Title:
【発明の名称】アポトーシスにより誘導される自己免疫疾患を処置するためのベンゾジアゼピンの使用
Document Type and Number:
Japanese Patent JP2002543121
Kind Code:
A
Abstract:
Benzodiazepine compounds, and methods for using those compounds are provided. Some of the benzodiazepine compounds include 1,4-benzodiazepine-2-one and 1.4-benzodiazepine-2,5-dione compounds of structures (I) or (II): wherein R 1 , R 2 , R 3 and R 4 are as defined. The invention also includes enantiomers, pharmaceutically acceptable salts, prodrugs or derivatives of the benzodiazepine compounds. Any one or more of these benzodiazepine compounds can be used to treat a variety of dysregulatory disorders related to cellular death. Such disorders include autoimmune disorders, inflammatory conditions, hyperproliferative conditions, viral infections, and atherosclerosis. In addition, the above compounds can be used to prepare medicaments to treat the above-described dysregulatory disorders. The benzodiazepines can also be used in drugs screening assays and other diagnostic methods.
Inventors:
Glick, Garry Dee.
Opipari, Anthony W. Jr.
Opipari, Anthony W. Jr.
Application Number:
JP2000614991A
Publication Date:
December 17, 2002
Filing Date:
April 27, 2000
Export Citation:
Assignee:
The Regents of the University of Michigan
International Classes:
A61K31/551; A61K31/5513; A61K45/00; A61P1/00; A61P9/10; A61P11/06; A61P15/00; A61P17/06; A61P19/02; A61P19/04; A61P21/04; A61P29/00; A61P31/12; A61P31/18; A61P31/22; A61P35/00; A61P37/00; A61P37/02; A61P37/06; C07D243/14; C07D243/24; C07D401/12; C07D403/12; C07D413/12; (IPC1-7): C07D243/14; A61K31/5513; A61K45/00; A61P1/00; A61P9/10; A61P11/06; A61P15/00; A61P17/06; A61P19/02; A61P19/04; A61P21/04; A61P29/00; A61P31/12; A61P31/18; A61P31/22; A61P35/00; A61P37/02; A61P37/06; C07D243/24; C07D401/12; C07D403/12; C07D413/12
Foreign References:
| US4898861A | 1990-02-06 | |||
| US3374264A | 1968-03-19 | |||
| DE1810423A1 | 1969-10-09 | |||
| US3374264A | 1968-03-19 | |||
| DE1810423A1 | 1969-10-09 | |||
| US4898861A | 1990-02-06 |
Other References:
JPN6010074938; Ｍ． Ａｋｓｓｉｒａ ｅｔ ａｌ．: 'Ｎｅｗ Ｒｏｕｔｅｓ ｔｏ １，４-ｂｅｎｚｏｄｉａｚｅｐｉｎ-２，５-ｄｉｏｎｅｓ' Ｔｅｔｒａｈｅｄｒｏｎ Ｖｏｌ．５０， Ｎｏ．３０, 1994, ｐ．９０５１-９０６０
JPN6010074939; Ｇ． Ｍｏｈｉｕｄｄｉｎ ｅｔ ａｌ．: 'Ａ Ｖｅｒｓａｔｉｌｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ ３Ｈ-１（Ｈ），４（Ｈ）-Ｂｅｎｚｏｄｉａｚｅｐｉｎ-２，５-ｄｉｏｎｅｓ' Ｉｎｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．２４Ｂ, 1985, ｐ．９０５-９０７
JPN6010074940; Ｃｏｎｓｔａｎｔｉｎｅ Ｇ． Ｂｏｏｊａｍｒａ ｅｔ ａｌ．: 'Ａｎ Ｅｘｐｅｄｉｅｎｔ ａｎｄ Ｈｉｇｈ-Ｙｉｅｌｄｉｎｇ Ｍｅｔｈｏｄ ｆｏｒ ｔｈｅ Ｓｏｌｉｄ-Ｐｈａｓｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ Ｄｉｖｅｒｓｅ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６０， Ｎｏ．１８, 1995, ｐ．５７４２-５７４３
JPN6010074941; Ｔｈｏｍａｓ Ａ． Ｋｅａｔｉｎｇ ｅｔ ａｌ．: 'Ａ Ｒｅｍａｒｋａｂｌｅ Ｔｗｏ-Ｓｔｅｐ Ｓｙｎｔｈｅｓｉｓ ｏｆ Ｄｉｖｅｒｓｅ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，５-ｄｉｏｎｅｓ Ｕｓｉｎｇ ｔｈｅ Ｕｇｉ Ｆｏｕｒ-Ｃｏｍｐｏｎｅｎ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６１， Ｎｏ．２５, 1996, ｐ．８９３５-８９３９
JPN6010074942; Ｅｕｓｅｂｉｏ Ｊｕａｒｉｓｔｉ ｅｔ ａｌ．: 'Ｅｎａｎｔｉｏｓｅｌｅｃｔｉｖｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ alpha-Ａｍｉｎｏ Ａｃｉｄｓ ｆｒｏｍ Ｃｈｉｒａｌ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，５-ｄｉｏｎｅｓ Ｃｏｎｔａｉｎｉｎｇ ｔｈ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６４， Ｎｏ．８, 19990326, ｐ．２９１４-２９１８
JPN6010074943; Ｇａｓｐｅｒ Ｍａｒｃ ｅｔ ａｌ．: 'Ｈｉｇｈ Ｙｉｅｌｄ Ｐｈａｓｅ Ｔｒａｎｓｆｅｒ Ｎ-Ａｌｋｙｌａｔｉｏｎ ｏｆ Ｓｏｍｅ Ｂｅｎｚｏｄｉａｚｅｐｉｎｅｓ ｂｙ Ｅｓｔｅｒｓ ｏｆ omega-Ｈａｌｏ Ａｃｉｄｓ' Ｓｙｎｔｈｅｔｉｃ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ Ｖｏｌ．２８， Ｎｏ．７, 1998, ｐ．１１４３-１１５７
JPN6010074938; Ｍ． Ａｋｓｓｉｒａ ｅｔ ａｌ．: 'Ｎｅｗ Ｒｏｕｔｅｓ ｔｏ １，４-ｂｅｎｚｏｄｉａｚｅｐｉｎ-２，５-ｄｉｏｎｅｓ' Ｔｅｔｒａｈｅｄｒｏｎ Ｖｏｌ．５０， Ｎｏ．３０, 1994, ｐ．９０５１-９０６０
JPN6010074939; Ｇ． Ｍｏｈｉｕｄｄｉｎ ｅｔ ａｌ．: 'Ａ Ｖｅｒｓａｔｉｌｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ ３Ｈ-１（Ｈ），４（Ｈ）-Ｂｅｎｚｏｄｉａｚｅｐｉｎ-２，５-ｄｉｏｎｅｓ' Ｉｎｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．２４Ｂ, 1985, ｐ．９０５-９０７
JPN6010074940; Ｃｏｎｓｔａｎｔｉｎｅ Ｇ． Ｂｏｏｊａｍｒａ ｅｔ ａｌ．: 'Ａｎ Ｅｘｐｅｄｉｅｎｔ ａｎｄ Ｈｉｇｈ-Ｙｉｅｌｄｉｎｇ Ｍｅｔｈｏｄ ｆｏｒ ｔｈｅ Ｓｏｌｉｄ-Ｐｈａｓｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ Ｄｉｖｅｒｓｅ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６０， Ｎｏ．１８, 1995, ｐ．５７４２-５７４３
JPN6010074941; Ｔｈｏｍａｓ Ａ． Ｋｅａｔｉｎｇ ｅｔ ａｌ．: 'Ａ Ｒｅｍａｒｋａｂｌｅ Ｔｗｏ-Ｓｔｅｐ Ｓｙｎｔｈｅｓｉｓ ｏｆ Ｄｉｖｅｒｓｅ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，５-ｄｉｏｎｅｓ Ｕｓｉｎｇ ｔｈｅ Ｕｇｉ Ｆｏｕｒ-Ｃｏｍｐｏｎｅｎ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６１， Ｎｏ．２５, 1996, ｐ．８９３５-８９３９
JPN6010074942; Ｅｕｓｅｂｉｏ Ｊｕａｒｉｓｔｉ ｅｔ ａｌ．: 'Ｅｎａｎｔｉｏｓｅｌｅｃｔｉｖｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ alpha-Ａｍｉｎｏ Ａｃｉｄｓ ｆｒｏｍ Ｃｈｉｒａｌ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，５-ｄｉｏｎｅｓ Ｃｏｎｔａｉｎｉｎｇ ｔｈ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６４， Ｎｏ．８, 19990326, ｐ．２９１４-２９１８
JPN6010074943; Ｇａｓｐｅｒ Ｍａｒｃ ｅｔ ａｌ．: 'Ｈｉｇｈ Ｙｉｅｌｄ Ｐｈａｓｅ Ｔｒａｎｓｆｅｒ Ｎ-Ａｌｋｙｌａｔｉｏｎ ｏｆ Ｓｏｍｅ Ｂｅｎｚｏｄｉａｚｅｐｉｎｅｓ ｂｙ Ｅｓｔｅｒｓ ｏｆ omega-Ｈａｌｏ Ａｃｉｄｓ' Ｓｙｎｔｈｅｔｉｃ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ Ｖｏｌ．２８， Ｎｏ．７, 1998, ｐ．１１４３-１１５７
JPN6010074939; Ｇ． Ｍｏｈｉｕｄｄｉｎ ｅｔ ａｌ．: 'Ａ Ｖｅｒｓａｔｉｌｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ ３Ｈ-１（Ｈ），４（Ｈ）-Ｂｅｎｚｏｄｉａｚｅｐｉｎ-２，５-ｄｉｏｎｅｓ' Ｉｎｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．２４Ｂ, 1985, ｐ．９０５-９０７
JPN6010074940; Ｃｏｎｓｔａｎｔｉｎｅ Ｇ． Ｂｏｏｊａｍｒａ ｅｔ ａｌ．: 'Ａｎ Ｅｘｐｅｄｉｅｎｔ ａｎｄ Ｈｉｇｈ-Ｙｉｅｌｄｉｎｇ Ｍｅｔｈｏｄ ｆｏｒ ｔｈｅ Ｓｏｌｉｄ-Ｐｈａｓｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ Ｄｉｖｅｒｓｅ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６０， Ｎｏ．１８, 1995, ｐ．５７４２-５７４３
JPN6010074941; Ｔｈｏｍａｓ Ａ． Ｋｅａｔｉｎｇ ｅｔ ａｌ．: 'Ａ Ｒｅｍａｒｋａｂｌｅ Ｔｗｏ-Ｓｔｅｐ Ｓｙｎｔｈｅｓｉｓ ｏｆ Ｄｉｖｅｒｓｅ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，５-ｄｉｏｎｅｓ Ｕｓｉｎｇ ｔｈｅ Ｕｇｉ Ｆｏｕｒ-Ｃｏｍｐｏｎｅｎ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６１， Ｎｏ．２５, 1996, ｐ．８９３５-８９３９
JPN6010074942; Ｅｕｓｅｂｉｏ Ｊｕａｒｉｓｔｉ ｅｔ ａｌ．: 'Ｅｎａｎｔｉｏｓｅｌｅｃｔｉｖｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ alpha-Ａｍｉｎｏ Ａｃｉｄｓ ｆｒｏｍ Ｃｈｉｒａｌ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，５-ｄｉｏｎｅｓ Ｃｏｎｔａｉｎｉｎｇ ｔｈ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６４， Ｎｏ．８, 19990326, ｐ．２９１４-２９１８
JPN6010074943; Ｇａｓｐｅｒ Ｍａｒｃ ｅｔ ａｌ．: 'Ｈｉｇｈ Ｙｉｅｌｄ Ｐｈａｓｅ Ｔｒａｎｓｆｅｒ Ｎ-Ａｌｋｙｌａｔｉｏｎ ｏｆ Ｓｏｍｅ Ｂｅｎｚｏｄｉａｚｅｐｉｎｅｓ ｂｙ Ｅｓｔｅｒｓ ｏｆ omega-Ｈａｌｏ Ａｃｉｄｓ' Ｓｙｎｔｈｅｔｉｃ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ Ｖｏｌ．２８， Ｎｏ．７, 1998, ｐ．１１４３-１１５７
JPN6010074938; Ｍ． Ａｋｓｓｉｒａ ｅｔ ａｌ．: 'Ｎｅｗ Ｒｏｕｔｅｓ ｔｏ １，４-ｂｅｎｚｏｄｉａｚｅｐｉｎ-２，５-ｄｉｏｎｅｓ' Ｔｅｔｒａｈｅｄｒｏｎ Ｖｏｌ．５０， Ｎｏ．３０, 1994, ｐ．９０５１-９０６０
JPN6010074939; Ｇ． Ｍｏｈｉｕｄｄｉｎ ｅｔ ａｌ．: 'Ａ Ｖｅｒｓａｔｉｌｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ ３Ｈ-１（Ｈ），４（Ｈ）-Ｂｅｎｚｏｄｉａｚｅｐｉｎ-２，５-ｄｉｏｎｅｓ' Ｉｎｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．２４Ｂ, 1985, ｐ．９０５-９０７
JPN6010074940; Ｃｏｎｓｔａｎｔｉｎｅ Ｇ． Ｂｏｏｊａｍｒａ ｅｔ ａｌ．: 'Ａｎ Ｅｘｐｅｄｉｅｎｔ ａｎｄ Ｈｉｇｈ-Ｙｉｅｌｄｉｎｇ Ｍｅｔｈｏｄ ｆｏｒ ｔｈｅ Ｓｏｌｉｄ-Ｐｈａｓｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ Ｄｉｖｅｒｓｅ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６０， Ｎｏ．１８, 1995, ｐ．５７４２-５７４３
JPN6010074941; Ｔｈｏｍａｓ Ａ． Ｋｅａｔｉｎｇ ｅｔ ａｌ．: 'Ａ Ｒｅｍａｒｋａｂｌｅ Ｔｗｏ-Ｓｔｅｐ Ｓｙｎｔｈｅｓｉｓ ｏｆ Ｄｉｖｅｒｓｅ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，５-ｄｉｏｎｅｓ Ｕｓｉｎｇ ｔｈｅ Ｕｇｉ Ｆｏｕｒ-Ｃｏｍｐｏｎｅｎ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６１， Ｎｏ．２５, 1996, ｐ．８９３５-８９３９
JPN6010074942; Ｅｕｓｅｂｉｏ Ｊｕａｒｉｓｔｉ ｅｔ ａｌ．: 'Ｅｎａｎｔｉｏｓｅｌｅｃｔｉｖｅ Ｓｙｎｔｈｅｓｉｓ ｏｆ alpha-Ａｍｉｎｏ Ａｃｉｄｓ ｆｒｏｍ Ｃｈｉｒａｌ １，４-Ｂｅｎｚｏｄｉａｚｅｐｉｎｅ-２，５-ｄｉｏｎｅｓ Ｃｏｎｔａｉｎｉｎｇ ｔｈ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．６４， Ｎｏ．８, 19990326, ｐ．２９１４-２９１８
JPN6010074943; Ｇａｓｐｅｒ Ｍａｒｃ ｅｔ ａｌ．: 'Ｈｉｇｈ Ｙｉｅｌｄ Ｐｈａｓｅ Ｔｒａｎｓｆｅｒ Ｎ-Ａｌｋｙｌａｔｉｏｎ ｏｆ Ｓｏｍｅ Ｂｅｎｚｏｄｉａｚｅｐｉｎｅｓ ｂｙ Ｅｓｔｅｒｓ ｏｆ omega-Ｈａｌｏ Ａｃｉｄｓ' Ｓｙｎｔｈｅｔｉｃ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ Ｖｏｌ．２８， Ｎｏ．７, 1998, ｐ．１１４３-１１５７
Attorney, Agent or Firm:
Shusaku Yamamoto