Title:
ヒストンデメチラーゼLSD1及び/又はLSD2の阻害剤としてのトラニルシプロミン誘導体
Document Type and Number:
Japanese Patent JP2013525318
Kind Code:
A
Abstract:
Tranylcypromine derivatives useful as therapeutic agents, particularly for the prevention and/or treatment of diseases and conditions associated with the activity of histone demethylases LSD1 and LSD2, such as the diseases characterized by deregulation of gene transcription, cell differentiation and proliferation, e.g. tumors, viral infections, are herein described. These compounds belong to the structural formula (I) wherein A and R3 are as defined in the specification. The invention also relates to the preparation of these compounds, as well as to compositions containing them and to therapeutic use thereof.
Inventors:
Saverio Minucci
Antonello Mai
Andrea Matevi
Antonello Mai
Andrea Matevi
Application Number:
JP2013505423A
Publication Date:
June 20, 2013
Filing Date:
April 15, 2011
Export Citation:
Assignee:
Universita Degli Studio Di Roma La Sapienza
Fondazione Jeo
Universita Degli Studio Di Pavia
Universita Degli Studio Di Milan
Fondazione Jeo
Universita Degli Studio Di Pavia
Universita Degli Studio Di Milan
International Classes:
C07C233/44; A61K31/167; A61K31/27; A61K31/381; A61P31/12; A61P35/00; A61P35/02; C07C231/12; C07C233/80; C07C259/06; C07C269/06; C07C271/22; C07C271/28; C07C273/18; C07C275/16; C07D333/60
Domestic Patent References:
| JP2004502670A | 2004-01-29 | |||
| JP2004502670A | 2004-01-29 |
Foreign References:
| WO2010043721A1 | 2010-04-22 | |||
| WO2010084160A1 | 2010-07-29 | |||
| WO2010143582A1 | 2010-12-16 | |||
| WO2011035941A1 | 2011-03-31 | |||
| WO2005007614A1 | 2005-01-27 | |||
| WO1994027947A1 | 1994-12-08 | |||
| US5773644A | 1998-06-30 | |||
| WO2008117175A2 | 2008-10-02 | |||
| WO2010043721A1 | 2010-04-22 | |||
| WO2010084160A1 | 2010-07-29 | |||
| WO2010143582A1 | 2010-12-16 | |||
| WO2011035941A1 | 2011-03-31 | |||
| WO2005007614A1 | 2005-01-27 | |||
| WO1994027947A1 | 1994-12-08 | |||
| US5773644A | 1998-06-30 | |||
| WO2008117175A2 | 2008-10-02 |
Other References:
JPN6015009341; ＧＯＯＤＥＮ，ＤＡＶＩＤ Ｍ．，ＥＴ ＡＬ．: '"Ｆａｃｉｌｅ ｓｙｎｔｈｅｓｉｓ ｏｆ ｓｕｂｓｔｉｔｕｔｅｄ ｔｒａｎｓ-２-ａｒｙｌｃｙｃｌｏｐｒｏｐｙｌａｍｉｎｅｉｎｈｉｂｉｔｏｒｓ ｏｆ ｔｈｅ ｈｕｍａｎ ｈｉｓｔｏｎｅ ｄｅｍｅｔｈｙ' ＢＩＯＯＲＧＡＮＩＣ ＆ ＭＥＤＩＣＩＮＡＬ ＣＨＥＭＩＳＴＲＹ ＬＥＴＴＥＲＳ ＶＯＬ．１８，ＮＯ．１０, 2008, ＰＰ．３０４７-３０５１
JPN5013005755; ＢＩＮＤＡ，ＣＬＡＵＤＩＡ，ＥＴ ＡＬ．: '"Ｂｉｏｃｈｅｍｉｃａｌ， Ｓｔｒｕｃｔｕｒａｌ， ａｎｄ Ｂｉｏｌｏｇｉｃａｌ Ｅｖａｌｕａｔｉｏｎ ｏｆ Ｔｒａｎｙｌｃｙｐｒｏｍｉｎｅ Ｄｅｒｉｖａｔｉｖｅｓ ａｓ Ｉｎｈｉｂｉｔｏ' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３２，ＮＯ．１９, 2010, ＰＰ．６８２７-６８３３
JPN6015009343; ＳＣＨＭＩＤＴ，ＤＡＷＮ Ｍ． Ｚ．，ＥＴ ＡＬ．: '"ｔｒａｎｓ-２-Ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐｙｌａｍｉｎｅ Ｉｓ ａ Ｍｅｃｈａｎｉｓｍ-Ｂａｓｅｄ Ｉｎａｃｔｉｖａｔｏｒ ｏｆ ｔｈｅ Ｈｉｓｔｏｎｅ Ｄｅｍｅｔｈｙｌａｓｅ ＬＳＤ１"' ＢＩＯＣＨＥＭＩＳＴＲＹ ＶＯＬ．４６，ＮＯ．１４, 2007, ＰＰ．４４０８-４４１６
JPN6015009345; ＣＵＬＨＡＮＥ， ＪＥＦＦＲＥＹ Ｃ．， ＥＴ ＡＬ．: '"Ｃｏｍｐａｒａｔｉｖｅ Ａｎａｌｙｓｉｓ ｏｆ Ｓｍａｌｌ Ｍｏｌｅｃｕｌｅｓ ａｎｄ Ｈｉｓｔｏｎｅ Ｓｕｂｓｔｒａｔｅ Ａｎａｌｏｇｕｅｓ ａｓ ＬＳＤ１ Ｌｙｓｉｎｅ Ｄｄｅｍｅｔｈｙｌａｓｅ' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３２，ＮＯ．９, 2010, ＰＰ．３１６４-３１７６
JPN6015009347; ＵＥＤＡ， ＲＩＥ，ＥＴ ＡＬ．: '"Ｉｄｅｎｔｉｆｉｃａｔｉｏｎ ｏｆ Ｃｅｌｌ-Ａｃｔｉｖｅ Ｌｙｓｉｎｅ Ｓｐｅｃｉｆｉｃ Ｄｅｍｅｔｈｙｌａｓｅ １-Ｓｅｌｅｃｔｉｖｅ Ｉｎｈｉｂｉｔｏｒｓ"' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３１，ＮＯ．４８, 2009, ＰＰ．１７５３６-１７５３７
JPN6015009341; ＧＯＯＤＥＮ，ＤＡＶＩＤ Ｍ．，ＥＴ ＡＬ．: '"Ｆａｃｉｌｅ ｓｙｎｔｈｅｓｉｓ ｏｆ ｓｕｂｓｔｉｔｕｔｅｄ ｔｒａｎｓ-２-ａｒｙｌｃｙｃｌｏｐｒｏｐｙｌａｍｉｎｅｉｎｈｉｂｉｔｏｒｓ ｏｆ ｔｈｅ ｈｕｍａｎ ｈｉｓｔｏｎｅ ｄｅｍｅｔｈｙ' ＢＩＯＯＲＧＡＮＩＣ ＆ ＭＥＤＩＣＩＮＡＬ ＣＨＥＭＩＳＴＲＹ ＬＥＴＴＥＲＳ ＶＯＬ．１８，ＮＯ．１０, 2008, ＰＰ．３０４７-３０５１
JPN5013005755; ＢＩＮＤＡ，ＣＬＡＵＤＩＡ，ＥＴ ＡＬ．: '"Ｂｉｏｃｈｅｍｉｃａｌ， Ｓｔｒｕｃｔｕｒａｌ， ａｎｄ Ｂｉｏｌｏｇｉｃａｌ Ｅｖａｌｕａｔｉｏｎ ｏｆ Ｔｒａｎｙｌｃｙｐｒｏｍｉｎｅ Ｄｅｒｉｖａｔｉｖｅｓ ａｓ Ｉｎｈｉｂｉｔｏ' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３２，ＮＯ．１９, 2010, ＰＰ．６８２７-６８３３
JPN6015009343; ＳＣＨＭＩＤＴ，ＤＡＷＮ Ｍ． Ｚ．，ＥＴ ＡＬ．: '"ｔｒａｎｓ-２-Ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐｙｌａｍｉｎｅ Ｉｓ ａ Ｍｅｃｈａｎｉｓｍ-Ｂａｓｅｄ Ｉｎａｃｔｉｖａｔｏｒ ｏｆ ｔｈｅ Ｈｉｓｔｏｎｅ Ｄｅｍｅｔｈｙｌａｓｅ ＬＳＤ１"' ＢＩＯＣＨＥＭＩＳＴＲＹ ＶＯＬ．４６，ＮＯ．１４, 2007, ＰＰ．４４０８-４４１６
JPN6015009345; ＣＵＬＨＡＮＥ， ＪＥＦＦＲＥＹ Ｃ．， ＥＴ ＡＬ．: '"Ｃｏｍｐａｒａｔｉｖｅ Ａｎａｌｙｓｉｓ ｏｆ Ｓｍａｌｌ Ｍｏｌｅｃｕｌｅｓ ａｎｄ Ｈｉｓｔｏｎｅ Ｓｕｂｓｔｒａｔｅ Ａｎａｌｏｇｕｅｓ ａｓ ＬＳＤ１ Ｌｙｓｉｎｅ Ｄｄｅｍｅｔｈｙｌａｓｅ' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３２，ＮＯ．９, 2010, ＰＰ．３１６４-３１７６
JPN6015009347; ＵＥＤＡ， ＲＩＥ，ＥＴ ＡＬ．: '"Ｉｄｅｎｔｉｆｉｃａｔｉｏｎ ｏｆ Ｃｅｌｌ-Ａｃｔｉｖｅ Ｌｙｓｉｎｅ Ｓｐｅｃｉｆｉｃ Ｄｅｍｅｔｈｙｌａｓｅ １-Ｓｅｌｅｃｔｉｖｅ Ｉｎｈｉｂｉｔｏｒｓ"' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３１，ＮＯ．４８, 2009, ＰＰ．１７５３６-１７５３７
JPN5013005755; ＢＩＮＤＡ，ＣＬＡＵＤＩＡ，ＥＴ ＡＬ．: '"Ｂｉｏｃｈｅｍｉｃａｌ， Ｓｔｒｕｃｔｕｒａｌ， ａｎｄ Ｂｉｏｌｏｇｉｃａｌ Ｅｖａｌｕａｔｉｏｎ ｏｆ Ｔｒａｎｙｌｃｙｐｒｏｍｉｎｅ Ｄｅｒｉｖａｔｉｖｅｓ ａｓ Ｉｎｈｉｂｉｔｏ' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３２，ＮＯ．１９, 2010, ＰＰ．６８２７-６８３３
JPN6015009343; ＳＣＨＭＩＤＴ，ＤＡＷＮ Ｍ． Ｚ．，ＥＴ ＡＬ．: '"ｔｒａｎｓ-２-Ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐｙｌａｍｉｎｅ Ｉｓ ａ Ｍｅｃｈａｎｉｓｍ-Ｂａｓｅｄ Ｉｎａｃｔｉｖａｔｏｒ ｏｆ ｔｈｅ Ｈｉｓｔｏｎｅ Ｄｅｍｅｔｈｙｌａｓｅ ＬＳＤ１"' ＢＩＯＣＨＥＭＩＳＴＲＹ ＶＯＬ．４６，ＮＯ．１４, 2007, ＰＰ．４４０８-４４１６
JPN6015009345; ＣＵＬＨＡＮＥ， ＪＥＦＦＲＥＹ Ｃ．， ＥＴ ＡＬ．: '"Ｃｏｍｐａｒａｔｉｖｅ Ａｎａｌｙｓｉｓ ｏｆ Ｓｍａｌｌ Ｍｏｌｅｃｕｌｅｓ ａｎｄ Ｈｉｓｔｏｎｅ Ｓｕｂｓｔｒａｔｅ Ａｎａｌｏｇｕｅｓ ａｓ ＬＳＤ１ Ｌｙｓｉｎｅ Ｄｄｅｍｅｔｈｙｌａｓｅ' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３２，ＮＯ．９, 2010, ＰＰ．３１６４-３１７６
JPN6015009347; ＵＥＤＡ， ＲＩＥ，ＥＴ ＡＬ．: '"Ｉｄｅｎｔｉｆｉｃａｔｉｏｎ ｏｆ Ｃｅｌｌ-Ａｃｔｉｖｅ Ｌｙｓｉｎｅ Ｓｐｅｃｉｆｉｃ Ｄｅｍｅｔｈｙｌａｓｅ １-Ｓｅｌｅｃｔｉｖｅ Ｉｎｈｉｂｉｔｏｒｓ"' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３１，ＮＯ．４８, 2009, ＰＰ．１７５３６-１７５３７
JPN6015009341; ＧＯＯＤＥＮ，ＤＡＶＩＤ Ｍ．，ＥＴ ＡＬ．: '"Ｆａｃｉｌｅ ｓｙｎｔｈｅｓｉｓ ｏｆ ｓｕｂｓｔｉｔｕｔｅｄ ｔｒａｎｓ-２-ａｒｙｌｃｙｃｌｏｐｒｏｐｙｌａｍｉｎｅｉｎｈｉｂｉｔｏｒｓ ｏｆ ｔｈｅ ｈｕｍａｎ ｈｉｓｔｏｎｅ ｄｅｍｅｔｈｙ' ＢＩＯＯＲＧＡＮＩＣ ＆ ＭＥＤＩＣＩＮＡＬ ＣＨＥＭＩＳＴＲＹ ＬＥＴＴＥＲＳ ＶＯＬ．１８，ＮＯ．１０, 2008, ＰＰ．３０４７-３０５１
JPN5013005755; ＢＩＮＤＡ，ＣＬＡＵＤＩＡ，ＥＴ ＡＬ．: '"Ｂｉｏｃｈｅｍｉｃａｌ， Ｓｔｒｕｃｔｕｒａｌ， ａｎｄ Ｂｉｏｌｏｇｉｃａｌ Ｅｖａｌｕａｔｉｏｎ ｏｆ Ｔｒａｎｙｌｃｙｐｒｏｍｉｎｅ Ｄｅｒｉｖａｔｉｖｅｓ ａｓ Ｉｎｈｉｂｉｔｏ' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３２，ＮＯ．１９, 2010, ＰＰ．６８２７-６８３３
JPN6015009343; ＳＣＨＭＩＤＴ，ＤＡＷＮ Ｍ． Ｚ．，ＥＴ ＡＬ．: '"ｔｒａｎｓ-２-Ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐｙｌａｍｉｎｅ Ｉｓ ａ Ｍｅｃｈａｎｉｓｍ-Ｂａｓｅｄ Ｉｎａｃｔｉｖａｔｏｒ ｏｆ ｔｈｅ Ｈｉｓｔｏｎｅ Ｄｅｍｅｔｈｙｌａｓｅ ＬＳＤ１"' ＢＩＯＣＨＥＭＩＳＴＲＹ ＶＯＬ．４６，ＮＯ．１４, 2007, ＰＰ．４４０８-４４１６
JPN6015009345; ＣＵＬＨＡＮＥ， ＪＥＦＦＲＥＹ Ｃ．， ＥＴ ＡＬ．: '"Ｃｏｍｐａｒａｔｉｖｅ Ａｎａｌｙｓｉｓ ｏｆ Ｓｍａｌｌ Ｍｏｌｅｃｕｌｅｓ ａｎｄ Ｈｉｓｔｏｎｅ Ｓｕｂｓｔｒａｔｅ Ａｎａｌｏｇｕｅｓ ａｓ ＬＳＤ１ Ｌｙｓｉｎｅ Ｄｄｅｍｅｔｈｙｌａｓｅ' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３２，ＮＯ．９, 2010, ＰＰ．３１６４-３１７６
JPN6015009347; ＵＥＤＡ， ＲＩＥ，ＥＴ ＡＬ．: '"Ｉｄｅｎｔｉｆｉｃａｔｉｏｎ ｏｆ Ｃｅｌｌ-Ａｃｔｉｖｅ Ｌｙｓｉｎｅ Ｓｐｅｃｉｆｉｃ Ｄｅｍｅｔｈｙｌａｓｅ １-Ｓｅｌｅｃｔｉｖｅ Ｉｎｈｉｂｉｔｏｒｓ"' ＪＯＵＲＮＡＬ ＯＦ ＴＨＥ ＡＭＥＲＩＣＡＮ ＣＨＥＭＩＣＡＬ ＳＯＣＩＥＴＹ ＶＯＬ．１３１，ＮＯ．４８, 2009, ＰＰ．１７５３６-１７５３７
Attorney, Agent or Firm:
Yasuhiko Murayama
Masatake Shiga
Takashi Watanabe
Shinya Mitsuhiro
Masatake Shiga
Takashi Watanabe
Shinya Mitsuhiro