Method for treating hypoxia

• US 4,914,094 A
• Filed: 03/21/1989
• Issued: 04/03/1990
• Est. Priority Date: 12/09/1985
• Status: Expired due to Fees

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Inventors: Osaki, Masaaki, Kikuchi, Tetsuro, Oshiro, Yasuo
• Primary Examiner(s): Rollins, John W.
• Application Number:
  US07/326,845
• Time in Patent Office: 378 Days
• Field of Search: 514/213, 514/222, 514/233, 514/231.5, 514/247, 514/299, 514/253, 514/224.4, 540/523, 544/1, 544/336, 544/363, 546/112, 546/114, 546/115
• US Class Current: 514/212.07
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole

Abstract

A method for curing and/or improving hypoxia characterized by administering a compound represented by the general formula (1), ##STR1## said compounds have been known in prior art literatures, for example, as carbostyril derivatives in Japanese Patent Kokai No. 54-160389 (1979), etc., as benzoxazine derivatives in Japanese Patent Kokai No. 59-70675 (1984), and as benzoazepine derivatives in Japanese Patent Kokai No. 57-193461 (1982), and they have been known as central nervous system controlling agents and antihistaminic agents.

The present invention was established on the basis of the findings that the compounds represented by the general formula (1) possess excellent pharmacological activities for curing and/or improving hypoxia and also possess excellent anti-oxidative activities, which could not have been anticipated from the disclosures in the prior art literatures.

Claims

1. A method for treating hypoxia comprising, administering to a host in need of said treatment a compound or salt thereof represented by formula (1), ##STR13## wherein R¹ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or a phenyl-lower alkyl group;

Z is a group of the formula ##STR14## in which R² is a hydrogen atom or a lower alkyl group; and

the bond indicated as is a single or double bond, a group of the formula --(CH₂)₃ --, a group of the formula --O--CH₂ -- or a group of the formula --S--CH₂ --;

R³ is a pyridyl group, or a phenyl group which may have 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkoxy group and a hydroxy group; and

a group of the formula ##STR15## is a group of the formula ##STR16## and A is a lower alkylene group;

provided that when a group of the formula ##STR17## is a group of the formula ##STR18## then Z is a group of the formula ##STR19## and at the same time R³ should be neither a pyridyl group nor a phenyl group having at least one hydroxy group as the substituent;

or when R³ is a pyridyl group, then Z is a group of the formula ##STR20##

2. The method according to claim 1, wherein R³ in the general formula (1) is a phenyl group which may have 1 to 3 substituents selected from the group consisting of a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ alkoxy group and a hydroxy group.

3. The method according to claim 2, wherein R³ in the general formula (1) is a phenyl group which may have 1 to 2 substituents selected from the group consisting of a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ alkoxy group and a hydroxy group.

4. The method according to claim 3, wherein Z in the general formula (1) is a group of the formula ##STR21## (wherein R² is a hydrogen atom or a C₁ -C₆ alkyl group;

and the bond indicated as is the same defined above).

5. The method according to claim 4, wherein R² in the general formula (1) is a hydrogen atom.

6. The method according to claim 3, wherein Z in the general formula (1) is a group of the formula --O--CH₂ --.

7. The method according to claim 3, wherein Z in the general formula (1) is a group of the formula --(CH₂)₃ -- or a group of the formula --S--CH₂ --.

8. The method according to claims 5, 6 or 7, wherein R¹ in the general formula (1) is a hydrogen atom or a C₁ -C₆ alkyl group.

9. The method according to claim 1, wherein R³ in the general formula (1) is a pyridyl group.

10. A method for treating hypoxia which comprises administering to a host in need thereof a 7-{3-[4-(4-Methylphenyl)-1-piperazinyl]propoxy}-3,4-dihydrocarbostyril or a salt thereof in an amount effective for said treatment.

11. A method for treating hypoxia which comprises administering to a host in need thereof a 6-{3-[4-(3-(Methylphenyl)-1-piperazinyl]propoxy}-2H-1,4-benzoxazin-3(4H)-one or a salt thereof in an amount effective for said treatment.

12. A method for treating hypoxia which comprises administering to a host in need thereof a 7-{3-[4-(3-Chlorophenyl)-1-piperazinyl]propoxy}-3,4-dihydrocarbostyril or a salt thereof in an amount effective for said treatment.

13. A method for treating hypoxia which comprises administering to a host in need thereof a 7-{3-[4-(3-Methylphenyl)-1,2,5,6-tetrahydro-1-pyridyl]propoxy}-3,4-dihydrocarbostyril or a salt thereof in an amount effective for said treatment.

14. A method for treating hypoxia which comprises administering to a host in need thereof a 6-{3-[4-(2,3-Dimethylphenyl)-1-piperazinyl]propoxy-}-2H-1,4-benzoazine-3(4H)-one or a salt thereof in an amount effective for said treatment.

15. A method for treating hypoxia which comprises administering to a host in need thereof a 7-{3-[4-(4-Chlorophenyl)-1-piperazinyl]propoxy}-3,4-dihydrocarbostyril or a salt thereof in an amount effective for said treatment.