US 12,479,797 B2Granted

Cyclopropyl-amide compounds as dual LSD1/HDAC inhibitors

AssigneeJubilant Epicore LLC

InventorsSridharan Rajagopal, Mahanandeesha S. Hallur, Purushottam Dewang, Kannan Murugan, Durga Prasanna Kumar C.H., Pravin Iyer, Chandrika Mulakala, Dhanalakshmi Sivanandhan, Sreekala Nair, Mohd Zainuddin, Subramanyam Janardhan Tantry, Chandru Gajendran, Sriram Rajagopal

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Abstract

The present disclosure describes novel compounds of the general Formula (I), their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds can inhibit both LSD and HDAC and are useful as therapeutic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer's disease, parkinson's disease and the like.

Claims6

Dependent claims

A method of inhibiting both LSD1 and HDAC6 in a cell, the method comprising treating the cell with an effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof;
wherein,
Ar is selected from the group consisting of substituted or unsubstituted C5-6aryl, C1-6heteroaryl, and C2-10heterocyclyl with heteroatoms selected from N, O or S;
W represents a bond or CR4R5,
wherein R4 and R5 are independently selected from the group consisting of hydrogen, and substituted or unsubstituted C1-8alkyl;
Y is selected from the group consisting of substituted or unsubstituted C1-8alkyl, C2-8alkenyl, C5-6aryl, C1-6heteroaryl, C2-10heterocyclyl, C3-8cycloalkyl, CO—, and —CO—C2-10heterocyclyl,
wherein C1-8alkyl, C5-6aryl, C1-6heteroaryl, C2-10heterocyclyl, and C3-8cycloalkyl is optionally substituted with one or more of the groups selected from hydrogen, C1-6 alkyl, and oxo (═O);
Z represents a bond or is selected from the group consisting of C1-8alkyl, C2-8alkenyl, C6-12-alkylaryl, C7-15-arylalkenyl, C2-12-alkylheteroaryl, —CO—C7-12alkylaryl, —CO—C7-12alkenylaryl, —CONR6—C1-8 alkyl, CONR6—C5-6aryl-, C5-6aryl, C1-6heteroaryl, C2-10 heterocyclyl, —CO—C2-10 heterocyclyl, —NR6CO—C5-6aryl-, —NR6—C5-6aryl, NR6—C1-6heteroaryl, —C1-8alkyl-O—C5-6aryl, —O—C5-6aryl, O—C1-6heteroaryl, —CONR6—C7-12alkylaryl, —SO2—C5-6aryl, —SO2—C7-12alkylaryl, —NR6SO2—C7-12alkyl aryl, C1-8 alkyl-CONR6—C5-6aryl, and OCONR6—C5-6aryl;
R6 is selected from the group consisting of hydrogen, and C1-8 alkyl;
R1 is selected from the group consisting of hydrogen, halogen, oxo (═O), C1-8alkyl, C1-8haloalkyl, C1-8alkoxy, C3-8cycloalkyl, C5-6aryl, C2-10heterocyclyl, C1-6heteroaryl, —C(O)Rb, —C(O)NRaRb, and —ORa;
wherein Ra and Rb is independently selected from the group consisting of hydrogen, C1-8alkyl, C5-6aryl, C7-15arylalkyl and C2-10heterocyclyl with heteroatoms selected from N, O or S;
and
wherein C1-8alkyl, C5-6aryl, C1-6heteroaryl, C2-10heterocyclyl, and C3-8cycloalkyl, is optionally substituted with one or more of the groups selected from hydrogen, C1-6 alkyl, oxo (═O), halogen, and cyano;
R3 is selected from the group consisting of hydrogen, and substituted or unsubstituted C1-8alkyl;
R2 is selected from the group consisting of —OR7 and aniline,
wherein, aniline is optionally substituted with one or more halogen;
and
R7 is hydrogen.

15 more elements

A method of inhibiting both LSD1 and HDAC6 in a cell, the method comprising treating the cell with an effective amount of a compound or pharmaceutical salt thereof, wherein the compound or pharmaceutical salt thereof, is selected from the group consisting of:

1) (E)-3 (4 (((2 (4cyclopropylphenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide TFA salt;
2) (E)-3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-phenyl)-N-hydroxy-acrylamide TFA salt;
3) (E)-3-(4-(((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide TFA salt;
4) (E)-N-hydroxy-3-(4-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)phenyl) acrylamide TFA salt;
5) (E)-3-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide TFA salt;
6) (E)-3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide TFA salt;
7) (E)-N-hydroxy-3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)phenyl)acrylamide TFA salt;
8) 2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxy pyrimidine-5-carboxamide TFA salt;
9) 2-[4-(2-Phenyl-cyclopropylamino)-piperidin-1-yl]-pyrimidine-5-carboxylicacid hydroxyamide TFA salt;
10) 2-{4-[2-(4-Fluoro-phenyl)-cyclopropylamino]-piperidin-1-yl}-pyrimidine-5-carboxylic acid hydroxyamide TFA salt;
11) 2-(4-(((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
12) 2-(4-((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
13) 2-(4-((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
14) 2-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
15) 2-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
16) 2-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
17) N-hydroxy-2-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide TFA salt;
18) N-hydroxy-2-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide TFA salt;
19) N-hydroxy-2-(4-((2-(4-methoxyphenyl)cyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxamide TFA salt;
20) 2-(4-((((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
21) 2-(4-((((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
22) 4-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxybenzamide TFA salt;
23) N-hydroxy-2-(2-(((2-phenylcyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7 (8H)-yl)pyrimidine-5-carboxamide TFA salt;
24) N-hydroxy-2-(2-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a] pyrazin-7 (8H)-yl)pyrimidine-5-carboxamide TFA salt;
25) 2-(2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7 (8H)-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt;
26) 3-(((2-(4-bromophenyl)cyclopropyl)amino)methyl)-N-hydroxybenzamide TFA salt;
27) N-hydroxy-3-(((2-phenylcyclopropyl)amino)methyl)benzamide TFA salt;
28) N-hydroxy-4-(((2-phenylcyclopropyl)amino)methyl)benzamide TFA salt;
29) N-hydroxy-6-((2-phenylcyclopropyl)amino)hexanamide TFA salt;
30) 4-(3-((2-(4-fluorophenyl)cyclopropyl)amino)propyl)-N-hydroxybenzamide TFA salt;
31) N-(6-Hydroxycarbamoyl-hexyl)-4-[(2-phenyl-cyclopropylamino)-methyl]-benzamide TFA salt;
32) 4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide TFA salt;
33) 4-(2-Phenyl-cyclopropylamino)-cyclohexanecarboxylic acid hydroxyamide TFA salt;
34) (1S,4R)—N-hydroxy-4-((1S)-1-((2phenylcyclopropyl)amino)ethyl)cyclohexanecarboxamide TFA salt;
35) N-hydroxy-4-((4-(((2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt;
36) N-Hydroxy-4-{4-[(2-phenyl-cyclopropylamino)-methyl]-piperidin-1-ylmethyl}-benzamide TFA salt;
37) 4-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)-N-hydroxybenzamide TFA salt;
38) N-hydroxy-4-((4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt;
39) 6-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)-N-hydroxynicotinamide TFA salt;
40) N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)benzamide TFA salt;
41) N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzamide TFA salt;
42) N-hydroxy-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide TFA salt;
43) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
44) N-hydroxy-4-(3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamide TFA salt;
45) N-hydroxy-4-(3-(4-((methyl (2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) propyl)benzamide TFA salt;
46) N-hydroxy-4-(3-(6-((2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-1)propyl)benzamide TFA salt;
47) 4-[3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-piperidin-1-yl)-propyl]-N-hydroxy-benzamide TFA salt;
48) 4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxy benzamide TFA salt;
49) 4-(3-(4-(((2-(3-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxy benzamide TFA salt;
50) 4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt;
51) N-hydroxy-4-(3-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
52) N-hydroxy-4-(3-(4-(((2-(4-(morpholine-4-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
53) N-hydroxy-4-(3-(4-(((2-(4-(morpholine-4-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
54) N-hydroxy-4-(3-(4-(((2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
55) N-(2-(dimethylamino)ethyl)-4-(2-(((1-(3-(4-(hydroxycarbamoyl)phenyl)propyl)piperidin-4-yl)methyl)amino)cyclopropyl)benzamide TFA salt;
56) 4-(3-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt;
57) 4-(3-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt;
58) 4-(3-(3-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)azetidin-1-yl) propyl)-N-hydroxybenzamide;
59) 4-(3-(4-(((2-(4′-cyano-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt;
60) N-hydroxy-4-(3-(4-(((2-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
61) N-hydroxy-4-(3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
62) N-hydroxy-4-(3-(4-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
63) N-hydroxy-4-(3-(3-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)benzamide;
64) 4-(3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt;
65) 3-(3-(3-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxybenzamide TFA salt;
66) N-hydroxy-4-(3-(4-(((2-(4-(6-(trifluoromethyl) pyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
67) N-hydroxy-4-(3-(4-(((2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
68) N-hydroxy-4-(3-(4-(((2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
69) N-hydroxy-4-(3-(4-(((2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
70) N-hydroxy-4-(3-(4-(((2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
71) N-hydroxy-4-(3-(2-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7 (8H)-yl)propyl)benzamide TFA salt;
72) 4-(3-(2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)-N-hydroxybenzamide TFA salt;
73) 4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl) propyl)-N-hydroxybenzamide TFA salt;
74) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide TFA salt;
75) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide;
76) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)benzamide TFA salt;
77) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzamide TFA salt;
78) 4-(3-(6-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2-(1H)-yl)propyl)-N-hydroxybenzamide TFA salt;
79) 4-((7-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2 (1H)-yl)methyl)-N-hydroxybenzamide TFA salt;
80) 4-((2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7 (8H)-yl)methyl)-N-hydroxybenzamide TFA salt;
81) N-hydroxy-4-(3-(4 (((2-(1,3,3,-trimethyl-2-oxoindoline-5-yl)cyclopropyl)amino)methyl)piperidine-1-yl)propyl)benzamide TFA salt;
82) N-hydroxy-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
83) N-hydroxy-4-(3-oxo-3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamide TFA salt;
84) N-hydroxy-4-(2-oxo-2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide TFA salt;
84A. N-hydroxy-4-(2-oxo-2-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide;
84B. N-hydroxy-4-(2-oxo-2-(4-((((1S,2R)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide;
85) N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)benzamide TFA salt;
86) N-hydroxy-4-((N-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl) sulfamoyl)methyl)benzamide TFA salt;
87) 4-(N-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl) sulfamoyl)-N-hydroxybenzamide;
88) N-hydroxy-4-(2-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl)benzamide TFA salt;
89) N-hydroxy-N4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl) terephthalamide TFA salt;
90) N1-(2-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)-N4-hydroxyterephthalamide TFA salt;
91) N-hydroxy-4-((4-(2-((2-phenylcyclopropyl)amino)acetyl) piperazin-1-yl)methyl)benzamide TFA salt;
92) N-hydroxy-4-(3-oxo-3-(4-(2-((2-phenylcyclopropyl)amino)acetyl)piperazin-1-yl)propyl)benzamide TFA salt;
93) N-hydroxy-4-(3-(1-(2-((2-phenylcyclopropyl)amino) acetyl)piperidin-4-yl)propyl)benzamide TFA salt;
94) N-hydroxy-4-(3-(2-oxo-4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) propyl)benzamide TFA salt;
95) N-hydroxy-4-(2-((2-phenylcyclopropyl)amino)ethoxy)benzamide TFA salt;
96) 6-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)-N-hydroxynicotinamide TFA salt;
97) N-hydroxy-6-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinamide TFA salt;
98) 6-(2-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl) ethoxy)-N-hydroxynicotinamide TFA salt;
99) N-hydroxy-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)benzamide TFA salt;
100) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propoxy)benzamide TFA salt;
101) N-hydroxy-4-(3-((2-phenylcyclopropyl)amino)propoxy)benzamide TFA salt;
102) 2-((2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)amino)-N-hydroxypyrimidine-5-carboxamide TFA salt;
103) 5-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydro thieno[3,2-c]pyridine-2-carboxamide TFA salt;
103A) 5-(2-(((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide;
103B) 5-(2-(((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide;
104) 2-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydro isoquinoline-7-carboxamide TFA salt;
104A) 2-(2-(((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;
104B) 2-(2-(((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;
105) 5-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxy-4,5,6,7-tetrahydro thieno[3,2-c]pyridine-2-carboxamide TFA salt;
106) 5-(4-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)butanoyl)-N-hydroxy-4,5,6, 7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide TFA salt;
107) 2-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxy-1,2,3,4-tetrahydro isoquinoline-7-carboxamide TFA salt;
108) 2-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxyisoindoline-5-carboxamide TFA salt;
109) N-hydroxy-2-(4-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)butanoyl) isoindoline-5-carboxamide TFA salt;
110) N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl) thiazole-4-carboxamide TFA salt;
111) 2-(3-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxythiazole-4-carboxamide;
112) N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl) thiazole-5-carboxamide TFA salt;
113) N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl) oxazole-4-carboxamide;
114) (E)-N-hydroxy-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) prop-1-en-1-yl)benzamide TFA salt;
114A)N-hydroxy-4-((E)-3-oxo-3-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl) piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt;
114B)N-hydroxy-4-((E)-3-oxo-3-(4-((((1S,2R)-2-phenylcyclopropyl)amino)methyl) piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt;
115) 4-((E)-3-(4-((((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt;
115A) 4-((E)-3-(4-((((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt;
116) (E)-4-(3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl) piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt;
117) (E)-N-hydroxy-4-(3-oxo-3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt;
118) (E)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt;
119) (E)-N-hydroxy-4-(3-(3-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide TFA salt;
120) (E)-N-(2-aminophenyl)-3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)phenyl)acrylamide TFA salt;
121) N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
122) N-(2-aminophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
123) N-(2-aminophenyl)-4-(3-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
124) N-(2-aminophenyl)-4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl) piperidin-1-yl)propyl)benzamide TFA salt;
125) N-(2-aminophenyl)-4-(3-(4-(((2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
126) N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)benzamide TFA salt;
127) N-(2-aminophenyl)-4-(3-(6-((2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-yl)propyl)benzamide TFA salt;
128) N-(2-aminophenyl)-4-(3-(4-(((2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
129) N-(2-aminophenyl)-4-(3-(4-(((2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
130) N-(2-aminophenyl)-4-(3-(4-(((2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl) piperidin-1-yl)propyl)benzamide TFA salt;
131) N-(2-aminophenyl)-4-(3-(4-(((2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
132) N-(2-amino-5-fluorophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
133) N-(2-aminophenyl)-4-(3-oxo-3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamide TFA salt;
134) N-(2-aminophenyl)-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt;
135) N-(2-aminophenyl)-4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide TFA salt;
136) N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide;
137) N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzamide TFA salt;
138) N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)benzamide TFA salt;
139) N-(2-aminophenyl)-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide TFA salt;
140) N-(2-aminophenyl)-4-((4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt;
141) N-(2-aminophenyl)-4-((4-(((2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt;
142) N-(2-aminophenyl)-4-((4-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt;
143) N-(2-aminophenyl)-4-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt;
144) N-(2-aminophenyl)-4-((4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt;
145) N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)benzamide TFA salt;
146) N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzamide TFA salt;
147) N-(2-aminophenyl)-4-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-2-oxoethyl)benzamide TFA salt;
148) N-(2-aminophenyl)-4-(2-((2-(4-fluorophenyl)cyclopropyl)amino) ethoxy)benzamide TFA salt;
149) N-(2-aminophenyl)-6-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinamide TFA salt;
150) N-(−2-aminophenyl)-2-((2-4 (((2-(4-flurophenyl)cyclopropyl)amino)methyl)piperdine-1-yl)ethyl)amino)pyrimidine-5-carboxamide TFA salt;
151) N-(2-aminophenyl)-5-((2-(4-fluorophenyl)cyclopropyl)glycyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide TFA salt;
152) N-(2-aminophenyl)-2-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide TFA salt;
153) N-(2-aminophenyl)-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl) oxazole-4-carboxamide TFA salt;
154) N-(2-aminophenyl)-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)thiazole-5-carboxamide TFA salt;
155) N-(2-aminophenyl)-4-((2-((2-(4-fluorophenyl)cyclopropyl)amino)acetamido)methyl)benzamide TFA salt;
156) (E)-N-(2-aminophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide TFA salt;
157) (E)-N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide TFA salt;
158) N-(4-((2-aminophenyl)carbamoyl)benzyl)-4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxamide TFA salt;
159) N-(2-aminophenyl)-4-(3-(2-oxo-4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide;
160) N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)benzamide TFA salt;
161) N-(2-aminophenyl)-4-(((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)methyl)benzamide TFA salt;
and
162) N-(2-aminophenyl)-4-(2-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl)benzamide TFA salt.

169 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/733,736Filed 29 Apr 2022 · division
Priority: IN 2016410161299 May 2016
Published: US 2022/0281815 A18 Sep 2022
Granted: 25 Nov 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification36 codes

C07D 205/12
Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom: condensed with carbocyclic rings or…
C07D 261/08
Having two or more double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00

Family

PCT/IN2017/050167Parent of this division · filed 8 May 2017
US 2022/0281815 A1Pre-grant publication · published 8 Sep 2022
Application16/098,341Parent of this division
US 11,352,322 B2Parent of this division
US 2020/0308110 A1Published application
US 12,479,797 B2This patent

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