US 12,162,848 B2Granted

Inhibitors of protein tyrosine phosphatase, compositions, and methods of use

AssigneeBristol-Myers Squibb Company

InventorsHaibo Liu, Laura Akullian D'Agostino, Shoshana L. Posy, Annapurna Pendri, Swanee E. Jacutin-Porte

Life of this patent

Estimating the term…

Abstract

Disclosed are compounds of Formula (I) pharmaceutically acceptable salts thereof are defined herein, and pharmaceutical compositions thereof and combinations thereof, and methods of using the same as inhibitors of protein tyrosine phosphatases (PTPN2). These compounds are useful in treating cancer and diseases susceptible to PNPT2 inhibition.

Claims17

Dependent claims

A compound of Formula (I):

wherein:
R1 is selected from the group consisting of:
—CONHR3, —CH2N(R5)CH2R4, 4-aminopiperidin-1-yl,
R2 is selected from the group consisting of —H,
R3 is selected from the group consisting of -heteroalicyclyl and —CH2CH2N(CH3)2;
R4 is selected from the group consisting of -alkyl, -heteroaryl, -carboalicyclyl, and 1-methyl-1H-pyrazol-4-yl;
R5 is selected from the group consisting of -alkyl and -carboalicyclyl;
R6 is selected from the group consisting of —H and -alkyl;
R7 is selected from the group consisting of and N;
R8 is selected from the group consisting of —NH—, —CH2CH2NHCH2—,
R9 is selected from the group consisting of —CH2—, —NH—, —O—, —CH(R31)—, and —N(R32)—;
R10 is selected from the group consisting of —H, -alkyl, —N(CH3)2, and —CH2CH2OCH3;
R11 is selected from the group consisting of —CH═, —N═, and —C(R33)═;
R12 is selected from the group consisting of —CH═, —N═, and —C(R34)═;
R13 is selected from the group consisting of —CH═ and —N═;
R14 is selected from the group consisting of —H, -alkyl, phenoxy, and
R15 is selected from the group consisting of —NH—, —O—, and —N(R35)—;
R16 is selected from the group consisting of —H, —OH, —OCH3, and —N(CH3)2;
R17 is selected from the group consisting of —H and —OCH3;
R18 is selected from the group consisting of —CH═, —N═, and
R19 is selected from the group consisting of —CH═, —N═, and —CCH3═;
R20 is selected from the group consisting of —H and —CN;
R21 is selected from the group consisting of —H, -alkyl, and -halogen;
R22 is selected from the group consisting of —NHCH2—, —CH2N(R6)CH2—, and
R23 is selected from the group consisting of —CH═, —N═, and —C(R36)═;
R24 is selected from the group consisting of —H, -alkyl, -halogen, and —CN;
R25 is selected from the group consisting of —H and -halogen;
R26 is selected from the group consisting of —CH2—, —NH—, —O—, —CH(R37)—, —C(CH3)2—, and
R27 is selected from the group consisting of —CH2— and —CO—;
R28 is selected from the group consisting of —H, -alkyl, and -carboalicyclyl;
R29 is selected from the group consisting of —O—, —CH(R38)—, and —N(R39)—;
R30 is selected from the group consisting of —CH2—, —O—, and —C(CH3)2—;
R31 is selected from the group consisting of —OH, -halogen, -carboaryl, —OCH3, —N(CH3)2, —CH2N(CH3)2, —OCH(CH3)2, and —CH2CH2R40CH3;
R32 is selected from the group consisting of -alkyl, —CCH3O, —CH2CH2OCH3, —CH2CONHCH3, and —R27CH2CH(CH3)2;
R33 is selected from the group consisting of -halogen, —OCH3, and cyclopropylmethoxy;
R34 is selected from the group consisting of -alkyl, -halogen, —OCH2CH3, —C(CH3)2R41, —CH2NHCCH3O, (pyrrolidin-1-yl)methyl, benzyl,
R35 is selected from the group consisting of —CCH3O, —R27CH2R42, and —SO2R43;
R36 is selected from the group consisting of -halogen and —CN;
R37 is selected from the group consisting of —NH2, —N(CH3)2, —CONHCH3, and —NHCCH3O;
R38 is selected from the group consisting of -halogen and —N(CH3)2;
R39 is -alkyl;
R40 is selected from the group consisting of —CH2— and —O—;
R41 is selected from the group consisting of —OH, -alkyl, and —CN;
R42 is selected from the group consisting of -alkyl and —COOH;
R43 is selected from the group consisting of -alkyl, -carboalicyclyl, and 3-fluorophenyl.

42 more elements

A compound selected from the group consisting of:

Compound
number
Structure
Chemical name
EXAMPLE 1
5-(2-fluoro-6- hydroxy-4-(piperidin- 3-yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 2
-[2-fluoro-6-hydroxy- 4-(4- piperidyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 3
5-(2-fluoro-6- hydroxy-4-(1- methylpiperidin-3- yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 4
5-[2-fluoro-6- hydroxy-4-(1-methyl- 4-piperidyl)phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 5
5-(2-fluoro-6- hydroxy-4-(1- isopentylpiperidin-3- yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 6
5-[2-fluoro-6- hydroxy-4-(1- isopentyl-4- piperidyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 7
5-(2-fluoro-6- hydroxy-4-(pyridin-2- yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 8
5-(2-fluoro-6- hydroxy-4-(pyridin-3- yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 9
5-(2-fluoro-6- hydroxy-4-(pyridin-4- yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 10
5-[4-(4- benzylphenyl)-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 11
5-[2-fluoro-6- hydroxy-4-(3- phenylphenyl)phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 12
5-[2-fluoro-4-[4-(4- fluorophenyl)phenyl]- 6-hydroxy-phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 13
5-[2-fluoro-6- hydroxy-4-(4- morpholinophenyl)ph enyl]-1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 14
5-[2-fluoro-6- hydroxy-4-(3- phenoxyphenyl)pheny 1]-1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 15
5-[2-fluoro-6- hydroxy-4-(4- isobutylphenyl)phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 16
5-[2-fluoro-6- hydroxy-4-(3- morpholinophenyl)ph enyl]-1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 17
5-[4-(4- cyclopropylphenyl)-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 18
5-[2-fluoro-6- hydroxy-4-(4-phenyl- 2-thienyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 19
5-[2-fluoro-6- hydroxy-4-[4- (pyrrolidin-1- ylmethyl)phenyl]phen yl]-1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 20
5-[2-fluoro-6- hydroxy-4-(2-phenyl- 4-pyridyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 21
5-[4-[3- (cyclopropylmethoxy)- 5-methyl-phenyl]-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 22
5-[2-fluoro-6- hydroxy-4-[4-(1- hydroxy-1-methyl- ethyl)phenyl]phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 23
5-[2-fluoro-6- hydroxy-4-(6- methoxy-3- pyridyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 24
5-[2-fluoro-6- hydroxy-4-(3- quinolyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 25
5-[2-fluoro-6- hydroxy-4-(2- methoxy-3- pyridyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 26
5-[2-fluoro-6- hydroxy-4-(6- hydroxy-3- pyridyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 27
5-[2-fluoro-6- hydroxy-4-[6-(4- methylpiperazin-1-yl)- 3-pyridyl]phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 28
5-[2-fluoro-6- hydroxy-4-(5- methoxy-3- pyridyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 29
5-[4-[6- (dimethylamino)-3- pyridyl]-2-fluoro-6- hydroxy-phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 30
5-[2-fluoro-6- hydroxy-4-(6-phenyl- 3-pyridyl)phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 31
5-(2-fluoro-6- hydroxy-4-((4- methylpiperazin-1- yl)methyl)phenyl)- 1,2,5-thiadiazolidin-3- one 1,1-dioxide
EXAMPLE 32
5-(2-fluoro-6- hydroxy-4-((4- isopentylpiperazin-1- yl)methyl)phenyl)- 1,2,5-thiadiazolidin-3- one 1,1-dioxide
EXAMPLE 33
5-(4-((4- (dimethylamino)piperidin- 1-yl)methyl)-2- fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 34
5-[4- [(cyclohexylamino) methyl]-2-fluoro-6- hydroxy-phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 35
5-[2-fluoro-6- hydroxy-4- [(tetrahydropyran-4- ylamino)methyl]phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 36
5-(2-fluoro-6- hydroxy-4-((4-(3- methylbutanoyl) piperazin-1- yl)methyl)phenyl)- 1,2,5-thiadiazolidin-3- one 1,1-dioxide
EXAMPLE 37
5-(4-(((4,4- dimethylcyclohexyl) amino)methyl)-2- fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 38
5-(4-((4- acetylpiperazin-1- yl)methyl)-2-fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 39
5-(2-fluoro-6- hydroxy-4-((piperidin- 4- ylamino)methyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 40
5-(4-(((1- ethylpiperidin-4- yl)amino)methyl)-2- fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 41
5-(2-fluoro-6- hydroxy-4- (morpholinomethyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 42
5-(2-fluoro-4-((4- fluoropiperidin-1- yl)methyl)-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 43
5-(4- ((cyclohexyl(methyl) amino)methyl)-2- fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 44
5-(2-fluoro-6- hydroxy-4-((4-(2- methoxyethyl) piperazin-1- yl)methyl)phenyl)- 1,2,5-thiadiazolidin-3- one 1,1-dioxide
EXAMPLE 45
2-fluoro-5-[[3-fluoro- 5-hydroxy-4-(1,1,4- trioxo-1,2,5- thiadiazolidin-2- yl)phenyl]methylamino] methyl]benzonitrile
EXAMPLE 46
5-[2-fluoro-6- hydroxy-4-[[2-(1- methyl-4- piperidyl)ethylamino] methyl]phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 47
5-[2-fluoro-6- hydroxy-4-[(4-phenyl- 1- piperidyl)methyl] phenyl]-1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 48
5-[4- [[cyclopropyl(propyl) amino]methyl]-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 49
5-[4- [[cyclobutylmethyl (methyl)amino]methyl]- 2-fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 50
3-[[[3-fluoro-5- hydroxy-4-(1,1,4- trioxo-1,2,5- thiadiazolidin-2- yl)phenyl]methyl- methyl- amino]methyl] benzonitrile
EXAMPLE 51
5-[4-[[(1R)-3,3- dimethylcyclohexyl] amino]methyl]-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 52
5-[2-fluoro-6- hydroxy-4-[(4- hydroxy-1- piperidyl)methyl]phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 53
5-[2-fluoro-6- hydroxy-4-[(4- methoxy-1- piperidyl)methyl] phenyl]-1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 54
5-[2-fluoro-6- hydroxy-4-[(4- isopropoxy-1- piperidyl)methyl]phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 55
5-[2-fluoro-6- hydroxy-4-[[4-(2- methoxyethyl)-1- piperidyl]methyl] phenyl]-1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 56
5-[4-[[4- [(dimethylamino) methyl]-1- piperidyl]methyl]-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 57
5-[4-[(4-butyl-1- piperidyl)methyl]-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 58
(1r,4r)-4-((4-(1,1- dioxido-4-oxo-1,2,5- thiadiazolidin-2-yl)-3- fluoro-5- hydroxybenzyl) amino)-N- methylcyclohexane-1- carboxamide
EXAMPLE 59
2-(4-(4-(1,1-dioxido- 4-oxo-1,2,5- thiadiazolidin-2-yl)-3- fluoro-5- hydroxybenzyl) piperazin-1-yl)-N- methylacetamide
EXAMPLE 60
N-((1r,4r)-4-((4-(1,1- dioxido-4-oxo-1,2,5- thiadiazolidin-2-yl)-3- fluoro-5- hydroxybenzyl)amino) cyclohexyl)acetamide
EXAMPLE 61
(R)-5-(2-fluoro-6- hydroxy-4-((piperidin- 3- ylamino)methyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 62
(R)-5-(2-fluoro-6- hydroxy-4-(((1- isopentylpiperidin-3- yl)amino)methyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 63
5-[2-fluoro-6- hydroxy-4-[[[(3S)-1- isopentyl-3- piperidyl]amino]methyl] phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 64
(R)-5-(2-fluoro-6- hydroxy-4- (((tetrahydro-2H- pyran-3- yl)amino)methyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 65
(S)-5-(2-fluoro-6- hydroxy-4-((piperidin- 3- ylamino)methyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 66
(S)-5-(4-(((3,3- dimethylcyclohexyl) amino)methyl)-2- fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 67
(S)-5-(2-fluoro-6- hydroxy-4- (((tetrahydro-2H- pyran-3- yl)amino)methyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 68
5-[4-[[[(3R)-1-acetyl- 3- piperidyl]amino] methyl]-2-fluoro-6- hydroxy-phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 69
5-[2-fluoro-4-[[[(3R)- 1-(3- fluorophenyl)sulfonyl- 3- piperidyl]amino] methyl]-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 70
5-[2-fluoro-4-[[(3S)- 1-(3- fluorophenyl)sulfonyl- 3- piperidyl]amino] methyl]-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 71
5-[4-[[[(3S)-1-acetyl- 3- piperidyl]amino] methyl]-2-fluoro-6- hydroxy-phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 72
5-[2-fluoro-6- hydroxy-4-[[[(3R)-1- methylsulfonyl-3- piperidyl]amino]meth yl]phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 73
5-[4-[[[(3S)-1- cyclopropylsulfonyl- 3- piperidyl]amino] methyl]-2-fluoro-6- hydroxy-phenyl]-1,1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 74
5-[4-[[[(3R)-1- cyclopropylsulfonyl- 3- piperidyl]amino] methyl]-2-fluoro-6- hydroxy-phenyl]-1, 1- dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 75
5-[2-fluoro-6- hydroxy-4-[[[(3S)-1- methylsulfonyl-3- piperidyl]amino] methyl]phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 76
3-[(3S)-3-[[3-fluoro- 5-hydroxy-4-(1,1,4- trioxo-1,2,5- thiadiazolidin-2-yl) phenyl] methylamino]-1- piperidyl]-3-oxo- propanoic acid
EXAMPLE 77
5-[4-[[(4,4- dimethylcyclohexyl)- methyl- amino]methyl]-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 78
5-[4- [cyclobutylmethyl (propyl)amino]methyl]- 2-fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 79
5-[[3-fluoro-5- hydroxy-4-(1,1,4- trioxo-1,2,5- thiadiazolidin-2- yl)phenyl]methylamino] pyridine-3- carbonitrile
EXAMPLE 80
5-[4-[(2-chloro-5- fluoro- anilino)methyl]-2- fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 81
4-chloro-3-[[3-fluoro- 5-hydroxy-4-(1,1,4- trioxo-1,2,5- thiadiazolidin-2-yl) phenyl] methylamino]benzonitrile
EXAMPLE 82
5-[4-[[(4-cyclopropyl- 2- pyridyl)amino]methyl]- 2-fluoro-6-hydroxy- phenyl]-1,1-dioxo- 1,2,5-thiadiazolidin-3- one
EXAMPLE 83
5-(2-fluoro-6- hydroxy-4-(4- isopentylpiperazin-1- yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 84
5-(4-(4- aminopiperidin-1-yl)- 2-fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 85
5-(2-fluoro-6- hydroxy-4-(piperazin- 1-yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 86
5-(2-fluoro-6- hydroxy-4-(4-(2- methoxyethyl)piperazin- 1-yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 87
5-(4-(4- (dimethylamino)piperidin- 1-yl)-2-fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 88
5-(2-fluoro-6- hydroxy-4-(piperidin- 4-ylamino)phenyl)- 1,2,5-thiadiazolidin-3- one 1,1-dioxide
EXAMPLE 89
5-(2-fluoro-6- hydroxy-4-((1- isopentylpiperidin-4- yl)amino)phenyl)- 1,2,5-thiadiazolidin-3- one 1,1-dioxide
EXAMPLE 90
5-(2-fluoro-6- hydroxy-4-((1-(2- methoxyethyl)piperidin- 4-yl)amino)phenyl)- 1,2,5-thiadiazolidin-3- one 1,1-dioxide
EXAMPLE 91
N-(2- (dimethylamino)ethyl)- 4-(1,1-dioxido-4-oxo- 1,2,5-thiadiazolidin-2- yl)-3-fluoro-5- hydroxybenzamide
EXAMPLE 92
4-(1, 1-dioxido-4-oxo- 1,2,5-thiadiazolidin-2- yl)-3-fluoro-5- hydroxy-N-(piperidin- 4-yl)benzamide
EXAMPLE 93
(S)-4-(1,1-dioxido-4- oxo-1,2,5- thiadiazolidin-2-yl)-3- fluoro-5-hydroxy-N- (piperidin-3- yl)benzamide
EXAMPLE 94
(R)-4-(1,1-dioxido-4- oxo-1,2,5- thiadiazolidin-2-yl)-3- fluoro-5-hydroxy-N- (piperidin-3- yl)benzamide
EXAMPLE 95
N-((1r,4r)-4- aminocyclohexyl)-4- (1,1-dioxido-4-oxo- 1,2,5-thiadiazolidin-2- yl)-3-fluoro-5- hydroxybenzamide
EXAMPLE 96
N-((1r,4r)-4- (dimethylamino) cyclohexyl)-4-(1,1-dioxido- 4-oxo-1,2,5- thiadiazolidin-2-yl)-3- fluoro-5- hydroxybenzamide
EXAMPLE 97
5-(3-(((4,4- dimethylcyclohexyl) amino)methyl)-2- fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 98
5-(2-fluoro-3-((4- fluoropiperidin-1- yl)methyl)-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 99
5-(2-fluoro-6- hydroxy-3- (morpholinomethyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 100
5-(3- ((cyclohexylamino) methyl)-2-fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 101
5-(2-fluoro-6- hydroxy-3- (((tetrahydro-2H- pyran-4- yl)amino)methyl) phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 102
5-(3-((4- (dimethylamino) piperidin-1-yl)methyl)- 2-fluoro-6- hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 103
5-(2-fluoro-6- hydroxy-3-((4- methylpiperazin-1- yl)methyl)phenyl)- 1,2,5-thiadiazolidin-3- one 1,1-dioxide
EXAMPLE 104
5-[2-fluoro-6- hydroxy-3-[(4- isopentylpiperazin-1- yl)methyl]phenyl]- 1,1-dioxo-1,2,5- thiadiazolidin-3-one
EXAMPLE 105
5-(2-fluoro-6- hydroxy-3-(piperidin- 4-yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
EXAMPLE 106
5-(2-fluoro-6- hydroxy-3-(1- methylpiperidin-4- yl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide
or pharmaceutically acceptable salts thereof.

214 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/161,184Filed 30 Jan 2023 · us provisional application
Priority: 31 Jan 2022
Published: US 2023/0322695 A112 Oct 2023
Granted: 10 Dec 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 285/06
Not condensed with other rings: 1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 35/00
Antineoplastic agents
C07D 285/10
Not condensed with other rings: 1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles

Family

Application63/305,022Us provisional application · filed 31 Jan 2022
US 2023/0322695 A1Pre-grant publication · published 12 Oct 2023
US 12,162,848 B2This patent

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

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Abstract

A compound of Formula (I):

wherein:
R1 is selected from the group consisting of:
—CONHR3, —CH2N(R5)CH2R4, 4-aminopiperidin-1-yl,
R2 is selected from the group consisting of —H,
R3 is selected from the group consisting of -heteroalicyclyl and —CH2CH2N(CH3)2;
R4 is selected from the group consisting of -alkyl, -heteroaryl, -carboalicyclyl, and 1-methyl-1H-pyrazol-4-yl;
R5 is selected from the group consisting of -alkyl and -carboalicyclyl;
R6 is selected from the group consisting of —H and -alkyl;
R7 is selected from the group consisting of and N;
R8 is selected from the group consisting of —NH—, —CH2CH2NHCH2—,
R9 is selected from the group consisting of —CH2—, —NH—, —O—, —CH(R31)—, and —N(R32)—;
R10 is selected from the group consisting of —H, -alkyl, —N(CH3)2, and —CH2CH2OCH3;
R11 is selected from the group consisting of —CH═, —N═, and —C(R33)═;
R12 is selected from the group consisting of —CH═, —N═, and —C(R34)═;
R13 is selected from the group consisting of —CH═ and —N═;
R14 is selected from the group consisting of —H, -alkyl, phenoxy, and
R15 is selected from the group consisting of —NH—, —O—, and —N(R35)—;
R16 is selected from the group consisting of —H, —OH, —OCH3, and —N(CH3)2;
R17 is selected from the group consisting of —H and —OCH3;
R18 is selected from the group consisting of —CH═, —N═, and
R19 is selected from the group consisting of —CH═, —N═, and —CCH3═;
R20 is selected from the group consisting of —H and —CN;
R21 is selected from the group consisting of —H, -alkyl, and -halogen;
R22 is selected from the group consisting of —NHCH2—, —CH2N(R6)CH2—, and
R23 is selected from the group consisting of —CH═, —N═, and —C(R36)═;
R24 is selected from the group consisting of —H, -alkyl, -halogen, and —CN;
R25 is selected from the group consisting of —H and -halogen;
R26 is selected from the group consisting of —CH2—, —NH—, —O—, —CH(R37)—, —C(CH3)2—, and
R27 is selected from the group consisting of —CH2— and —CO—;
R28 is selected from the group consisting of —H, -alkyl, and -carboalicyclyl;
R29 is selected from the group consisting of —O—, —CH(R38)—, and —N(R39)—;
R30 is selected from the group consisting of —CH2—, —O—, and —C(CH3)2—;
R31 is selected from the group consisting of —OH, -halogen, -carboaryl, —OCH3, —N(CH3)2, —CH2N(CH3)2, —OCH(CH3)2, and —CH2CH2R40CH3;
R32 is selected from the group consisting of -alkyl, —CCH3O, —CH2CH2OCH3, —CH2CONHCH3, and —R27CH2CH(CH3)2;
R33 is selected from the group consisting of -halogen, —OCH3, and cyclopropylmethoxy;
R34 is selected from the group consisting of -alkyl, -halogen, —OCH2CH3, —C(CH3)2R41, —CH2NHCCH3O, (pyrrolidin-1-yl)methyl, benzyl,
R35 is selected from the group consisting of —CCH3O, —R27CH2R42, and —SO2R43;
R36 is selected from the group consisting of -halogen and —CN;
R37 is selected from the group consisting of —NH2, —N(CH3)2, —CONHCH3, and —NHCCH3O;
R38 is selected from the group consisting of -halogen and —N(CH3)2;
R39 is -alkyl;
R40 is selected from the group consisting of —CH2— and —O—;
R41 is selected from the group consisting of —OH, -alkyl, and —CN;
R42 is selected from the group consisting of -alkyl and —COOH;
R43 is selected from the group consisting of -alkyl, -carboalicyclyl, and 3-fluorophenyl.

42 more elements

Facts

Application

18/161,184Filed 30 Jan 2023 · us provisional application

Priority

31 Jan 2022

Published

US 2023/0322695 A112 Oct 2023

Granted

10 Dec 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 285/06
Not condensed with other rings: 1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 35/00
Antineoplastic agents
C07D 285/10
Not condensed with other rings: 1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles