Claims for Patent: 4,863,910

Summary for Patent: 4,863,910

Title:	Complexes of AZO compounds and/or their salts and an antitumor agent and a method for reducing the growth of tumors
Abstract:	A complex of an azo compound of the formula ##STR1## wherein R and R\' are selected from the group consisting of hydrogen, --COCR.sub.4.sup.3, --COCHR.sub.2.sup.4, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 CH.sub.2 R.sup.4)2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of chlorine, ##STR2## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3 ; R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR3## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenissolin, R.sup.3 is selected from the group consisting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2, R.sup.4 is the same as defined herein above, or their pharmaceutically acceptable metal salts, and an antitumor agent selected from the group consisting of nitrogen mustard, cyclophosphamid, thyothepa, 6-mercaptopurine, 5-fluoruracil, vinblastine, L-asparaginase and prednisolone and treatment of tumors and living tissue.
Inventor(s):	Takayanagi; Takeo (Yonkers, NY)
Assignee:
Application Number:	06/876,834
Patent Claims:	1. A complex of an azo compound of the formula wherein R and R' are selected from the group consisting of hydrogen, --COCR.sub.3.sup.4, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 CH.sub.2 R.sup.4).sub.2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of chlorine, ##STR32## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3 ; R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR33## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenissolin, R.sup.3 is selected from the group consiting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2, R.sup.4 is the same as defined hereinabove, or their pharmaceutically acceptable metal salts, and an antitumor agent selected from the group consisting of nitrogen mustard, cyclophosphamid, thyothepa, 6-mercaptopurine, 5-fluoruracil, vinblastine, L-asparaginase and prednisolone. 2. A complex of an azo compound of the formula ##STR34## wherein R and R' are selected from the group consisting of hydrogen, --COCR.sub.3.sup.4, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 CH.sub.2 R.sup.4).sub.2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of chlorine, ##STR35## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3 ; R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR36## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenissolin, R.sup.3 is selected from the group consisting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2, R.sup.4 is the same as defined hereinabove, or their pharmaceutically acceptable metal salts, and an antibiotic selected from the group consisting of chloramphenicol, streptomycia and penicillin. 3. A complex of an azo compound of the formula ##STR37## wherein R and R' are selected from the group consisting of hydrogen, --COCR.sub.3.sup.4, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 CH.sub.2 R.sup.4).sub.2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of chlorine, ##STR38## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3 ; R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR39## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenissolin, R.sup.3 is selected from the group consisting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2, R.sup.4 is the same as defined hereinabove, or their salts pharmaceutically acceptable metal, and a curative organic compound selected from the group consisting of pyoktanin (methylviolet), methylene blue and acriflavine. 4. A complex of an azo compound of the formula ##STR40## wherein R and R' are selected from the group consisting of hydrogen, --COCR.sub.3.sup.4, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 C.sub.2 R.sup.4).sub.2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of chlorine, ##STR41## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3 ; R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR42## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenisolin, R.sup.3 is selected from the group consisting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2, R.sup.4 is the same as defined hereinabove, or their salts pharmaceutically acceptable metal, and an organic compound selected from the group consisting of abscisinic acid, p-hydroxybenzoic acid, D-glucosamine and glucoside. 5. A complex of an azo compound of the formula ##STR43## wherein R and R' are selected from the group consisting of hydrogen, --COCR.sub.3.sup.4, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 CH.sub.2 R.sup.4).sub.2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of Cl, ##STR44## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3 ; R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR45## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenissolin, R.sup.3 is selected from the group consisting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2 and R.sup.4 is the same as defined hereinabove, or their salts pharmaceutically acceptable metal, and an antitumor agent selected from the group consisting of nitrogen mustard, cyclophosphamid, thyothepa, 6-mercaptopurine, 5-fluoruracil, vinblastine, L-asparaginase and prednisolone. 6. A complex of an azo compound of the formula ##STR46## wherein R and R' are selected from the group consisting of hydrogen, --COCR.sub.3.sup.4, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 CH.sub.2 R.sup.4).sub.2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of Cl, ##STR47## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3 ; R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR48## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenissolin, R.sup.3 is selected from the group consisting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2 and R.sup.4 is the same as defined hereinabove, or their pharmaceutically acceptable metal salts, and an antibiotic selected from the group consisting of chloramphenicol, streptomycia and penicillin. 7. A complex of an azo compound of the formula ##STR49## wherein R and R' are selected from the group consisting of hydrogen, --COCR.sub.3.sup.4, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 CH.sub.2 R.sup.4).sub.2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of Cl, ##STR50## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3, R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR51## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenissolin, R.sup.3 is selected from the group consisting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2 and R.sup.4 is the same as defined hereinabove, or their pharmaceutically acceptable metal salts, and a curative organic compound selected from the group consisting of pyoktanin (methylviolet), methylene blue and acriflavine. 8. A complex of an azo compound of the formula ##STR52## wherein R and R' are selected from the group consisting of hydrogen, --COCR.sub.3.sup.4, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --CO.sub.2 C.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sup.4, --(CH.sub.2 CH.sub.2 R.sup.4).sub.2, --CH.sub.2 CH.sub.2 OH, --CONHCH.sub.2 CH.sub.2 R.sup.4 and --CH.sub.2 CH.sub.2 OCOHN.sub.2, R.sup.4 is selected from the group consisting of Cl, ##STR53## --NHCO.sub.2 CH.sub.2 CH.sub.2 OH, --HNCO.sub.2 C.sub.2 H.sub.5, --NHOH, --NHCONHOH and --NHCH.sub.3 ; R.sup.1 and R.sup.2 are individually selected from the group consisting of ##STR54## --NHCH.sub.2 CH.sub.2 Cl, --NHCONHOH, --NHCO.sub.2 C.sub.2 H.sub.5, 6-mercapropurin, 5-fluoruracil and prenissolin, R.sup.3 is selected from the group consisting of hydrogen, --COCHR.sub.2.sup.4, --SO.sub.2 CH.sub.3, --COC.sub.2 H.sub.5, --CH.sub.2 CH.sub.2 R.sub.4 and --CONH.sub.2 and R.sup.4 is the same as defined hereinabove, or their pharmaceutically acceptable metal salts, and an organic compound selected from the group consisting of abscisinic acid, p-hydroxybenzoic acid, D-glucosamine and glucoside. 9. A method of reducing the growth of tumors in living tissue comprising the treatment thereof with an effective amount of the complex of claim 1. 10. A method of reducing the growth of tumors in living tissue comprising the treatment thereof with an effective amount of the complex of claim 2. 11. A method of reducing the growth of tumors in living tissue comprising the treatment thereof with an effective amount of the complex of claim 3. 12. A method of reducing the growth of tumors in living tissue comprisign the treatment thereof with an effective amount of the complex of claim 4. 13. A method of reducing the growth of tumors in living tissue comprising the treatment thereof with an effective amount of the complex of claim 5. 14. A method of reducing the growth of tumors in living tissue comprising the treatment thereof with an effective amount of the complex of claim 6. 15. A method of reducing the growth of tumors in living tissue comprising the treatment thereof with an effective amount of the complex of claim 7. 16. A method of reducing the growth of tumors in living tissue comprising the treatment thereof with an effective amount of the complex of claim 8.

Details for Patent 4,863,910

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2039-03-29