Sulfonamide compound

Patent metadata

Field	Value
Publication number	US-9487488-B2
Application number	US-201314428267-A
Country	US
Kind code	B2
Filing date	Sep 13, 2013
Priority date	Sep 14, 2012
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

The present invention provides novel sulfonamide compounds having TRPM8 antagonistic activity which are useful as medicaments. Specifically, the present invention provides a sulfonamide compound of the formula (I):

wherein Ring A is the following formula (i), (ii), or (ix):

R 4 is optionally substituted alkyl,
X 1 and X 2 are each independently tetrazolyl, tetrazolinonyl, optionally substituted triazolyl, triazolinonyl, oxadiazolonyl, optionally substituted alkanoylaminomethyl, or optionally substituted alkylsulfonylaminomethyl, or
R 4 and X 2 combine with each other at their terminals together with the adjacent benzene to form indazolinonyl or benzoisoxazolonyl, and
the other symbols are the same as described in the specification,
or a pharmaceutically acceptable salt thereof.

First claim

The invention claimed is:

1. A compound of the formula (I):

wherein R 1 is optionally substituted alkyl or optionally substituted cycloalkyl,
R 2 is a hydrogen atom or optionally substituted cycloalkyl,
R 3 is optionally substituted alkyl or optionally substituted alkoxy,
Z is CH or N,
Ring A is the following formula (i), (ii), or (ix):

R 4 is optionally substituted alkyl,
R 6 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkoxy, optionally substituted alkylamino, optionally substituted dialkylamino, an optionally substituted monocyclic nitrogen-containing non-aromatic heterocyclic group, optionally substituted phenyl, or halogen,
R 7 is a hydrogen atom, optionally substituted alkyl, or halogen,
X 1 and X 2 are each independently tetrazolyl, tetrazolinonyl, optionally substituted triazolyl, triazolinonyl, oxadiazolonyl, optionally substituted alkanoylaminomethyl, or optionally substituted alkylsulfonylaminomethyl, or
R 4 and X 2 combine with each other at their terminals together with the adjacent benzene to form indazolinonyl or benzoisoxazolonyl, and
Y 1 and Y 2 are both CH, or one of Y 1 and Y 2 is CH, and the other is N, or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein
R 1 is C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, or C 3 -C 7 cycloalkyl, and
R 2 is a hydrogen atom or C 3 -C 7 cycloalkyl,

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein R 3 is C 1 -C 6 halogenoalkyl or C 1 -C 6 halogenoalkoxy, or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein
R 1 is C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, or C 3 -C 7 cycloalkyl,
R 2 is a hydrogen atom or C 3 -C 7 cycloalkyl, and
R 3 is C 1 -C 6 halogenoalkyl or C 1 -C 6 halogenoalkoxy,

or a pharmaceutically acceptable salt thereof.

5. The compound according to any one of claims 1 - 4 , wherein
Ring A is the formula (i) or formula (ii),
R 4 is C 1 -C 6 alkyl, and
X 1 and X 2 are each independently tetrazolyl, tetrazolinonyl, triazolyl, C 1 -C 6 alkyltriazolyl, C 1 -C 6 halogenoalkyltriazolyl, triazolinonyl, oxadiazolonyl, C 2 -C 7 alkanoylaminomethyl, C 1 -C 6 alkylsulfonylaminomethyl, or C 1 -C 6 halogenoalkylsulfonylaminomethyl, or
R 4 and X 2 combine with each other at their terminals together with the adjacent benzene to form indazolinonyl or benzoisoxazolonyl,

or a pharmaceutically acceptable salt thereof.

6. The compound according to any one of claims 1 - 4 , wherein
Ring A is the formula (i) or formula (ii),
R 4 is C 1 -C 6 alkyl, and
X 1 and X 2 are each independently tetrazolyl, tetrazolinonyl, triazolyl, C 1 -C 6 alkyltriazolyl, C 1 -C 6 halogenoalkyltriazolyl, triazolinonyl, or oxadiazolonyl,
R 4 and X 2 combine with each other at their terminals together with the adjacent benzene to form indazolinonyl or benzoisoxazolonyl,

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 , wherein
R 1 is C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, or C 3 -C 7 cycloalkyl,
R 2 is a hydrogen atom or C 3 -C 7 cycloalkyl,
R 3 is C 1 -C 6 halogenoalkyl or C 1 -C 6 halogenoalkoxy,
Ring A is the formula (i) or (ii),
R 4 is C 1 -C 6 alkyl, and
X 1 and X 2 are each independently tetrazolyl, tetrazolinonyl, triazolyl, alkyltriazolyl, C 1 -C 6 halogenoalkyltriazolyl, triazolinonyl, oxadiazolonyl, C 2 -C 7 alkanoylaminomethyl, C 1 -C 6 alkylsulfonylaminomethyl, or C 1 -C 6 halogenoalkylsulfonylaminomethyl, or
R 4 and X 2 combine with each other at their terminals together with the adjacent benzene to form indazolinonyl or benzoisoxazolonyl,

or a pharmaceutically acceptable salt thereof.

8. The compound according to any one of claims 1 - 4 , wherein
Ring A is the formula (i) or formula (ii),
R 4 is C 1 -C 6 alkyl, and
X 1 and X 2 are each independently the following formula (iii), (iv), (v), (vi), or (vii):

wherein R 5 is a hydrogen atom, C 1 -C 6 alkyl, or C 1 -C 6 halogenoalkyl, and V 1 is NH or O, or
R 4 and X 2 combine with each other at their terminals together with the adjacent benzene to form the following formula (viii):

wherein V 2 is NH or O,
or a pharmaceutically acceptable salt thereof.

9. The compound according to any one of claims 1 - 4 , wherein
Ring A is the formula (i) or formula (ii),
R 4 is C 1 -C 6 alkyl,
X 1 and X 2 are each independently the following formula (iii), (iv), (v-a), or (vii-a):

wherein R 5a is a hydrogen atom or C 1 -C 6 alkyl, or
R 4 and X 2 combine with each other at their terminals together with the adjacent benzene to form the following formula (vii-a):

Y 1 is CH, and
Y 2 is CH or N,

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 , wherein
R 1 is cyclopropyl,
R 2 is a hydrogen atom,
R 3 is C 1 -C 6 fluoroalkyl or C 1 -C 6 fluoroalkoxy, and
Ring A is the formula (i) or formula (ii),

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 , wherein
R 1 is trifluoromethyl,
R 2 is a hydrogen atom,
R 3 is C 1 -C 6 fluoroalkoxy,
Z is CH, and
Ring A is the formula (i) or formula (ii),

or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 , wherein
R 1 is methyl,
R 2 is cyclopropyl,
R 3 is C 1 -C 6 fluoroalkoxy,
Z is CH, and
Ring A is the formula (i) or formula (ii),

or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 , wherein
R 1 is C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, or C 3 -C 7 cycloalkyl,
R 2 is a hydrogen atom or C 3 -C 7 cycloalkyl,
R 3 is C 1 -C 6 halogenoalkyl or C 1 -C 6 halogenoalkoxy,
Z is CH or N,
Ring A is the formula (i) or (ii),
R 4 is C 1 -C 6 alkyl,
X 1 and X 2 are each independently the following formula (iii), (iv), (v-a), or (vii-a)

wherein R 5a is a hydrogen atom or C 1 -C 6 alkyl, or
R 4 and X 2 combine with each other at their terminals together with the adjacent benzene to form the following formula (viii-a):

Y 1 is CH, and
Y 2 is CH or N,

or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 13 wherein
R 1 is C 1 -C 6 halogenoalkyl or C 3 -C 7 cycloalkyl,
R 2 is a hydrogen atom,
R 3 is C 1 -C 6 halogenoalkoxy,
Ring A is the formula (i),
X 1 is formula (iv), (v-a), or (vii-a), and
Z is CH,

or a pharmaceutically acceptable salt thereof.

15. A compound selected from th

Assignees

• Mitsubishi Tanabe Pharma Corp

Inventors

• Kato Taku
• Sakamoto Toshiaki
• Kubo Akira
• Sawamoto Daisuke

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/06

  Antimigraine agents · CPC title

• A61P29/02

  without antiinflammatory effect · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title