Patent EA-001899-B1 (EA)
Title: Pyrazolopyridine derivatives and pharmaceutical use thereof
Inventor: AKAHANE ATSUSHI
IPC: A61P3/10
Filed: 1997-07-17
Abstract: 1. A pyrazolopyridine derivatives of the following formula (I):   wherein R<1> is aryl, and R<2> is (C1-C6)alkyl substituted with unsaturated 3 to 8-membered heteromonocyclic group containing 1 or 2 sulfur atom(s) and 1 to 3 nitrogen atom(s) which may have one or more (C1-C6)alkyl substituent(s); a group of the formula:   wherein R<3> is hydrogen, (C1-C6)alkyl, ar(C1-C6)alkyl or acyl, R<4> is hydrogen or hydroxy, A is (C1-C6)alkylene, m is an integer of 0 or 1, and n is an integer of 1 or 2]; a group of the formula:   [wherein R<5> and R<6> are each (C1-C6)alkyl]; or quinuclidinyl, or a salt thereof. 2. A compound of Claim 1, wherein R<1> is phenyl, and R<2> is (C1-C6) alkyl substituted with thiazolyl which may have 1 to 3 (C1-C6) alkyl; a group of the formula:   [wherein R<3> is hydrogen, (C1-C6) alkyl, phenyl(C1-C6)alkyl, (C1-C6)alkanoyl, (C1-C6) alkoxycarbonyl, or phenyl(C1-C6)alkoxycarbonyl, R<4> is hydrogen or hydroxy, A is (C1-C6) alkylene, m is an integer of 0 or 1, and n is an integer of 1 or 2]; a group of the formula:   [wherein R<5> and R<6> are each (C1-C6) alkyl]; or quinuclidinyl, or a salt thereof. 3. A compound of Claim 2, wherein R<2> is (C1-C6) alkyl substituted with thiazolyl which may have 1 to 3 (C1-C6) alkyl, or a salt thereof. 4. A compound of Claim 2, wherein R<2> is a group of the formula:   [wherein R<3> is hydrogen, (C1-C6) alkyl, phenyl(C1-C6)alkyl, (C1-C6) alkanoyl, (C1-C6) alkoxycarbonyl, or phenyl(C1-C6)alkoxycarbonyl, R<4> is hydrogen or hydroxy, A is (C1-C6) alkylene, m is an integer of 0 or 1, and n is an integer of 1 or 2], or a salt thereof. 5. A compound of Claim 4, wherein R<2> is a group of the formula:   [wherein R<3> is hydrogen, (C1-C6) alkyl, phenyl(C1-C6)alkyl, (C1-C6) alkanoyl, or (C1-C6) alkoxycarbonyl, R<4> is hydrogen, A is (C1-C6) alkylene, m is an integer of 0, and n is an integer of 1 or 2], or a salt thereof. 6. A compound of Claim 5, wherein R<2> is a group of the formula:   [wherein R<3> is hydrogen, (C1-C6) alkyl, phenyl(C1-C6)alkyl, (C1-C6) alkanoyl, or (C1-C6) alkoxycarbonyl, R<4> is hydrogen, A is (C1-C6) alkylene, m is an integer of 0, and n is an integer of 2], or a salt thereof. 7. A compound of Claim 6, wherein R<2> is a group of the formula:   [wherein R<3> is (C1-C6) alkyl, R<4> is hydrogen, A is (C1-C6) alkylene, m is an integer of 0, and n is an integer of 2], or a salt thereof. 8. A compound of Claim 4, wherein R<2> is a group of the formula:   [wherein R<3> is hydrogen, (C1-C6) alkyl, (C1-C6) alkanoyl, or phenyl(C1-C6))alkoxycarbonyl, R<4> is hydrogen or hydroxy, A is (C1-C6) alkylene, m is an integer of 1, and n is an integer of 1 or 2], or a salt thereof. 9. A compound of Claim 8, wherein R<2> is a group of the formula:   [wherein R<3> is hydrogen, or (C1-C6) alkyl, R<4> is hydrogen, A is (C1-C6) alkylene, m is an integer of 1, and n is an integer of 1 or 2], or a salt thereof. 10. A process for the preparation of the pyrazolopyridine compound of Claim 1 or a salt thereof, which comprises reacting a compound of the formula (II):   wherein R<1> is as defined in Claim 1, or a salt thereof, with a compound of the formula (III): ( X-R<2> (III) wherein R<2> is as defined in Claim 1 and X is a leaving group, to give a compound of the formula (I):   wherein R<1> and R<2> are each as defined in Claim 1, or a salt thereof, and if desired, a compound of the formula (I), which is a compound of the formula (Ib):   wherein R<1> is as defined in Claim 1, and R<2b> is a group of the formula:   wherein A, m, n and R<4> are each as defined in Claim 1, and R<3a> is acyl, or a salt thereof, are put into reaction to eliminate acyl group, to give a compound of the formula (Ic):   wherein R<1> is as defined in Claim 1 and R<2c> is a group of the formula:   wherein A, m, n and R<4> are each as defined above, R<3b> is hydrogen, or a salt thereof, or a compound of the formula (I) which is a compound of the formula (Id):   wherein R<1> is as defined in Claim 1 and R<2d> is a group of the formula:   wherein A, m, n and R<4> are each as defined above and R<3c> is (C1-C6) alkyl, or a salt thereof, are put into dealkylation reaction, to give a compound of the formula (Ic):   wherein R<1> and R<2c> are each as defined above, or a salt thereof, or a compound of the formula (I), which is a compound of the formula (Ic):   wherein R<1> and R<2c> are each as defined above, or a salt thereof, is put into alkylation reaction, to give a compound of the formula (Ie):   wherein R<1> is as defined in Claim 1 and R<2e> is a group of the formula:   wherein A, m, n, R<3c> and R<4> are each as defined above, or a group of the formula:   wherein R<5> and R<6> are each as defined in Claim 1, or a salt thereof, or a compound of the formula (I) which is a compound of the formula (Ic):   wherein R<1> and R<2c> are each as defined above, or a salt thereof, is put into acylation reaction, to give a compound of the formula (Ib):   wherein R<1> and R<2b> are each as defined above, or a salt thereof. 11. A process for the preparation of the pyrazolopyridine compound of Claim 1 or a salt thereof, which comprises reacting a compound of the formula (II):   wherein R<1> is as defined in Claim 1, or a salt thereof with a compound of the formula (IV):   wherein n is as defined in Claim 1, and R<3a> is acyl to give a compound of the formula (Ia):   wherein R<1> and R<3a> are each as defined above, or a salt thereof. 12. A process for the preparation of the pyrazolopyridine compound of Claim 1 or a salt thereof, characterised in that the compound of formula (V):   wherein R<1> and A are each as defined in Claim 1, or a salt thereof, are put into formation reaction of thiazole ring, to give a compound of the formula (If):   wherein R<1> and A are each as defined above, or a salt thereof. 13. A pharmaceutical composition comprising the compound of Claim 1 or a salt thereof in association with pharmaceutically acceptable carriers or excipients. 14. A method for preventing or treating diseases on which an adenosine antagonist is therapeutically effective, which comprises administering the compound of Claim 1 or a salt thereof to a human being or an animal. 15. Use of the compound of Claim 1 or a salt thereof as a medicament. 16. Use of the compound of Claim 1 or a salt thereof as an adenosine antagonist. 17. A process for preparing a pharmaceutical composition which comprises admixing the compound of Claim 1 or a salt thereof with pharmaceutically acceptable carriers or excipients. 18. Use of the compound of Claim 1 or a salt thereof for the production of a pharmaceutical composition for the therapy of diseases on which an adenosine antagonist is therapeutically effective.