Nitrogen-containing heterocyclic derivatives and drugs containing the same as the active ingredient

• US 7,910,741 B2
• Filed: 03/12/2004
• Issued: 03/22/2011
• Est. Priority Date: 03/14/2003
• Status: Expired due to Fees

• Current Assignee: ONO Pharmaceutical Company Limited
• Original Assignee: ONO Pharmaceutical Company Limited
• Inventors: Shibayama, Shiro, Takaoka, Yoshikazu, Nishizawa, Rena
• Primary Examiner(s): Desai; Rita J
• Assistant Examiner(s): Mabry; John
• Application Number:
  US10/549,120
• Publication Number:
  US 20060178399A1
• Time in Patent Office: 2,566 Days
• Field of Search: 546/194, 546/223, 546/208, 546/210, 514/317, 514/318, 514/326
• US Class Current: 546/194
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 211/22 : by oxygen atoms
• CPC Class Codes: C07D 211/32 : by oxygen atoms
• CPC Class Codes: C07D 211/34 : with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/48 : having an acyclic carbon atom attached in position 4
• CPC Class Codes: C07D 211/58 : attached in position 4
• CPC Class Codes: C07D 211/62 : attached in position 4
• CPC Class Codes: C07D 211/66 : having a hetero atom as the second substituent in position 4
• CPC Class Codes: C07D 211/72 : with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
• CPC Class Codes: C07D 211/74 : Oxygen atoms
• CPC Class Codes: C07D 241/04 : having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 295/108 : to an acyclic saturated chain
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/08 : linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 487/08 : Bridged systems

Abstract

A compound represented by the following general formula (I), its salt, solvates thereof or prodrugs thereof:

(wherein each symbol is as defined in the description.) The compounds represented by the general formula (I) are useful in preventing and/or treating various inflammatory diseases (asthma, nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, rhinitis, conjunctivitis, ulcerative colitis, etc.), immunological diseases (autoimmune diseases, rejection in organ transplantation, immunosuppression, psoriasis, multiple sclerosis, etc.), infection with human immunodeficiency virus (acquired immunodeficiency syndrome, etc.), allergic diseases (atopic dermatitis, urticaria, allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis, etc.), ischemic reperfusion injury, acute respiratory distress syndrome, shock accompanying bacterial infection, diabetes, cancer metastasis and so on.

Claims

1. A compound represented by formula (I):

2. A pharmaceutical composition, which comprises the compound represented by formula (I) according to claim 1 or a salt thereof, and a pharmaceutically acceptable carrier.

3. The compound according to claim 1, which is represented by formula (Id):

4. The compound according to claim 3,

wherein ring A^1b is benzene which may have a substituent(s) of methyl and/or a halogen atoms(s).

5. The compound according to claim 3, wherein ring B^1b is pyridine which has a substituent(s) of methyl and/or a halogen atom(s).

6. The compound according to claim 3, wherein

R⁵¹ is

(1) C1-6 alkyl which may have a substituent(s) selected from the group consisting of (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, and (e) thienyl, tetrahydropyranyl, imidazolyl, or pyridyl, each of which may have methyl and/or trifluromethyl, (2) C2-10 alkenyl, (3) C2-10 alkynyl, or (4) phenyl which may have methyl and/or a halogen atom(s).

7. The compound according to claim 3,

wherein R⁵² is (1) C1-6 alkyl which may have a substituent(s) selected from the group consisting of (a) hydroxy, (b) methoxy, (c) carboxy, (d) cyclohexyl, (e) phenyl, and (f) oxo, (2) C3-8 cycloalkyl or phenyl, each of which may have a substituent(s) selected from the group consisting of C1-4 alkyl, hydroxy, cyano, oxo, carbamoyl, N-methylaminocarbonyl, carboxy, a halogen atom(s), methoxy, trifluoromethoxy, methylthio, methylsulfonyl, acetylamino, acetyl, trifluoromethyl, and methylsulfonylamino, (3) cyclopentenyl, or (4) thienyl, pyrazolyl, tetrahydropyranyl, piperidinyl, pyridyl, quinolyl, or indolyl, each of which may have a substituent(s) of C1-4 alkyl, hydroxy, oxo, a halogen atom(s), and/or trifluoromethyl.

8. The compound according to claim 6, wherein R⁵¹ is C1-6 alkyl.

9. The compound according to claim 7, wherein R⁵² is phenyl which may have a substituent(s) of methyl, ethyl, hydroxy, cyano, carbamoyl, N-methylaminocarbonyl, carboxy, a halogen atom(s), methoxy, trifluoromethoxy, methylthio, methylsulfonyl, acetylamino, acetyl, trifluoromethyl, and/or methylsulfonylamino.

10. A compound represented by formula (I):

11. A pharmaceutical composition, which comprises the compound represented by formula (I) according to claim 10 or a salt thereof, and a pharmaceutically acceptable carrier.