Heterocyclic sulfonamides, uses and pharmaceuticalcompositions thereof.

29-02-2012 дата публикации
Номер:
AP0201206072D0
Автор: FLIRI ANTON FRANZ JOSEPH, O'DONNELL CHRISTOPHER JOHN, SEGELSTEIN BARBARA EILEEN
Принадлежит:
Контакты:
Номер заявки: 07-06-20122
Дата заявки: 22-06-2010

[1]

Patents Granted (Contd.)

[2]

(30} Priority Data

[3]

(33) Country (31) Number (32) Date (72) Inventors

[4]

US 61/220,625 26.06.2009 FLIRI Anton Franz Joseph, United States of

[5]

America

[6]

GALLASCHUN Randall James, United States of America

[7]

O'DONNELL Christopher John, United States of America

[8]

(84) Designated State

[9]

BW GM GH ΚΕ

[10]

SL SD SZ ΤΖ

[11]

et al

[12]

(74) Representative

[13]

LS LR

[14]

UG ΖΜ

[15]

MW ΜΖ

[16]

ZW

[17]

ΝΑ

[18]

GALLOWAY & COMPANY

ZIMBABWE

[19]

(51)

[20]

(54)

[21]

(57)

[22]

International Classification: C07D213/65(2θθβ.οΐ)

[23]

C070 307/42 (2006.01)

[24]

C07D 405/12 (2006.01)

[25]

C07D 409/14 (2006.01)

[26]

C07C311/07(2006Al)

[27]

Α61Κ31/381 (2006.01)

[28]

Α61Κ31/443 (2006.01)

[29]

Α61Κ31/4709 (2006.01)

Title

[30]

C07D 307/22 (2006.01) C07D 333/38 (2006.01)

[31]

C07D 409/12 (2006.01)

[32]

C07D295/096 (2006.01)

[33]

Α61Κ31/341 (2006.01)

[34]

Α61Κ31/402(2006.01)

[35]

Α61Κ31/4453 (2006.01)

[36]

Heterocyclic sulfonamides, uses and pharmaceutical compositions thereof

[37]

Abstract

[38]

The invention is directed to a class of compounds, including the

[39]

pharmaceutically acceptable salts of the compounds, having the structure of

[40]

[41]

formula (I) as defined in the specification. The invention is also directed to

[42]

compositions containing and uses of the compounds of formula I.

[43]

(56) Documents Cited :

[44]

WO 2007/090840 Al

[45]

US 2003/073708 Al ΕΡ 1 101 755 Al

[46]

FORM 25 (12) PATENT (19) ΑΡ

[47]

(11) Patent No : ΑΡ 3066 (73) Applicants)

[48]

(21) Application No : AP/P/2012/006072 235 East 42nd Street, New York, New York 10017, United PFIZER INC. (22) Filing Date : 22.06.2010 States of America

[49]

(24) Date of Grant & (45) Publication : 24.12.2014



[50]

as defined in the specification. The invention is also directed to compositions containing and uses of the compounds of formula I.



A compound of formula I, or a pharmaceutically acceptable salt thereof,

wherein each R1 and each R2 and each R7 is independently selected from the group consisting of hydrogen, halogen, hydroxyl, -CF3, -CN, -(C=O)R8, -O-(C=O)-R8, -(NR8)-(C=O)-R8, -(C=O)-OR8, -(C=O)-N(R8)2, -OR8, -O-(C=O)-OR8, -O-(C=O)-N(R8)2, -NO2, -N(R8)2, -(NR8)-SO2-R8, -S(O)wR8, -SO2-N(R8)2, (C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, and (C3-C10)cycloalkyl; wherein said (C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, or (C3-C10)cycloalkyl are each independently optionally substituted with one, two, three or four R9;

w is 0, 1 or 2;

m is zero, one, two or three;

n is zero, one, two or three;

p is zero, one, two or three;

q is zero;

s is one and t is one; or one of s or t is one and the other of s or t is two;

R3 is hydrogen or (C1-C6)alkyl;

each R4 is independently selected from hydrogen, or (C1-C6)alkyl; wherein said (C1-C6)alkyl may be optionally substituted with one, two, three or four halogen, -CN, or - OR9;

or two R4 groups on the same carbon atom may be taken together to form an oxo (=O) radical or a (C3-C6)spirocycloalkyl;

R5 is hydrogen, or (C1-C6)alkyl;

R6 is (C1-C5)alkyl-SO2;

Each R8 is independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, and (C3-C10)cycloalkyl; wherein said (C1-C6)alkyl may be optionally substituted with one, two or three substituents independently selected from hydrogen, halo, -CN, perfluoro(C1-C6)alkyl, hydroxy, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino, (C1-C6)alkoxy, perfluoro(C1-C6)alkoxy, HO-(C=O)-, (C1-C6)alkyl-O-(C=O)-, formyl, (C1-C6)alkyl-(C=O)-, H2N-(C=O)-, (C1-C6)alkyl]-(NH)-(C=O)-, [(C1-C6)alkyl]2N-(C=O)-, (C1-C6)alkyl-(C=O)-O-, H(C=O)-NH-, (C1-C6)alkyl(C=O)-NH-, (C1-C6)alkyl(C=O)-[N((C1-C6)alkyl)]-, (C1-C6)alkyl-SO2-, (C1-C6)alkyl-SO2-NH-, (C1-C6)alkyl-SO2-[N((C1-C6)alkyl)]-, H2N-SO2-, [(C1-C6)alkyl]-NH-SO2-, and [(C1-C6)alkyl]2N-SO2-; wherein said (C1-C6)alkyl may be additionally optionally substituted with an optionally substituted (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, or (C3-C10)cycloalkyl; wherein said optional substituents may be independently substituted with from one, two, three or four radicals independently selected from halogen, hydroxyl, -CF3, -CN, (C1-C3)alkyl, (C1-C3)alkoxy, and amino; wherein each of said R8 (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl or (C3-C10)cycloalkyl substituents may be optionally additionally substituted with one, two, three or four radicals independently selected from halogen, hydroxyl, -CF3, -CN, (C1-C3)alkyl, (C1-C3)alkoxy and amino;

each R9 is independently selected from the group consisting of halogen, hydroxyl, -CF3, -CN, -(C=O)R10, -O-(C=O)-R10, -(NR10)-(C=O)-R10, -(C=O)-OR10, -(C=O)-N(R10)2, -OR10, -O-(C=O)-OR10, -O-(C=O)-N(R10)2, -NO2, -N(R10)2, - (NR10)-SO2-R10, -S(O)wR10, -SO2-N(R10)2;

each R10 is independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl and (C3-C10)cycloalkyl; wherein said (C1-C6)alkyl may be optionally substituted with one, two or three substituents independently selected from hydrogen, halo, -CN, perfluoro(C1-C6)alkyl, hydroxy, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino,

(C1-C6)alkoxy, perfluoro(C1-C6)alkoxy, HO-(C=O)-, (C1-C6)alkyl-O-(C=O)-, formyl, (C1-C6)alkyl-(C=O)-, H2N-(C=O)-, (C1-C6)alkyl]-(NH)-(C=O)-, [(C1-C6)alkyl]2N-(C=O)-, (C1-C6)alkyl-(C=O)-O-, H(C=O)-NH-, (C1-C6)alkyl(C=O)-NH-, (C1-C6)alkyl(C=O)-[N((C1-C6)alkyl)]-, (C1-C6)alkyl-SO2-, (C1-C6)alkyl-SO2-NH-, (C1-C6)alkyl-SO2-[N((C1-C6)alkyl)]-, H2N-SO2-, [(C1-C6)alkyl]-NH-SO2-, and [(C1-C6)alkyl]2N-SO2-; wherein said (C1-C6)alkyl may also be additionally optionally substituted with an optionally substituted (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl or (C3-C10)cycloalkyl; wherein said optional substituents may be independently substituted with from one, two, three or four radicals independently selected from halogen, hydroxyl, -CF3, -CN, (C1-C3)alkyl, (C1-C3)alkoxy, and amino; wherein each of said R10 (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, or (C3-C10)cycloalkyl substituents may be optionally additionally substituted with one, two, three or four radicals independently selected from halogen, hydroxyl, -CF3, -CN, (C1-C3)alkyl, (C1-C3)alkoxy, and amino;

R11 is hydrogen or (C1-C6)alkyl;

ring "A" is (C6-C10)aryl, (C1-C9)heteroaryl, (C4-C10)cycloalkyl, or (C1-C9)heterocycloalkyl; wherein two of said R1 substituents on said (C4-C10)cycloalkyl and (C1-C9)heterocycloalkyl may optionally be attached to the same carbon atom and may optionally be taken together to be oxo;

ring "B" is (C6-C10)aryl, (C1-C9)heteroaryl, (C4-C10)cycloalkyl, or (C1-C9)heterocycloalkyl;

"X" is -O- or >C(R4)2;

"Y" is absent; and

"Z" is -O-.

A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is of Formula:

A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is of Formula:

A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein X is -0-.

A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein ring "A" is phenyl; n is zero, one or two; R1 is selected from the group consisting of hydrogen, halogen, hydroxyl, -CF3, - CN, -(C=O)R8, -O-(C=O)-R8, -(NR8)-(C=O)-R8, -(C=O)-OR8, -(C=O)-N(R8)2, -OR8, -O-(C=O)-OR8, -O-(C=O)-N(R8)2, -NO2, -N(R8)2, -(NR8)-SO2-R8, -S(O)wR8, -SO2-N(R8)2, and (C1-C6)alkyl; wherein said (C1-C6)alkyl is optionally substituted with one, two, three or four R9.

A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein ring "A" is (C1-C9)heteroaryl; n is zero, one or two; and wherein R1 is selected from the group consisting of hydrogen, halogen, hydroxyl, -CF3, -CN, -(C=O)R8, -O-(C=O)-R8, -(NR8)-(C=O)-R8, -(C=O)-OR8, -(C=O)-N(R8)2, -OR8, -O-(C=O)-OR8, -O-(C=O)-N(R8)2, -NO2, -N(R8)2, -(NR8)-SO2-R8, -S(O)wR8, -SO2-N(R8)2, and (C1-C6)alkyl; wherein said (C1-C6)alkyl is optionally substituted with one, two, three or four R9.

A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein ring "B" is phenyl; m is zero or one; R2 is hydrogen, halogen, hydroxyl, -CF3, -CN, -(C=O)R8, -O-(C=O)-R8, -(NR8)-(C=O)-R8, -(C=O)-OR8, -(C=O)-N(R8)2, -OR8, -O-(C=O)-OR8, -O-(C=O)-N(R8)2, -NO2, -N(R8)2, -(NR8)-SO2-R8, -S(O)wR8, -SO2-N(R8)2, and (C1-C6)alkyl; wherein said (C1-C6)alkyl is optionally substituted with one, two, three or four R9.

A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein ring "B" is (C1-C9)heteroaryl; m is zero or one; R2 is hydrogen, halogen, hydroxyl, -CF3, -CN, -(C=O)R8, -O-(C=O)-R8, -(NR8)-(C=O)-R8, - (C=O)-OR8, -(C=O)-N(R8)2, -OR8, -O-(C=O)-OR8, -O-(C=O)-N(R8)2, -NO2, -N(R8)2, - (NR8)-SO2-R8, -S(O)wR8, -SO2-N(R8)2, and (C1-C6)alkyl; wherein said (C1-C6)alkyl is optionally substituted with one, two, three or four R9.

A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen.

A compound according to any of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen and R4 is hydrogen.

A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is:

N-{1-[4-trans-({4-[(isopropylsulfonyl)amino]tetrahydrofuran-3-yl}oxy)phenyl]pyrrolidin-3-yl}acetamide;

N-[(3S,4S)-4-(biphenyl-4-yloxy)tetrahydrofuran-3-yl]propane-2-sulfonamide;

N-{(3S,4S)-4-[(2'-cyanobiphenyl-4-yl)oxy]tetrahydrofuran-3-yl}propane-2-sulfonamide;

N-{(3S,4S)-4-[4-(5-cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide;

N-{(1S,2R)-2-[(2'-cyanobiphenyl-4-yl)oxy]cyclopentyl}propane-2-sulfonamide;

N-{(1S,2R)-2-[4-(5-cyano-2-thienyl)phenoxy]cyclopentyl}propane-2-sulfonamide;

N-{(1S,2R)-2-[(2'-cyanobiphenyl-4-yl)oxy]cyclohexyl}propane-2-sulfonamide;

cis-N-[4-(4-pyridin-3-ylphenoxy) tetrahydro furan-3-yl]propane-2-sulfonamide;

cis-N-{4-[4-(2-thienyl) phenoxy] tetrahydro furan-3-yl}propane-2-sulfonamide;

N-{(3S,4S)-4-[(2'-cyano -4'-fluoro biphenyl-4-yl)oxy]tetra hydrofuran-3-yl}propane-2-sulfonamide;

N-{(3S,4S)-4-[(4'-fluoro biphenyl-4-yl)oxy]tetra hydrofuran-3-yl}propane-2-sulfonamide;

N-{(3S,4S)-4-[(2'-ethoxy-4'-fluoro biphenyl-4-yl)oxy]tetra hydrofuran-3-yl}propane-2-sulfonamide;

cis-N-[4-{[6-(5-cyano-2-thienyl) pyridin-3-yl]oxy}tetra hydrofuran-3-yl]propane-2-sulfonamide;

cis-N-{4-[4-(3-thienyl) phenoxy] tetrahydro furan-3-yl}propane-2-sulfonamide;

2-cyano-4'-({(1R,2S)-2-[(isopropyl sulfonyl) amino] cyclopentyl}oxy) biphenyl-4-carboxylic acid;

N-{(1S,2R)-2-[(2'-cyano-2,4'-difluoro biphenyl-4-yl)oxy]cyclopentyl}propane-2-sulfonamide;

N-{(1S,2R)-2-[(2'-ethoxy-2-fluoro biphenyl-4-yl)oxy]cyclopentyl}propane-2-sulfonamide; sulfonamide;

N-{(1S,2R)-2-[(2'-cyano-2-fluoro biphenyl-4-yl)oxy]cyclohexyl} propane-2-sulfonamide;

N-{(1S,2R)-2-[(2'-cyano-2,4'-difluoro biphenyl-4-yl)oxy] cyclohexyl} propane-2-sulfonamide;

N-{(1S,2R)-2-[4-(5-cyano-2-thienyl)-3-fluoro phenoxy] cyclohexyl} propane-2-sulfonamide;

N-[(1S,2R)-2-(4-pyrrolidin-1-ylphenoxy) cyclohexyl] propane-2-sulfonamide;

N-[(1S,2R)-2-({6-[2-(2,2,2-trifluoro ethoxy) phenyl] pyridin-3-yl}oxy) cyclohexyl] propane-2-sulfonamide;

N-[(1S,2R)-2-({6-[2-(trifluoro methoxy) phenyl] pyridin-3-yl}oxy) cyclohexyl] propane-2-sulfonamide; or

N-[(1S,2R)-2-{[6-(5-cyano-2-thienyl) pyridin-3-yl]oxy} cyclohexyl] propane-2-sulfonamide.

A compound according to claim 1 which is N-{(3S,4S)-4-[4-(5-cyano-2-thienyl)phenoxy]-tetrahydrofuran-3-yl}propane-2-sulfonamide.

A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is N-{(3S,4S)-4-[4-(5-cyano-2-thienyl)phenoxy]-tetrahydrofuran-3-yl}propane-2-sulfonamide.

A compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention in a mammal of a condition selected from the group consisting of acute neurological and psychiatric disorders, stroke, cerebral ischemia, spinal cord trauma, head trauma, perinatal hypoxia, cardiac arrest, hypoglycemic neuronal damage, dementia, Alzheimer's disease, Huntington's Chorea, amyotrophic lateral sclerosis, ocular damage, retinopathy, cognitive disorders, idiopathic and drug- induced Parkinson's disease, muscular spasms and disorders associated with muscular spasticity including tremors, epilepsy, convulsions, migraine, urinary incontinence, substance tolerance, substance withdrawal, psychosis, schizophrenia, anxiety, mood disorders, trigeminal neuralgia, hearing loss, tinnitus, macular degeneration of the eye, emesis, brain edema, pain, tardive dyskinesia, sleep disorders, attention deficit/hyperactivity disorder, attention deficit disorder, and conduct disorder.

A pharmaceutical composition comprising a compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.



CPC - классификация

CC0C07C07CC07C2C07C26C07C260C07C2601C07C2601/C07C2601/0C07C2601/08C07C2601/1C07C2601/14C07C3C07C30C07C307C07C307/C07C307/0C07C307/02C07C31C07C311C07C311/C07C311/0C07C311/07C07DC07D2C07D20C07D207C07D207/C07D207/0C07D207/08C07D21C07D213C07D213/C07D213/6C07D213/65C07D29C07D295C07D295/C07D295/0C07D295/09C07D295/096C07D3C07D30C07D307C07D307/C07D307/2C07D307/22C07D307/4C07D307/42C07D33C07D333C07D333/C07D333/3C07D333/38C07D4C07D40C07D405C07D405/C07D405/1C07D405/12C07D407C07D407/C07D407/1C07D407/12C07D409C07D409/C07D409/0C07D409/04C07D409/1C07D409/12C07D409/14

IPC - классификация

AA6A61A61KA61K3A61K31A61K31/A61K31/3A61K31/34A61K31/341A61K31/4A61K31/47A61K31/470A61K31/4709CC0C07C07CC07C3C07C31C07C311C07C311/C07C311/0C07C311/07C07DC07D2C07D21C07D213C07D213/C07D213/6C07D213/65C07D29C07D295C07D295/C07D295/0C07D295/09C07D295/096C07D4C07D40C07D409C07D409/C07D409/1C07D409/14