Pyrazole derivative

• US 7,285,554 B2
• Filed: 04/07/2006
• Issued: 10/23/2007
• Est. Priority Date: 10/13/1997
• Status: Expired due to Fees

• Current Assignee: Astellas Pharma Incorporated
• Original Assignee: Astellas Pharma Incorporated
• Inventors: Takeuchi, Makoto, Okamoto, Yoshinori, Kubota, Hirokazu, Ishikawa, Jun, Yonetoku, Yasuhiro, Kawazoe, Souichirou, Sugasawa, Keizo, Toyoshima, Akira, Funatsu, Masashi
• Primary Examiner(s): RAO, DEEPAK R
• Application Number:
  US11/399,379
• Publication Number:
  US 20060264430A1
• Time in Patent Office: 564 Days
• Field of Search: 548/127, 548/200, 548/236, 548/312.4, 548/364.1, 548/365.7, 548/375.1, 546/211, 546/275.4, 544/405, 514/255.05, 514/326, 514/341, 514/361, 514/365, 514/374, 514/397, 514/406
• US Class Current: 514/255.05
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/14 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/56 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

Drugs, in particular, pyrazole derivatives represented by the following general formula (I) which have a calcium release-activated calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-activated calcium channel inhibitors containing the above compounds as the active ingredient,

(in the formula, each symbol has the following meaning:
D: pyrazolyl which may have 1 to 3 substituents selected from the group consisting of -Alk, -lower alkenyl, -lower alkynyl, -halogeno-lower alkyl, -Alk-cycloalkyl, -Alk-O-Alk, -cycloalkyl, —O-Alk, —COOH, —COO-Alk and -Hal,
n: 0 or 1,
B: phenylene, a nitrogen-containing, divalent, saturated ring group, or a monocyclic, divalent heteroaromatic ring group which may be substituted with Alk,
X: —NR¹—CR²R³—, —CR²R³—NR¹—, —NR¹—SO₂—, —SO₂—NR¹— or —CR⁴═CR⁵—, and
A: benzene ring which may have one or more substituents; mono-, di- or tricyclic fused heteroaryl which may have one or more substituents; cycloalkyl which may have one or more substituents; a nitrogen-containing, saturated ring group which may have one or more substituents; lower alkenyl which may have one or more substituents; lower alkynyl which may have one or more substituents; or Alk which may have one or more substituents).

Claims

1. A pyrazole compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof

2. The pyrazole compound or pharmaceutically acceptable salt thereof according to claim 1, wherein

D is 1H-pyrazol-1-yl, 1H-pyrazol-3-yl or 1H-pyrazol-5-yl, each of which may have 1 to 2 substituents selected from -Alk, halogeno-lower alkyl- and —

COO-Alk, and

A is phenyl which may have one or more substituents selected from the group consisting of -Alk, -Hal, —

NH₂, —

N(Alk)₂, —

NO₂, —

CN, —

OH, —

O-Alk and —

COO-Alk;

mono- or di-cyclic fused heteroaryl selected from the group consisting of thienyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, tetrazolyl, triazolyl, thiadiazolyl, pyridyl, pyrazinyl and isoquinolyl, which may be substituted with one or more Alk;

or cycloalkyl.

3. The pyrazole compound or pharmaceutically acceptable salt thereof according to claim 1, wherein D is 1H-pyrazol-1-yl, 1H-pyrazol-3-yl or 1H-pyrazol-5-yl substituted with at least one trifluoromethyl group.

4. The pyrazole compound or pharmaceutically acceptable salt thereof according to claim 1, wherein D is 1H-pyrazol-5-yl substituted with at least one trifluoromethyl group or 1H-pyrazol-1-yl substituted with at least one trifluoromethyl group.

5. The pyrazole compound or pharmaceutically acceptable salt thereof according to claim 1, wherein D is 1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl and A is phenyl which may be substituted with Hal.

6. The pyrazole compound or pharmaceutically acceptable salt thereof according to claim 1, wherein D is 3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl and A is monocyclic heteroaryl selected from the group consisting of thiazolyl, thiadiazolyl, thienyl and pyridyl, which may be substituted with one or more Alk.

7. A pharmaceutical composition which comprises a pharmaceutically effective amount of a pyrazole compound represented by the following general formula (I′

) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier

8. The pharmaceutical composition according to claim 7, wherein D is 1H-pyrazol-1-yl, 1H-pyrazol-3-yl or 1H-pyrazol-5-yl substituted with at least one trifluoromethyl group.

9. The pharmaceutical composition according to claim 7, wherein D is 1H-pyrazol-5-yl substituted with at least one trifluoromethyl group or 1H-pyrazol-1-yl substituted with at least one trifluoromethyl group.

10. The pharmaceutical composition according to claim 7, wherein D is 1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl and A is phenyl which may be substituted with Hal.

11. The pharmaceutical composition according to claim 7, wherein D is 3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl and A is monocyclic heteroaryl selected from the group consisting of thiazolyl, thiadiazolyl, thienyl and pyridyl, which may be substituted with Alk.

12. A method for treating bronchial asthma, which comprises administering a pharmaceutical composition comprising a pyrazole compound represented by the following general formula (I′

)

13. A method for treating rheumatoid arthritis, which comprises administering a pharmaceutical composition comprising a pyrazole compound represented by the following general formula (I′

)