Claims
- 1. A nitrogen-containing tricyclic compound represented by the following formula (I), a hydrate thereof or a pharmacologically acceptable salt thereof: wherein R1, R2, R3, R4, R5, R6, R7 and R8 are the same or different from each other and each represents hydrogen, hydroxy, cyano, nitro, optionally substituted carbamoyl halogeno, optionally halogenated lower alkyl, optionally substituted cycloalkyl, optionally halogenated lower alkoxy, acyl, optionally protected carboxyl, optionally substituted aryl, optionally substituted heteroaryl, cycloalkylalkyl, hydroxylated alkyl, alkoxyalkyl, optionally protected carboxyalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, cyanoalkyl, acylalkyl, optionally substituted carbamoylalkyl, optionally halogenated alkenyl, hydroxyalkenyl, alkoxyalkenyl, optionally protected carboxyalkenyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, cyanoalkenyl, acylalkenyl, optionally substituted carbamoylalkenyl, optionally halogenated alkynyl, hydroxyalkynyl, alkoxyalkynyl, optionally protected carboxyalkynyl, optionally substituted arylalkynyl, optionally substituted heteroarylalkynyl, cyanoalkynyl, acylalkynyl, optionally substituted carbamoyalkynyl, hydroxyalkoxy, alkoxyalkoxy, optionally protected carboxyalkoxy, optionally substituted arylalkoxy, optionally substituted heteroarylalkoxy, —A—NR9R10, wherein A represents optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene or a single bond; and R9 and R10 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl, optionally substituted aryl or acyl, or R9 and R10 may form together with the nitrogen atom to which they are bonded a ring optionally having additional nitrogen, oxygen or sulfur, or wherein B represents optionally substituted alkylene, optionally substituted alkenylene; optionally substituted alkynylene or a single bond; R11 represents optionally halogenated lower alkyl or amino optionally substituted by lower alkyl; and x represents an integer of from 0 to 2; provided that two of R1, R2, R3, R4, R5, R6, R7, and R8 adjacent to each other may form together with the carbon atom to which they are bonded a ring optionally containing oxygen, sulfur or nitrogen and optionally substituted; Z represents wherein R12, R13 and R14 are the same or different from each other and each represents hydrogen, optionally substituted carbamoyl, optionally halogenated lower alkyl, optionally substituted cycloalkyl, acyl, optionally halogenated lower alkylsulfonyl, optionally substituted arylsulfonyl, optionally protected carboxyl, optionally substituted aryl, optionally substituted heteroaryl, cycloalkylalkyl, hydroxylated alkyl, alkoxyalkyl, optionally protected carboxyalkyl, optionally substituted arylakyl, optionally substituted heteroarylalkyl, cyanoalkyl, acylalkyl, optionally substituted carbamoylalkyl, optionally halogenated alkenyl, hydroxyalkenyl, alkoxyalkenyl, optionally protected carboxyalkenyl, optionally substituted arylalkenyl, optionally substituted heteroarylalkenyl, cyanoalkenyl, acylalkenyl, optionally substituted carbamoyalkenyl, optionally halogenated alkynyl, hydroxyalkynyl, alkoxyalkynyl, optionally protected carboxyalkynyl, optionally substituted arylalkynyl, optionally substituted heteroarylalkynyl, cyanoalkynyl, acylalkynyl, optionally substituted carbamoylalkynyl, —W—NR18R19, wherein W represents optionally branched alkylene, optionally branched alkenylene, optionally branched alkynylene or a single bond; R18 and R19 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl or acyl, or R18 and R19 may form together with the nitrogen atom to which they are bonded a ring optionally containing additional nitrogen, oxygen or sulfur; D represents optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene or wherein m and l are each an integer of from 0 to 6; the ring A means an optionally substituted hydrocarbon ring or an optionally substituted heterocycle; and Q represents optionally substituted carbamoyl, acyl, acylalkyl, optionally protected carboxyl, optionally substituted heteroaryl, or —NR20R21, wherein R20 and R21 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl, optionally halogenated lower alkoxy, hydroxylated alkyl, alkoxyalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted arylalkoxy, optionally substituted heteroaryloxy, optionally substituted heteroarylalkoxy, optionally protected carboxyalkyl, acyl, optionally substituted acylalkyl, optionally substituted acylamino, optionally substituted acylaminoalkyl, optionally substituted carbamoylalkyl, optionally substituted aminoalkyl, cyanoalkyl, acylalkyl, cycloalkyl, cycloalkylalkyl or amindino optionally substituted by lower alkyl, or R20 and R21 may form together with the nitrogen atom to which they are bonded an optionally substituted 3- to 8-membered ring which may have, as its ring-member other than carbon, at least one member selected from the group consisting of nitrogen, sulfur, oxygen and —NR22, wherein R22 represents hydrogen, optionally halogenated lower alkyl, acyl, optionally substituted acylalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl or —S(O)s—(Y)u—R23, wherein R23 represents hydrogen, optionally halogenated lower alkyl or optionally substituted aryl; Y represents methylene; s is an integer of from 0 to 2; and u is 0 or 1, provided that the following compound is excluded: the compound where R5 and R6 are both hydrogen atoms.
- 2. A nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein neither R5 nor R6 is hydrogen.
- 3. The nitrogen-containing tricyclic compound as set forth in any of claims 1 or 2, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein Z is
- 4. The nitrogen-containing tricyclic compound as set forth in any of claims 1 or 2, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein Z is
- 5. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R1, R2, R3,R4, R5, R6, R7 and R8 are the same or different from each other and each represents hydrogen, hydroxy, cyano, optionally substituted carbamoyl, halogeno, optionally halogenated lower alkyl, optionally substituted cycloalkyl, optionally halogenated lower alkoxy, acyl, optionally protected carboxyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxylated alkyl, alkoxyalkyl, optionally protected carboxyalkyl, or —A—NR9R10 (wherein A represents optionally substituted alkylene or a single bond; and R9 and R10 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl, or acyl).
- 6. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein Q represents —NR20R21, wherein R20 and R21 are the same or different from each other and each represents hydrogen, lower alkyl, lower alkoxy, hydroxylated alkyl, alkoxyalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkoxy, optionally protected carboxyalkyl, acyl, optionally substituted acylamino, optionally substituted acylaminoalkyl, optionally substituted aminoalkyl, cyanoalkyl, acylalkyl, cycloalkyl or cycloalkylalkyl, or R20 and R21 may form together with the nitrogen atom to which they are bonded an optionally substituted 3- to 8-membered ring which may have, as its ring-member other than carbon, furthermore, nitrogen, sulfur, oxygen or —NR22, wherein R22 represents hydrogen, optionally halogenated lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl or —S(O)s—(Y)u—R23, wherein R23 represents hydrogen, optionally halogenated lower alkyl or optionally substituted aryl; Y represents methylene; s is 0 or an integer of 1 or 2; and u is 0 or 1, or may be condensed with an optionally substituted benzene ring.
- 7. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein Q is —NR20R21, wherein:i) R20 and R21 are the same or different from each other and each represents hydrogen, lower alkyl, hydroxylated alkyl, alkoxyalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally protected carboxyalkyl, cyanoalkyl or cycloalkylalkyl; ii) R20 and R21 may form together with the nitrogen atom to which they are bonded an optionally substituted 5- to 6-membered ring which may have, as its ring-member other than carbon, at least one member selected from the group consisting of sulfur, oxygen or —NR22, wherein R22 represents hydrogen, optionally halogenated lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl or —S(O)s—(Y)u—R23, wherein R23 represents hydrogen, lower alkyl or optionally substituted aryl; Y represents methylene; s is an integer of from 0 or 2; and u is 0 or 1; or iii) the ring formed by R20, R21 and the nitrogen atom to which they are bonded is tetrahydroquinoline, tetrahydroisoquinoline, indoline or isoindoline.
- 8. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R5 and R6 are each lower alkyl.
- 9. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R1, R2, R3, R4, R7 and R8 are each hydrogen; R5 and R6 are each lower alkyl; and Z is
- 10. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R1, R2, R3, R4, R7 and R8 are each hydrogen; R5 and R6 are each lower alkyl; and Z is
- 11. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R5 and R6 are the same or different from each other and each represents methyl or ethyl.
- 12. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R5 and R6 are each methyl.
- 13. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R1, R2, R3, R4, R7 and R8 are the same or different from each other and each represents hydrogen, cyano, optionally substituted carbamoyl, halogeno, optionally halogenated lower alkyl, optionally substituted cycloalkyl, optionally halogenated lower alkoxy, acyl, optionally protected carboxyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyalkyl, alkoxyalkyl, optionally protected carboxyalkyl, or —A—NR9R10, wherein A represents optionally substituted alkylene, or a single bond; and R9 and R10 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl or acyl; R5 and R6 are each methyl; and z is
- 14. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R1, R2, R3, R4, R7 and R8 are the same or different from each other and each represents hydrogen, cyano, optionally substituted carbamoyl, halogeno, optionally halogenated lower alkyl, optionally substituted cycloalkyl, optionally halogenated lower alkoxy, acyl, optionally protected carboxyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyalkyl, alkoxyalkyl, optionally protected carboxyalkyl, or —A—NR9R10, wherein A represents optionally substituted alkylene, or a single bond; and R9 and R10 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl or acyl; R5 and R6 are each methyl; and z is
- 15. The nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof, wherein R12 represents optionally halogenated lower alkyl, optionally protected carboxyalkyl, cyanoalkyl, optionally substituted carbamoylalkyl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl.
- 16. A pharmaceutical composition containing a pharmacologically effective amount of the nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof together with pharmacologically acceptable carriers.
- 17. The composition as set forth in claim 16, which is a tyrosine kinase inhibitor, wherein the inhibitor is an antiallergic agent effective in treating asthma, allergic rhinitis, atopic dermatitis, hay fever, allergic conjunctivitis and food allergy.
- 18. A method for treating diseases which are treated by inhibiting the binding of the IgE receptor γ chain to a tyrosine kinase of 72 kDa which comprises administering a pharmacologically effective amount of the nitrogen-containing tricyclic compound as set forth in claim 1, a hydrate thereof or a pharmacologically acceptable salt thereof to a patient.
- 19. The method as set forth in claim 18 for treating diseases caused by chemical mediators selected from the group consisting of serotonin, histamine and leukotrienes.
- 20. The method as set forth in claim 18 for treating allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, urticaria, hay fever, gastrointestinal allergy or food allergy.
- 21. The method as set forth in claim 18 which comprises administering from about 0.03 to 1,000 mg/day of the active ingredient to an adult patient.
- 22. The method as set forth in claim 18 which comprises administering from 1 μg/kg to 3,000 μg/kg of the active ingredient as an injection to an adult patient.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 8-55628 |
Mar 1996 |
JP |
|
Parent Case Info
This application is a divisional of application Ser. No. 09/125,451, filed on Sep. 21, 1998, now U.S. Pat. No. 6,333,322, and for which priority is claimed under 35 U.S.C. § 120. application Ser. No. 09/125,451 is the national phase of PCT International application Ser. No. PCT/JP97/00789 filed on Mar. 13, 1997 under 35 U.S.C. § 371. The entire contents of each of the above-identified applications are hereby incorporated by reference. This application also claims priority of Application No. 8-055628 filed in Japan on Mar. 13, 1996 under 35 U.S.C. § 119.
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Patent Grant
6489336
