Nerve regeneration promoters containing semaphorin inhibitor as the active ingredient

• US 20070015820A1
• Filed: 08/24/2006
• Published: 01/18/2007
• Est. Priority Date: 07/28/2000
• Status: Active Grant

• Current Assignee: Dainippon Sumitomo Pharma Company Limited (Sumitomo Chemical Company Limited)
• Original Assignee: Dainippon Sumitomo Pharma Company Limited (Sumitomo Chemical Company Limited)
• Inventors: Kimura, Toru, Hosotani, Nobuo, Kumagai, Kazuo, Kishino, Akiyoshi, Kikuchi, Kaoru
• Granted Patent: US 7,317,038 B2
• Time in Patent Office: Days
• US Class Current: 514/455
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 311/78 Ring systems having three or more relevant rings
• CPC Class Codes: C07D 311/86 Oxygen atoms, e.g. xanthones
• CPC Class Codes: C07D 493/04 Ortho-condensed systems

Abstract

To provide a semaphorin inhibitor; a peripheral or central nerve regeneration promoter which contains said semaphorin inhibitor as an active ingredient; and a preventive or remedy for a neuropathic disease and a neurodegenerative disease containing said nerve regeneration promoter, or the like.

A low-molecular weight compound, which acts at a concentration of 10 μg/ml or below to inhibit the growth cone collapse activity of semaphorin such as semaphorin 3A, semaphorin 6C or the like and/or the nerve outgrowth inhibitory activity of semaphorin in a collagen gel and which does not substantially affect cell proliferation, is obtained from the culture of strain SPF-3059 belonging to the genus Penicillium. The low-molecular weight compound with the semaphorin inhibitory activity thus obtained exhibits the in vivo nerve-regeneration promoting action.

Claims

1-40. -40. (canceled)

41. A compound represented by formula [13], wherein at least one of R¹, R² and R⁵ represents a hydrogen atom, a pharmaceutically acceptable salt thereof or a derivative thereof,

42. The compound according to claim 41 wherein at least one of R² and R⁵ represents a hydroxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

43. The compound according to claim 42 wherein R² represents a hydroxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

44. The compound according to claim 42 wherein R² and R⁵ represent a hydroxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

45. The compound according to claim 41 wherein R⁴ represents a carboxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

46. The compound according to claim 41 wherein R² represents a hydroxyl group and R⁴ represents a carboxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

47. The compound according to claim 41 wherein R¹ and R⁴ represent a carboxyl group and R⁵ represents a hydroxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

91. The compound according to claim 42 wherein R⁴ represents a carboxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

92. The compound according to claim 43 wherein R⁴ represents a carboxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

93. The compound according to claim 44 wherein R⁴ represents a carboxyl group, a pharmaceutically acceptable salt thereof or a derivative thereof.

48-80. -80. (canceled)

81. A nerve regeneration promoter containing a compound represented by formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof, as an active ingredient,

82. The nerve regeneration promoter according to claim 81 wherein at least one of R² and R⁵ represents a hydroxyl group in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.

83. The semaphorin inhibitor according to claim 82 wherein R² represents a hydroxyl group in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.

84. The semaphorin inhibitor according to claim 82 wherein R² and R⁵ represent a hydroxyl group in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.

85. The semaphorin inhibitor according to claim 81 wherein R⁴ represents a carboxyl group in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.

86. The semaphorin inhibitor according to claim 82 wherein R⁴ represents a carboxyl group in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.

87. The semaphorin inhibitor according to claim 83 wherein R⁴ represents a carboxyl group in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.

88. The semaphorin inhibitor according to claim 84 wherein R⁴ represents a carboxyl group in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.

89. The semaphorin inhibitor according to claim 81 wherein R² and R⁵ represent a hydroxyl group, R¹ represents a carboxyl group and R⁴ represents a hydrogen atom in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.

90. The semaphorin inhibitor according to claim 81 wherein R¹ and R⁴ represent a carboxyl group and R⁵ represents a hydroxyl group in formula [13], a pharmaceutically acceptable salt thereof or a derivative thereof.