amino, N-(propylsulfonyl)amino, N-(phenylsulfonyl)amino, N-(methylsulfonyl)-N-phenylpropylamino, thienylsulfonylamino, (2-nitrophenyl)methylsulfonylamino, (2,4,6-trimethylphenyl)sulfonylamino, (2-cyanophenyl)sulfonylamino,N-methoxymethylcarbonyl-N-cyclopropylmethylamino, N-methylcarbonyl-N-cyclopropylmethylamino, N-phenylcarbonyl-N-cyclopropylmethylamino, N-(3-methoxyphenylcarbonyl-N-cyclopropylmethylamino, N-benzylcarbonyl-N-cyclopropylmethylamino, N-phenylethyl-N-cyclopropylmethylamino, N-(2-imidazolyl)-N-cyclopropylmethylamino, N-(4-methyl-5-imidazolyl)-N-cyclopropylmethylamino, N-(2-thienylmethyl)-N-cyclopropylmethylamino, N-(3-thienylmethyl)-N-cyclopropylmethylamino, N-(3-furylmethyl)-N-cyclopropylmethylamino, N-(4-imidazolyl)-N-cyclopropylmethylamino, N-cyclopentylcarbonyl-N-cyclopropylmethylamino, N-cyclohexylcarbonyl-N-cyclopropylmethylamino, N-methylthiopropyl-N-cyclopropylmethylamino, N-ethylcarbonyl-N-cyclopropylmethylamino, N-isopropylcarbonyl-N-cyclopropylmethylamino, N-isobutylcarbonyl-N-cyclopropylmethylamino, N-ethyl-N-cyclopropylmethylamino, N-isobutyl-N-cyclopropylmethylamino, N-cyclopropylcarbonyl-N-cyclopropylmethylamino, N,N-di(cyclopropylmethyl)amino, N-methoxymethylcarbonyl-N-aminoethylamino, N-ethylcarbonyl-N-aminoethylamino, N-isopropylcarbonyl-N-aminoethylamino, N-isobutylcarbonyl-N-aminoethylamino, N-tert-butylcarbonyl-N-aminoethylamino, N-propylcarbonyl-N-aminoethylamino, N-pentylcarbonyl-N-aminoethylamino, N-ethyl-N-aminoethylamino, N-propyl-N-aminoethylamino, N-cyclopropyl-N-aminoethylamino, N-cyclopropylmethyl-N-aminoethylamino, N-cyclobutylmethyl-N-aminoethylamino, N-butyl-N-aminoethylamino, N-pentyl-N-aminoethylamino, N-hexyl-N-aminoethylamino, N-heptyl-N-aminoethylamino, N-(3-ethylbutyl)-N-aminoethylamino, N-cyclohexylcarbonyl-N-aminoethylamino, N-phenylcarbonyl-N-aminoethylamino, N-(3-methoxyphenyl)carbonyl-N-aminoethylamino, N-benzylcarbonyl-N-aminoethylamino, N-phenylethylcarbonyl-N-aminoethylamino, N-pyridylcarbonyl-N-aminoethylamino, N-thienylmethyl-N-aminoethylamino, aminoethylamino, pyridylcarbonylamino, N-cyclopropylmethylamino, methylcarbonylamino, methoxycarbonylamino, trifluoromethyl, 2-hydroxyethyl, 1-hydroxyethyl, methylaminocarbonylamino, 1,1-dioxo-isothiazolidin-2-yl, 2-oxo-imidazolin-1-yl and 3-methyl-2-oxo-imidazolin-1-yl;
and pharmaceutically-acceptable salts thereof.
- ,N′
-
14. Compound of claim 12 wherein R12 is selected from
-
15. Compound of claim 14 wherein R16 is selected from N-(piperidylmethyl)amino, aminopropylamino, aminomethyl, aminoethyl, aminopropyl, N-methylaminomethyl, N-(4-chlorophenyl)aminoethyl, N-methylaminoethyl, N,N-dimethylaminoethyl, 2-aminoethyl, aminopropoxy, pyrrolidinylmethoxy, N-methylaminoethylamino, 3-aminocyclopentyl, 4-aminocyclohexyl, 1-aminocyclohexyl, 2-indolyl, octahydro-indolyl, 1-methylindol-2-yl, 3-pyridyl, 2-pyridyl, N-methylbenzopyrrolyl, 5-benzopyrrolyl, 2-benzofuran, benzodioxolyl, 2-benzothienyl, 4-imidazolylmethyl, 3-azetidinyl optionally N-substituted with a substituent selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, cyclohexylmethyl and benzyl, 6-quinolyl, 2-quinolyl, 3-isoquinolyl, tetrahydroisoquinolyl, N-methylpyrrolidin-2-yl, pyrrolidin-2-yl, 5-oxopyrrolidin-2-yl, 3-phenylpyrrolidin-2-yl, (1-methyl-5-oxo-2-(pyridin-3-yl)-pyrrolidin-3-yl)methyl, piperidin-1-yl ethyl, thienyl, 4-piperidyl, 4-piperidylmethyl, N-methyl-4-piperidyl, N-methyl-2-piperidyl, N-ethyl-4-piperidyl, N-isobutyl-4-piperidyl, 3-piperidyl, 3-(aminomethyl)phenyl, 4-(trifluoromethyl)phenyl, 3-(trifluoromethyl)phenyl, 2-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 3,4-dichlorophenyl, 4-fluorophenyl, 3-fluorophenyl, 2-aminophenyl, 3-aminophenyl, isopropyl, 4-chlorophenylmethyl, benzyl, phenyl-2-hydroxyethyl, 1-(amino)benzyl, 2-(1,2,3,4-tetrahydronaphthyl), naphthyl, (2-benzylamino)ethyl, imidazol-4-yl-(1-amino)ethyl, phenyl-1-(methylamino)ethyl and phenyl-1-(amino)ethyl;
- and pharmaceutically-acceptable salts thereof.
-
16. Compound of claim 15 and pharmaceutically acceptable salts thereof selected from
N-[(1R)-1-[(3,4-dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide; -
N-[(1R)-1-[(3,4-dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]azetidin-3-ylcarboxamide;
((3S)(3-1,2,3,4-tetrahydroisoquinolyl))-N-[(1S)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carboxamide;
N-[(1R)-1-[(4-methoxyphenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide;
N-[(1R)-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxo-1-{[4-(trifluoromethyl)phenyl]methyl}ethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(2-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide;
N-[(1R)-1-[(3-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide;
N-[(1R)-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-1-(naphthylmethyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-2-aminoacetamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((2S)(2-piperidyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-3-aminopropanamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-2-(methylamino)acetamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](2S)-2-amino-3-phenylpropanamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-4-piperidylcarboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](2S)-2-amino-3-imidazol-4-ylpropanamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-4-aminobutanamide;
((2R)azetidin-2-yl)-N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]indol-2-ylcarboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](1-methylindol-2-yl)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](3-chlorophenyl)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](4-chlorophenyl)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](2-methylphenyl)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](4-methoxyphenyl)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](2-chlorophenyl)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](3,4-dichlorophenyl)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl][3-(trifluoromethyl)phenyl]carboxamide;
2H-benzo[d]1,3-dioxolan-5-yl-N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl][4-(trifluoromethyl)phenyl]carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-2-phenylacetamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-3-pyridylcarboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-2-pyridylcarboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-4-pyridylcarboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-2-methylpropanamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-6-quinolylcarboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]azetidin-3-ylcarboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl][3-(aminomethyl)phenyl]carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-3-piperidylcarboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](2-aminophenyl)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](1-methyl(2-piperidyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](1-methyl(4-piperidyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-3-(dimethylamino)propanamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-3-[(4-chlorophenyl)amino]propanamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)ethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[methyl(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-3-1,2,3,4-tetrahydroisoquinolylcarboxamide;
N-[(1R)-2-(4-{2-[(2-aminoethyl)(methylsulfonyl)amino]phenyl}piperazinyl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1S)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(cyclopropylmethyl)(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]azetidin-3-ylcarboxamide;
quinoline-6-carboxylic acid [1-(4-chloro-benzyl)-2-(4-{2-[1-(cyclopropylmethyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [2-(4-{2-[1-(acetyl-methyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-1-(4-chloro-benzyl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid [2-(4-{2-[1-(bis-cyclopropylmethyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-1-(4-chloro-benzyl)-2-oxo-ethyl]-amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [1-(4-chloro-benzyl)-2-(4-{2-[1-(isobutyl-methyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid [2-(4-{2-[(bis-cyclopropylmethyl-amino)methyl]phenyl}-piperazin-1-yl)-1-(4-chlorobenzyl)-2-oxo-ethyl]amide;
quinoline-6-carboxylic acid [1-(4-chlorobenzyl)-2-(4-{2-[(cyclopropylmethyl-propylamino)methyl]phenyl}-piperazin-1-yl)-2-oxo-ethyl]amide;
N-[1-(4-chlorobenzyl)-2-(4-{2-[(cyclopropylmethyl-propyl-amino)-methyl]-4-fluorophenyl}-piperazin-1-yl)-2-oxo-ethyl]-3-piperidin-1-yl-propionamide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [1-(4-chloro-benzyl)-2-(4-{2-[1-(methylsulfonylmethylamino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [2-(4-{2-[(2-aminoethyl)-methylsulfonylamino]-phenyl}-piperazin-1-yl)-1-(4-chlorobenzyl)-2-oxo-ethyl]amide;
azetidine-3-carboxylic acid {1-(4-chlorobenzyl)-2-oxo-2-[4-(2-[1,2,3]triazol-2-ylmethylphenyl)piperazin-1-yl]ethyl}amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [2-[3-[(2-aminoethylcarbamoyl)methyl]-4-(2-methylsulfonylaminophenyl)-piperazin-1-yl]-1-(4-chlorobenzyl)-2-oxo-ethyl]amide;
1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [2-[4-(2-{1-[(4-acetylaminobenzyl)methylamino]ethyl}-phenyl)-piperazin-1-yl]-1-(4-chlorobenzyl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid {1-(4-chlorobenzyl)-2-[4-(2-{1-[cyclopropylmethyl-(3-methylbutyl)amino]ethyl}-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-amide;
quinoline-6-carboxylic acid [1-(4-chlorobenzyl)-2-(4-{2-[1-(cyclohexylmethyl-cyclopropylmethyl-amino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid {1-(4-chlorobenzyl)-2-[4-(2-{1-[cyclopropylmethyl-(3-methylsulfanylpropyl)amino]-ethyl}phenyl)-piperazin-1-yl]-2-oxo-ethyl}-amide;
1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [2-{4-[4-bromo-2-(1-methylamino-ethyl)-phenyl]-piperazin-1-yl}-1-(4-chloro-benzyl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid [1-(4-chlorobenzyl)-2-(4-{2-[1-(cyclopropylmethyl-thiophen-3-ylmethylamino)-ethyl]-phenyl}-piperazin-1-yl)-2-oxo-ethyl]-amide;
quinoline-6-carboxylic acid (1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)-phenyl]-piperazin-1-yl}-2-oxo-ethyl)-amide;
1-isobutyl-azetidine-3-carboxylic acid (1-(4-chloro-benzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonyl-amino)-phenyl]-piperazin-1-yl}-2-oxo-ethyl)-amide;
1-(2,2-dimethylpropyl)-azetidine-3-carboxylic acid (1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)phenyl]-piperazin-1-yl}-2-oxo-ethyl)-amide;
1-cyclopropylmethyl-azetidine-3-carboxylic acid (1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)phenyl]piperazin-1-yl}-2-oxo-ethyl)-amide;
4-benzyloxy-N-(1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)-phenyl]-piperazin-1-yl}-2-oxo-ethyl)-benzamide;
N-(1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonylamino)-phenyl]-piperazin-1-yl}-2-oxo-ethyl)-3-methylamino-propionamide;
N-(1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methylsulfonyl-amino)phenyl]-piperazin-1-yl}-2-oxo-ethyl)-3,4-dimethoxybenzamide;
piperidine-4-carboxylic acid (1-(4-chlorobenzyl)-2-{4-[2-(cyclopropylmethyl-methanesulfonylamino)phenyl]-piperazin-1-yl}-2-oxo-ethyl)amide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(cyclopropylmethyl)(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(2-methylpropyl)(methylsulfonyl)amino]phenyl}-piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)(2-phenylethyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-{2-[(propylsulfonyl)amino]phenyl}piperazinyl)ethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-{2-[(2-thienylsulfonyl)amino]phenyl}piperazinyl)ethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[2-(4-{(2R)-2-[((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carbonylamino]-3-(4-chlorophenyl)propanoyl}piperazinyl)phenyl]-2-methylpropanamide;
N-((1R)-1-[(4-chlorophenyl)methyl]-2-{4-[2-({[(2-nitrophenyl)methyl]sulfonyl}amino)phenyl]piperazinyl}-2-oxoethyl)((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-((1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-{4-[2-(3-pyridylcarbonylamino)phenyl]piperazinyl}ethyl)((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-{2-[(phenylsulfonyl)amino]phenyl}piperazinyl)ethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-[4-(2-{[benzylsulfonyl]amino}phenyl)piperazinyl]ethyl}((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-2-(4-{2-[(2-aminoethyl)amino]phenyl}piperazinyl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
[2-(4-{(2R)-2-[((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carbonylamino]-3-(4-chlorophenyl)propanoyl}piperazinyl)phenyl]-N,N-dimethylcarboxamide;
methyl 2-(4-{(2R)-2-[((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carbonylamino]-3-(4-chlorophenyl)propanoyl}piperazinyl)benzoate;
N-((1R)-1-[(4-chlorophenyl)methyl]-2-{4-[2-(morpholin-4-ylcarbonyl)phenyl]piperazinyl}-2-oxoethyl)((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-((1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-{4-[2-(pyrrolidinylcarbonyl)phenyl]piperazinyl}ethyl)((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[N-methyl-N-benzylcarbamoyl]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-((1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-{4-[2-(N-prop-2-enylcarbamoyl)phenyl]piperazinyl}ethyl)((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-[4-(2-{[4-benzylpiperazinyl]carbonyl}phenyl)piperazinyl]ethyl}((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(4-methylpiperazinyl)carbonyl]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-(2-{[2-(4-{(2R)-2-[((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carbonylamino]-3-(4-chlorophenyl)propanoyl}piperazinyl)phenyl]carbonylamino}ethyl)acetamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[N-methyl-N-(2-phenylethyl)carbamoyl]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[N-(2-methylthioethyl)carbamoyl]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-{(1R)-1-[(4-chlorophenyl)methyl]-2-[4-(2-{N-[(4-chlorophenyl)methyl]carbamoyl}phenyl)piperazinyl]-2-oxoethyl}((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-((1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-{4-[2-(N-phenylcarbamoyl)phenyl]piperazinyl}ethyl)((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-{(1R)-1-[(4-chlorophenyl)methyl]-2-[4-(2-{N-[2-(1-methylpyrrolidin-2-yl)ethyl]carbamoyl}phenyl)piperazinyl]-2-oxoethyl}((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-2-(4-{2-[(4-acetylpiperazinyl)carbonyl]phenyl}piperazinyl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-[4-(2-{N-[2-(3-phenoxyphenyl)ethyl]carbamoyl}phenyl)piperazinyl]ethyl}((3S) (3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-{2-[N-(2-phenylethyl)carbamoyl]phenyl}piperazinyl)ethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-{2-[N-(2-piperidylethyl)carbamoyl]phenyl}piperazinyl)ethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[N-(cyclohexylmethyl)carbamoyl]phenyl}piperazinyl)-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-2-(4-{2-[N-(2-aminoethyl)carbamoyl]phenyl}piperazinyl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-2-(4-{2-[(dimethylamino)methyl]phenyl}piperazinyl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-[(1R)-2-(4-{2-[(dimethylamino)methyl]phenyl}piperazinyl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]azetidin-3-ylcarboxamide;
N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-phenylpiperazinyl)ethyl}((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-(4-(2-pyridyl)piperazinyl)ethyl}((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide;
N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-[4-(2-pyridylmethyl)piperazinyl]ethyl}-3-1,2,3,4-tetrahydroisoquinolylcarboxamide;
N-[(1R)-2-(2,5-diaza-5-{2-[(methylsulfonyl)amino]phenyl}bicyclo[2.2.1]hept-2-yl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide; and
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}(1,4-diazaperhydroepinyl))-2-oxoethyl]((3S)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide.
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17. Compound of claim 12 wherein R12 is selected from optionally substituted benzyl, and optionally substituted 5-10-membered heteroaryl;
- and wherein R13a and R13b are independently H or chloro.
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18. Compound of claim 17 wherein R12 is selected from oxazolo[5,4-b]pyridin-2-yl, oxazolo[4,5-b]pyridin-2-yl, 4-chlorobenzyl, benzoxazol-2-yl and optionally substituted benzyl.
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19. Compound of claim 18 and pharmaceutically acceptable salts thereof selected from
(2R)-3-(4-chlorophenyl)-1-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-[benzylamino]propan-1-one; -
(2R)-2-({[4-(dimethylamino)phenyl]methyl}amino)-3-(4-chlorophenyl)-1-(4-{2-[(methylsulfonyl)amino]-phenyl}piperazinyl)propan-1-one;
(2R)-3-(4-chlorophenyl)-1-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-[(2-pyridylmethyl)amino]propan-1-one;
(2R)-3-(4-chlorophenyl)-2-{[(4-chlorophenyl)methyl]amino}-1-(4-{2-[(methyl sulfonyl)amino]phenyl}piperazinyl)propan-1-one;
(2R)-2-{[((2R)-pyrrolidin-2-yl)methyl]amino}-3-(4-chlorophenyl)-1-(4-{2-[(methyl sulfonyl)amino]phenyl}-piperazinyl)propan-1-one;
(2R)-3-(4-chlorophenyl)-2-[(indol-2-ylmethyl)amino]-1-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)propan-1-one;
(2R)-2-{[((3S)(3-(1,2,3,4-tetrahydroisoquinolyl))methyl]-amino}-3-(4-chlorophenyl)-1-(4-{2-[(methylsulfonyl)amino]-phenyl}piperazinyl)propan-1-one;
(2R)-2-[(2H,3H-benzo[3,4-e]1,4-dioxin-6-ylmethyl)amino]-3-(4-chlorophenyl)-1-(4-{2-[(methylsulfonyl)amino]phenyl}-piperazinyl)propan-1-one;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl][((2R)pyrrolidin-2-yl)methoxy]carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](3-aminopropoxy)carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl][(3-aminopropyl)amino]carboxamide;
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl][(4-piperidylmethyl)amino]carboxamide; and
N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]{[2-(methylamino)ethyl]amino}carboxamide.
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11. Compound of claim 10 wherein R10 is H;
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20. A compound of formula III
- View Dependent Claims (21, 22)
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21. Compound of claim 20 wherein R10 is H;
-
wherein R12 is selected from
optionally substituted benzyl and optionally substituted 5-10-membered heterocyclyl;
wherein R13a and R13b are independently selected from H, bromo, chloro, trifluoromethyl and methoxy;
wherein R14 is selected from trifluoromethyl, 2-hydroxyethyl, 1-hydroxyethyl, R19R20N—
, R19R20N—
C1-2-alkyl and (R21R22N—
)(O═
)C—
;
wherein R15 is selected from H and C1-2-haloalkyl;
wherein R16 is selected from a) 4-6 membered saturated heterocyclyl, b) 10 membered partially saturated heterocyclyl, c) 5-10 membered heteroaryl, d) C1-3-aminoalkyl, e) C1-3-aminoalkylamino, f) C1-3-alkylamino-C1-3-alkylamino, g) C1-3-alkylamino-C1-3-alkyl, h) phenylamino-C1-3-alkyl, i) phenyl-C1-4-alkylamino-C1-3-alkyl, j) heterocyclyl-C1-3-alkylamino-C1-3-alkyl, k) phenyl, naphthyl or tetrahydronaphthyl, l) C1-3-alkyl, m) phenyl-C1-2-alkyl, n) 5-10-membered saturated or partially unsaturated heterocyclylmethyl, o) 5-6 membered heteroaryl-C1-4-alkyl, p) C5-6-cycloalkyl, q) C1-3-aminoalkoxy, r) [5- or 6-membered heterocyclyl]-C1-3-alkoxy, s) N-(5-10-membered heterocyclyl-C1-3-alkyl)amino, t) phenyl-C1-2-alkyl where the alkyl portion is substituted with amino, hydroxy or C1-3-alkylamino, and u) 5- or 6-membered heterocyclyl-C1-3-alkylenyl where the alkylenyl portion is substituted with amino, hydroxy or C1-3-alkylamino;
wherein R17 is selected from H, C1-3-alkyl, —
(CH2)n—
C3-6-cycloalkyl, and —
(CH2)n-phenyl;
wherein R19 is selected from H, R23SO2—
, C1-6-alkyl, amino-C1-3-alkyl, C1-5-alkylamino-C1-3-alkyl, C3-5-cycloalkylamino-C1-3-alkyl, C3-5-cycloalkyl-C1-3-alkylamino-C1-3-alkyl, C1-3-alkylthio-C1-3-alkyl, C1-3-alkoxy-C1-3-alkyl, heteroarylamino-C1-3-alkyl, 5-6 membered heteroaryl-C1-3-alkylamino-C1-3-alkyl, phenylamino-C1-3-alkyl, phenyl-C1-3-alkylamino-C1-3-alkyl, 5-6 membered heteroaryloxy-C1-3-alkyl, phenyloxy-C1-3-alkyl, hydroxy-C1-3-alkyl, phenyl-C1-3-alkoxy-C1-3-alkyl, C1-6-alkylcarbonyl, C1-3-alkoxycarbonyl, C1-3-alkoxy-C1-3-alkylcarbonyl, C1-3-alkylaminocarbonyl, C3-6-cycloalkylcarbonyl, C3-6-cycloalkyl-C1-3-alkylcarbonyl, phenylcarbonyl, phenyl-C1-3-alkylcarbonyl, 5- or 6-membered heteroaryl-C1-3-alkylcarbonyl, 5- or 6-membered heteroarylcarbonyl and —
(CH2)n—
C3-5-cycloalkyl optionally substituted with C1-2-alkoxycarbonyl;
wherein R20 is selected from H, C1-7-alkyl, —
(CH2)n—
C5-6-cycloalkyl, —
(CH2)n-5-6-membered heterocyclyl, C1-3-alkylsulfonyl, amino-C1-3-alkyl and —
(CH2)n-phenyl;
alternatively R19 and R20 together with the nitrogen atom form a 5-6 membered heterocyclyl ring;
wherein R21 is selected from H, C1-3-alkyl, C2-3-alkenyl, C1-3-alkylthio-C1-3-alkyl, C1-3-alkylcarbonylamino-C1-3-alkyl, amino-C1-3-alkyl, —
(CH2)n-[5- or 6-membered heterocyclyl], —
(CH2)n—
C5-6-cycloalkyl, and —
(CH2)n-phenyl;
wherein R22 is selected from H, C1-3-alkyl, —
(CH2)n—
C4-6-cycloalkyl, —
(CH2)n-[5- or 6-membered heterocyclyl] and —
(CH2)n-phenyl;
alternatively R21 and R22 together with the amide nitrogen atom form a 5-6 membered heterocyclyl ring;
wherein R23 is selected from H, C1-3-alkyl, —
(CH2)n—
C4-6-cycloalkyl, —
(CH2)n-[5- or 6-membered heterocyclyl] and —
(CH2)n-phenyl;
wherein phenyl and heterocyclyl are optionally substituted with one or more substituents selected from C1-2-haloalkyl, C1-2-alkyl, —
(CH2)n—
C4-6-cycloalkyl, chloro, fluoro, —
OR17, —
NR17SO2R17, —
NR17CO2R17, —
N(R17)2, cyano, —
COR17, —
C(R17)2N(R17)2, nitro, —
SO2N(R17)2, —
S(O)mR17, and C1-2-haloalkoxy;
and pharmaceutically-acceptable salts thereof.
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22. Compound of claim 21 wherein R12 is selected from oxazolylpyridyl, 4-(N,N-dimethylamino)phenylmethyl, 2,2-dimethyl-oxazolidinyl and
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21. Compound of claim 20 wherein R10 is H;
Specification
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Current AssigneeAmgen Inc.
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Original AssigneeAmgen Inc.
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InventorsNorman, Mark H., Chen, Ning, Xi, Ning, Xu, Shimin, Kelly, Michael G., Liu, Qingyian, Han, Nianhe, Fotsch, Christopher H., Bo, Yunxin, Arasasingham, Premilla, Hsieh, Feng-Yin, Stec, Markian, Tamayo, Nuria, Goldberg, Martin H., Smith, Duncan M.
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Granted Patent
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Time in Patent OfficeDays
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Field of Search
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US Class Current514/218
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CPC Class CodesA61K 38/00 Medicinal preparations cont...A61P 3/04 Anorexiants; Antiobesity ag...A61P 3/10 for hyperglycaemia, e.g. an...A61P 43/00 Drugs for specific purposes...C07D 205/04 having no double bonds betw...C07D 207/08 with hydrocarbon radicals, ...C07D 207/09 Radicals substituted by nit...C07D 209/14 Radicals substituted by nit...C07D 209/42 Carbon atoms having three b...C07D 211/26 with hydrocarbon radicals, ...C07D 211/60 Carbon atoms having three b...C07D 211/62 attached in position 4C07D 213/38 having only hydrogen or hyd...C07D 213/81 Amides; ImidesC07D 213/82 in position 3C07D 215/48 Carbon atoms having three b...C07D 217/06 with the ring nitrogen atom...C07D 217/14 other than aralkyl radicalsC07D 217/26 Carbon atoms having three b...C07D 233/64 with substituted hydrocarbo...C07D 295/185 : from aliphatic carboxylic a...C07D 317/60 : Radicals substituted by car...C07D 317/68 : Carbon atoms having three b...C07D 319/18 : Ethylenedioxybenzenes, not ...C07D 401/12 : linked by a chain containin...C07D 403/12 : linked by a chain containin...C07D 409/12 : linked by a chain containin...C07D 413/12 : linked by a chain containin...C07D 417/12 : linked by a chain containin...C07D 451/02 : containing not further cond...C07K 5/06026 : the side chain containing 0...C07K 5/06139 : with the first amino acid b...C07K 5/06147 : and His-amino acid; Derivat...C07K 5/06191 : containing heteroatoms diff...