IP Library › Granted Patent US 7,842,836
Granted Patent B2
US 7,842,836 · App. 11/734,234 · Granted Nov 30, 2010

N-aryl-N'alkyl sulfamides as MEK inhibitors

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 7,842,836
App. No.
11/734,234
Granted
Nov 30, 2010
Kind
B2
Abstract

This invention concerns N-(ortho phenylaminoaryl), N′-alkyl sulfamides which are inhibitors of MEK and are useful in the treatment of cancer and other hyperproliferative diseases.

Claims (215)

1. A compound of formula I or a pharmaceutically acceptable salt thereof

wherein

B is H, C 1 -C 4 alkyl, or C 2 -C 6 alkenyl;

wherein said C 1 -C 4 alkyl is optionally substituted with one or two hydroxy groups;

A and A′ are each independently H, C 1 -C 4 alkyl, or C 2 -C 6 alkenyl;

wherein each C 1 -C 4 alkyl is independently optionally substituted with one or two hydroxy groups; or

A and A′ together with the carbon atom to which they are attached, form a cyclopropyl, cyclobutyl, or cyclopentyl group, optionally substituted with at least one methyl, hydroxy, or halogen;

R 1 is H or F;

R 2 is Br or I;

R 0 is OR 3 ;

wherein R 3 is H, C 1 -C 4 alkyl or phenyl;

wherein each C 1 -C 4 alkyl or phenyl group is independently optionally substituted with at least one halogen, hydroxy, azido, cyano, cyanomethyl, nitro, phenyl, difluoromethyl, trifluoromethyl, methoxy, or C 1 -C 4 alkoxy.

2. The compound of claim 1 , wherein

R 0 is OR 3 ; and

R 3 is C 1 -C 4 alkyl

optionally substituted with at least one halogen, methyl, trifluoromethyl, hydroxy, or alkoxy.

3. The compound of claim 1 , wherein

B is —H, —CH 3 , —CH 2 CH 2 OH, —CH 2 CH(OH)CH 2 OH, —(CH 2 ) 2 CH(OH)CH 2 OH, —CH 2 —CH═CH 2 or —CH 2 —CH 2 CH═CH 2 ; and

A and A′ are both H; or

A and A′ together with the carbon atom to which they are attached are

4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula I or a pharmaceutically acceptable salt thereof;

wherein

B is H, C 1 -C 4 alkyl, or C 2 -C 6 alkenyl;

wherein said C 1 -C 4 alkyl is optionally substituted with one or two hydroxy groups;

A and A′ are each independently H, C 1 -C 4 alkyl, or C 2 -C 6 alkenyl;

wherein each C 1 -C 4 alkyl is independently optionally substituted with one or two hydroxy groups; or

A and A′ together with the carbon atom to which they are attached, form a cyclopropyl, cyclobutyl, or cyclopentyl group, optionally substituted with at least one methyl, hydroxy, or halogen;

R 1 is H or F;

R 2 is Br or I;

R 0 is OR 3 ;

wherein R 3 is H, C 1 -C 4 alkyl or phenyl;

wherein each C 1 -C 4 alkyl or phenyl group is independently optionally substituted with at least one halogen, hydroxy, azido, cyano, cyanomethyl, nitro, phenyl, difluoromethyl, trifluoromethyl, methoxy, or C 1 -C 4 alkoxy.

5. A compound of formula I

wherein the compound is as recited in the following table:

CPD

#

—C(A)A'—

—B

R 0

R 1

R 2

1

—CH 2 —

—H

OCH 3

F

I

2

—CH 2 —

—CH 2 CH(OH)CH 2 OH

OCH 3

F

I

3

—CH 2 —CH 2 —CH ═CH 2

OCH 3

F

I

4

—CH 3

OCH 3

F

I

5

—CH 2 CH 2 OH

OCH 3

F

I

6

—(CH 2 ) 2 CH(OH)CH 2 OH

OCH 3

F

I

7

—(CH 2 ) 2 CH(OH)CH 2 OH

OCH 3

F

I

8

—(CH 2 ) 2 CH(OH)CH 2 OH

OCH 3

F

I

9

—CH 2 CH(OH)CH 2 OH

OCH 3

F

I

10

—H

OCH 3

F

I

11

—CH 2 CH(OH)CH 2 OH

OCH 3

F

I

12

—CH 2 —CH 2 —CH═CH 2

OCH 3

F

I

13

—CH 2 CH 2 OH

OCH 3

F

1

14

—CH 3

OCH 3

F

I

15

—CH 2 —

—H

OCH 3

H

I

16

—CH 2 —

—CH 2 CH(OH)CH 2 OH

OCH 3

H

Br

17

—CH 2 —CH 2 —CH═CH 2

OCH 3

H

I

18

—CH 3

OCH 3

H

Br

19

—CH 2 CH 2 OH

OCH 3

H

Br

20

—(CH 2 ) 2 CH(OH)CH 2 OH

OCH 3

H

Br

21

—(CH 2 ) 2 CH(OH)CH 2 OH

OCH 3

H

Br

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 5 or a pharmaceutically acceptable salt thereof.

7. The compound of claim 2 , wherein

B is —H, —CH 3 , —CH 2 CH 2 OH, —CH 2 CH(OH)CH 2 OH, —(CH 2 ) 2 CH(OH)CH 2 OH, —CH 2 —CH═CH 2 or —CH 2 —CH 2 CH═CH 2 ; and

A and A′ are both H; or

A and A′ together with the carbon atom to which they are attached are

8. The compound of claim 1 , wherein

B is —H, —CH 3 , —CH 2 CH 2 OH, —CH 2 CH(OH)CH 2 OH, —(CH 2 ) 2 CH(OH)CH 2 OH, —CH 2 —CH═CH 2 or —CH 2 —CH 2 CH═CH 2 .

9. The compound of claim 1 , wherein

A and A′ are both H.

10. The compound of claim 1 , wherein

A and A′ together with the carbon atom to which they are attached are

11. The compound of claim 1 , wherein R 3 is methyl.

12. The compound of claim 7 , wherein R 3 is methyl.

13. The compound of claim 8 , wherein R 3 is methyl.

14. The compound of claim 9 , wherein R 3 is methyl.

15. The compound of claim 10 , wherein R 3 is methyl.

16. A compound according to claim 5 , which is of formula I

wherein the compound is as recited in the following table:

CPD#

—C(A)A′—

—B

R 0

R 1

R 2

 1

—CH 2 —

—H

OCH 3

F

I

 2

—CH 2 —

—CH 2 CH(OH)CH 2 OH

OCH 3

F

I

15

—CH 2 —

—H

OCH 3

H

I

16

—CH 2 —

—CH 2 CH(OH)CH 2 OH

OCH 3

H

Br

or a pharmaceutically acceptable salt thereof.

17. A compound according to claim 5 , which is of formula I

wherein the compound is as recited in the following table:

CPD#

—C(A)A′—

—B

R 0

R 1

R 2

2

—CH 2 —

—CH 2 CH(OH)CH 2 OH

OCH 3

F

I

or a pharmaceutically acceptable salt thereof.

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Apr 8, 2025
From: BARCLAYS BANK PLC, AS COLLATERAL AGENT
To: SOLTA MEDICAL, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH IRELAND LIMITED (F/K/A/ VALEANT PHARMACEUTICALS IRELAND LIMITED); SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD; SANTARUS, INC.; MEDICIS PHARMACEUTICAL CORPORATION; HUMAX PHARMACEUTICAL S.A.; SOLTA MEDICAL IRELAND LIMITED; BAUSCH & LOMB MEXICO, S.A. DE C.V.; BAUSCH+LOMB OPS B.V.; BAUSCH HEALTH AMERICAS, INC.; BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH HOLDCO LIMITED; BAUSCH HEALTH MAGYARORSZAG KFT (A/K/A BAUSCH HEALTH HUNGARY LLC); BAUSCH HEALTH POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA (F/K/A VALEANT PHARMA POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA); BAUSCH HEALTH US, LLC; BAUSCH HEALTH, CANADA INC. / SANTE BAUSCH, CANADA INC.; ICN POLFA RZESZOW SPOLKA AKCYJNA (A/K/A ICN POLFA RZESZOW S.A.); ORAPHARMA, INC.; PRZEDSIEBIORSTWO FARMACEUTYCZNE JELFA SPOLKA AKCYJNA (A/K/A PRZEDSIEBIORSTWO FARMACEUTYCZNE JELFA S.A.); SOLTA MEDICAL DUTCH HOLDINGS B.V.; V-BAC HOLDING CORP.; VRX HOLDCO LLC; 1261229 B.C. LTD.; 1530065 B.C. LTD.
Reel/Frame 070778/0199 →
NOTICE OF SUCCESSION OF AGENCY Recorded Jan 9, 2015
From: GOLDMAN SACHS LENDING PARTNERS, LLC
To: BARCLAYS BANK PLC, AS SUCCESSOR AGENT
Reel/Frame 034749/0689 →
CORRECTIVE PARTIAL RELEASE OF SECURITY INTEREST IN PATENTS Recorded Oct 12, 2011
From: GOLDMAN SACHS LENDING PARTNERS LLC
To: VALEANT PHARMACEUTICALS INTERNATIONAL; ATON PHARMA, INC.; CORIA LABORATORIES, LTD.; DOW PHARMACEUTICAL SCIENCES; VALEANT PHARMACEUTICALS NORTH AMERICA LLC,; PRESTWICK PHARMACEUTICALS, INC.; VALEANT BIOMEDICALS, INC.
Reel/Frame 027052/0883 →
SECURITY AGREEMENT Recorded Jul 18, 2011
From: VALEANT PHARMACEUTICALS INTERNATIONAL, A DELAWARE CORPORATION; ATON PHARMA, INC., A DELAWARE CORPORATION; CORIA LABORATORIES, LTD., A DELAWARE CORPORATION; DOW PHARMACEUTICAL SCIENCES, INC., A DELAWARE CORPORATION; VALEANT PHARMACEUTICALS NORTH AMERICA LLC, A DELAWARE LLC; PRESTWICK PHARMACEUTICALS, INC., A DELAWARE CORPORATION; VALEANT BIOMEDICALS, INC., A DELAWARE CORPORATION
To: GOLDMAN SACHS LENDING PARTNERS LLC, AS COLLATERAL AGENT
Reel/Frame 026606/0061 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 14, 2007
From: YAN, SHUNQI; VERNIER, JEAN-MICHEL; HONG, ZHI
To: ARDEA BIOSCIENCES
Reel/Frame 019290/0719 →