Angiogenesis Inhibitor Containing Amine Derivative as Active Ingredient

• US 20090253765A1
• Filed: 05/17/2006
• Published: 10/08/2009
• Est. Priority Date: 05/17/2005
• Status: Abandoned Application

• Current Assignee: Santen Pharmaceutical Company Limited
• Original Assignee: Santen Pharmaceutical Company Limited
• Inventors: Doi, Reina, Kurose, Tatsuji, Oohashi, Kouji, Kageyama, Masaaki
• Application Number:
  US11/920,607
• Publication Number:
  US 20090253765A1
• Time in Patent Office: Days
• US Class Current: 514/398
• CPC Class Codes: A61K 31/235 having an aromatic ring attached to a carboxyl group
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

An object of the present invention is to provide an angiogenesis inhibitor. The angiogenesis inhibitor according to the present invention contains a compound represented by the following general formula [I] or a salt thereof as an active ingredient. In the formula, the ring A represents a benzene ring or a naphthalene ring; X represents a single bond, an alkylene group or —CH₂COOCH₂—; Y represents an oxygen atom or N(R₆); R₁, R₂ and R₃ are the same or different and represent a hydrogen atom or an alkyl group, or R₁ and R₃ may be joined together to form a ring having one or more double bonds; R₄ and R₅ are the same or different and represent a hydrogen atom or an alkyl group; and R₆ represents a hydrogen atom or an alkyl group.

Claims

1. An angiogenesis inhibitor comprising as an active ingredient a compound represented by the following general formula [I] or a salt thereof:

wherein the ring A represents a benzene ring or a naphthalene ring;

X represents a single bond, an alkylene group or —

CH₂COOCH₂—

;

Y represents an oxygen atom or N(R₆);

R₁, R₂ and R₃ are the same or different and represent a hydrogen atom or an alkyl group, or R₁ and R₃ may be joined together to form a ring having one or more double bonds;

R₄ and R₅ are the same or different and represent a hydrogen atom or an alkyl group; and

R₆ represents a hydrogen atom or an alkyl group.

2. The angiogenesis inhibitor according to claim 1 comprising as an active ingredient a compound represented by the following general formula [II] or a salt thereof:

wherein R₁, R₂ and R₃ are the same or different and represent a hydrogen atom or an alkyl group, or R₁ and R₃ may be joined together to form a ring having one or more double bonds.

3. The angiogenesis inhibitor according to claim 1, wherein the compound represented by the general formula [I] is 6′

-amidino-2′

-naphthyl-4-guanidinobenzoate, 6′

-amidino-2′

-naphthyl-(4-(4,5-dihydro-1H-2-imidazolyl)amino)benzoate or N,N-dimethylcarbamoylmethyl-4-(4-guanidinobenzoyloxy)phenylacetate.

7. The angiogenesis inhibitor according to claim 1, wherein the dosage form is an oral preparation, an injection, an eye drop, or a preparation for intraocular implant.

4. A preventive or therapeutic agent for a disease accompanied by angiogenesis, comprising as an active ingredient a compound represented by the following general formula [I] or a salt thereof:

wherein the ring A represents a benzene ring or a naphthalene ring;

X represents a single bond, an alkylene group or —

CH₂COOCH₂—

;

Y represents an oxygen atom or N(R₆);

R₁, R₂ and R₃ are the same or different and represent a hydrogen atom or an alkyl group, or R₁ and R₃ may be joined together to form a ring having one or more double bonds;

R₄ and R₅ are the same or different and represent a hydrogen atom or an alkyl group; and

R₆ represents a hydrogen atom or an alkyl group.

5. The preventive or therapeutic agent according to claim 4, wherein the disease accompanied by angiogenesis is an ophthalmic disease.

6. The preventive or therapeutic agent according to claim 5, wherein the ophthalmic disease is diabetic retinopathy, retinopathy of prematurity, macular degeneration, neovascular glaucoma, retinal vein occlusion, retinal artery occlusion, pterygium, rubeosis or pannus.

8. A method for inhibiting angiogenesis comprising administering to a patient a pharmacologically effective amount of a compound represented by the following general formula [I] or a salt thereof:

wherein the ring A represents a benzene ring or a naphthalene ring;

X represents a single bond, an alkylene group or —

CH₂COOCH₂—

;

Y represents an oxygen atom or N(R₆);

R₁, R₂ and R₃ are the same or different and represent a hydrogen atom or an alkyl group, or R₁ and R₃ may be joined together to form a ring having one or more double bonds;

R₄ and R₅ are the same or different and represent a hydrogen atom or an alkyl group; and

R₆ represents a hydrogen atom or an alkyl group.

10. The method for inhibiting angiogenesis according to claim 8, wherein the compound represented by the general formula [I] is 6′

-amidino-2′

-naphthyl-4-guanidinobenzoate, 6′

-amidino-2′

-naphthyl-(4-(4,5-dihydro-1H-2-imidazolyl)amino)benzoate or N,N-dimethylcarbamoylmethyl-4-(4-guanidinobenzoyloxy)phenylacetate.

14. The method for inhibiting angiogenesis according to claim 8, wherein the administration is carried out using an oral preparation, an injection, an eye drop, or a preparation for intraocular implant.

23. The method for inhibiting angiogenesis according to claim 10, wherein the administration is carried out using an oral preparation, an injection, an eye drop, or a preparation for intraocular implant.

9. A method for inhibiting angiogenesis comprising administering to a patient a pharmacologically effective amount of a compound represented by the following general formula [II] or a salt thereof:

wherein R₁, R₂ and R₃ are the same or different and represent a hydrogen atom or an alkyl group, or R₁ and R₃ may be joined together to form a ring having one or more double bonds.

22. The method for inhibiting angiogenesis according to claim 9, wherein the administration is carried out using an oral preparation, an injection, an eye drop, or a preparation for intraocular implant.

11. A method for preventing or treating a disease accompanied by angiogenesis comprising administering to a patient a pharmacologically effective amount of a compound represented by the following general formula [I] or a salt thereof:

wherein the ring A represents a benzene ring or a naphthalene ring;

X represents a single bond, an alkylene group or —

CH₂COOCH₂—

;

Y represents an oxygen atom or N(R₆);

R₁, R₂ and R₃ are the same or different and represent a hydrogen atom or an alkyl group, or R₁ and R₃ may be joined together to form a ring having one or more double bonds;

R₄ and R₅ are the same or different and represent a hydrogen atom or an alkyl group; and

R₆ represents a hydrogen atom or an alkyl group.

12. The method for preventing or treating according to claim 11, wherein the disease accompanied by angiogenesis is an ophthalmic disease.

13. The method for preventing or treating according to claim 12, wherein the ophthalmic disease is diabetic retinopathy, retinopathy of prematurity, macular degeneration, neovascular glaucoma, retinal vein occlusion, retinal artery occlusion, pterygium, rubeosis or pannus.

24. The method for preventing or treating according to claim 11, wherein the administration is carried out using an oral preparation, an injection, an eye drop, or a preparation for intraocular implant.

25. The method for preventing or treating according to claim 12, wherein the administration is carried out using an oral preparation, an injection, an eye drop, or a preparation for intraocular implant.

26. The method for preventing or treating according to claim 13, wherein the administration is carried out using an oral preparation, an injection, an eye drop, or a preparation for intraocular implant.

27. The method for preventing or treating according to claim 12, wherein the compound represented by the general formula [1] is a compound represented by the following general formula [II] or a salt thereof:

wherein R₁, R₂ and R₃ are the same or different and represent a hydrogen atom or an alkyl group, or R₁ and R₃ may be joined together to form a ring having one or more double bonds.

28. The method for preventing or treating according to claim 12, wherein the compound represented by the general formula [1] is 6′

-amidino-2′

-naphthyl-4-guanidinobenzoate, 6′

-amidino-2′

-naphthyl-(4-(4,5-dihydro-1H-2-imidazolyl)amino)benzoate or N,N-dimethylcarbamoylmethyl-4-(4-guanidinobenzoyloxy)phenylacetate.

15-21. -21. (canceled)