Title:
ジペプチジルペプチダーゼ-IV(DPP-IV)の阻害薬としての医薬組成物
Document Type and Number:
Japanese Patent JP2009508815
Kind Code:
A
Abstract:
The present invention relates to compounds, which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II, as well as hyperglycemia, metabolic syndrome, hyperinsulinemia, obesity, atherosclerosis, various immunomodulatory diseases, and other diseases.
Inventors:
Pay, Chiyonhua
Bon Geldern, Thomas
Madder, David The Ray
Li, Sheaofen
Basiya, Juaythema
Yong, Hong
Long Netker, Kenton El
Vazquez, Bratzley Jay
Jayad, Andrew S
Malhan, Machine M
Stewart, Kent Day
Bon Geldern, Thomas
Madder, David The Ray
Li, Sheaofen
Basiya, Juaythema
Yong, Hong
Long Netker, Kenton El
Vazquez, Bratzley Jay
Jayad, Andrew S
Malhan, Machine M
Stewart, Kent Day
Application Number:
JP2008529179A
Publication Date:
March 05, 2009
Filing Date:
August 25, 2006
Export Citation:
Assignee:
ABBOTT LABORATORIES
International Classes:
C07C211/40; A61K31/135; A61K31/136; A61K31/137; A61K31/165; A61K31/167; A61K31/195; A61K31/196; A61K31/277; A61K31/357; A61K31/36; A61K31/381; A61K31/401; A61K31/4035; A61K31/404; A61K31/423; A61K31/426; A61K31/4355; A61K31/437; A61K31/4402; A61K31/4418; A61K31/444; A61K31/445; A61K31/4453; A61K31/455; A61K31/472; A61K31/495; A61K31/496; A61K31/4985; A61K31/506; A61K31/5375; A61P1/02; A61P1/04; A61P3/00; A61P3/04; A61P3/10; A61P9/00; A61P9/10; A61P11/00; A61P15/12; A61P19/00; A61P19/10; A61P21/00; A61P25/00; A61P25/18; A61P25/20; A61P25/22; A61P25/24; A61P25/28; A61P29/00; A61P35/00; A61P37/02; A61P43/00; C07C211/48; C07C211/52; C07C217/52; C07C217/62; C07C217/84; C07C225/22; C07C229/42; C07C229/46; C07C229/48; C07C229/60; C07C233/43; C07C235/46; C07C237/24; C07C237/30; C07C255/58; C07C317/22; C07C317/36; C07D207/16; C07D209/08; C07D209/48; C07D211/46; C07D211/60; C07D211/62; C07D213/38; C07D213/63; C07D213/74; C07D213/82; C07D217/04; C07D263/56; C07D277/04; C07D295/12; C07D295/18; C07D295/20; C07D317/58; C07D317/66; C07D319/18; C07D333/40; C07D409/04; C07D487/04; C07D491/056; C07D513/04; C07B57/00
Domestic Patent References:
| JPH08505847A | 1996-06-25 | |||
| JPS63501217A | 1988-05-12 | |||
| JP2006508913A | 2006-03-16 | |||
| JP2000507256A | 2000-06-13 | |||
| JPH09512020A | 1997-12-02 | |||
| JP2008524279A | 2008-07-10 | |||
| JP2008503491A | 2008-02-07 | |||
| JP2008545691A | 2008-12-18 | |||
| JP2006508913A | 2006-03-16 | |||
| JP2000507256A | 2000-06-13 | |||
| JPH09512020A | 1997-12-02 | |||
| JP2008524279A | 2008-07-10 | |||
| JP2008503491A | 2008-02-07 | |||
| JP2008545691A | 2008-12-18 | |||
| JPH08505847A | 1996-06-25 | |||
| JPS63501217A | 1988-05-12 |
Foreign References:
| WO2005000406A2 | 2005-01-06 | |||
| GB1328935A | 1973-09-05 | |||
| WO1991011437A1 | 1991-08-08 | |||
| GB1328935A | 1973-09-05 | |||
| WO1991011437A1 | 1991-08-08 | |||
| WO2005000406A2 | 2005-01-06 |
Other References:
JPN5008013715; ＤＡＲＬＩＮＧ，Ｃ．Ｍ． ａｎｄ ＲＯＳＥ，Ｅ．Ｋ．: 'Ｓｙｎｔｈｅｓｉｓ ｏｆ ｈｉｓｔａｍｉｎｅ ａｎａｌｏｇｓ' ＪＯＵＲＮＡＬ ＯＦ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＳＣＩＥＮＣＥＳ Ｖ６５ Ｎ１, 1976, Ｐ９８-１０２
JPN5008013711; ＬＯＷＲＹ，Ｂ．Ｒ． ａｎｄ ＨＵＴＴＥＩＣ，Ａ．Ｃ．: 'Ｃｉｓ- ａｎｄ ｔｒａｎｓ-２-（３，４，５-Ｔｒｉｍｅｔｈｏｘｙｐｈｅｎｙｌ）ｃｙｃｌｏｈｅｘｙｌａｍｉｎｅｓ： Ｎ-Ｍｅｔｈｙｌ ａｎｄ Ｎ，Ｎ-ｄｉｍｅｔｈｙｌ ｄｅｒｉｖａｔｉｖｅｓ' ＪＯＵＲＮＡＬ ＯＦ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＳＣＩＥＮＣＥＳ Ｖ６０ Ｎ４, 197104, Ｐ６３２-６３３
JPN6012028769; ＦＵＬＬＥＲ，Ｒ．Ｗ． ｅｔ ａｌ．: 'Ｅｆｆｅｃｔ ｏｆ ｃｉｓ ａｎｄ ｔｒａｎｓ ｉｓｏｍｅｒｓ ｏｆ １-ａｍｉｎｏ-２-（ｐ-ｃｈｌｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｈｅｘａｎｅ， ｃｏｎｆｏｒｍａｔｉｏｎａｌｌｙ ｒｅｓｔｒ' Ｒｅｓｅａｒｃｈ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ ｉｎ Ｃｈｅｍｉｃａｌ Ｐａｔｈｏｌｏｇｙ ａｎｄ Ｐｈａｒｍａｃｏｌｏｇｙ ３８（２）, 1982, ３４９-５２
JPN6012028772; ＭＣＧＲＡＴＨ，Ｗ．Ｒ． ａｎｄ ＫＵＨＮ，Ｗ．Ｌ．: 'Ｐｈａｒｍａｃｏｌｏｇｉｃ ｅｆｆｅｃｔｓ ｏｆ ２-ｐｈｅｎｙｌｃｙｃｌｏａｌｋｙｌａｍｉｎｅｓ' Ａｒｃｈｉｖｅｓ Ｉｎｔｅｒｎａｔｉｏｎａｌｅｓ ｄｅ Ｐｈａｒｍａｃｏｄｙｎａｍｉｅ ｅｔ ｄｅ Ｔｈｅｒａｐｉｅ １７２（２）, 1968, ４０５-１３
JPN6012028774; ＫＵＳＴＥＲ，Ｇ．Ｊ． ａｎｄ ＳＣＨＥＥＲＥＮ，Ｈ．Ｗ．: 'Ｔｈｅ ｐｒｅｐａｒａｔｉｏｎ ｏｆ ｒｅｓｉｎ-ｂｏｕｎｄ ｎｉｔｒｏ ａｌｋｅｎｅｓ ａｎｄ ｓｏｍｅ ａｐｐｌｉｃａｔｉｏｎｓ ｉｎ ｈｉｇｈ-ｐｒｅｓｓｕｒｅ ｐｒｏｍｏｔｅｄ ｃｙｃｌｏａｄ' Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ ４１（４）, 2000, ５１５-５１９
JPN6012028780; ＨＥＮＤＲＩＣＫＳＯＮ，Ｊ．Ｂ． ｅｔ ａｌ．: 'Ａｐｐｒｏａｃｈｅｓ ｔｏ ｔｈｅ ｔｏｔａｌ ｓｙｎｔｈｅｓｉｓ ｏｆ ｌｙｃｏｒｉｎｅ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ３４（９）, 1969, ２６６７-７６
JPN6012028776; ＷＨＥＬＴＯＮ，Ｂ．Ｄ． ａｎｄ ＨＵＩＴＲＩＣ，Ａ．Ｃ．: 'Ｓｔｅｒｅｏｃｈｅｍｉｓｔｒｙ ｏｆ ａｍｉｄｏ ｄｅｒｉｖａｔｉｖｅｓ ｏｆ ３ａ，４，５，６-ｔｅｔｒａｈｙｄｒｏｉｎｄａｎ ａｎｄ ｒｅｌａｔｅｄ ｃｏｍｐｏｕｎｄｓ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ３７（１５）, 1972, ２３９６-９
JPN5008013710; ＤＡＳ，Ｐ．Ｃ． ｅｔ ａｌ．: 'Ｓｔｕｄｉｅｓ ｏｎ ｃｙｃｌｏａｌｋｙｌａｍｉｎｅ ｄｅｒｉｖａｔｉｖｅｓ' ＩＮＤＩＡＮ ＪＯＵＲＮＡＬ ＯＦ ＣＨＥＭＩＳＴＲＹ Ｖ１２ Ｎ１１, 197411, Ｐ１１３９-１１４０
JPN6012028778; ＧＩＢＳＯＮ，Ｍ．Ｓ．: '１０-Ｍｅｔｈｙｌｐｈｅｎａｎｔｈｒｉｄｉｎｅ' Ｊｏｕｒｎａｌ ｏｆ ｔｈｅ Ｃｈｅｍｉｃａｌ Ｓｏｃｉｅｔｙ , 1961, ２２４９-２２５１
JPN6012028782; ＡＲＵＭＵＧＡＭ，Ｎ． ａｎｄ ＳＨＥＮＢＡＧＡＭＵＲＴＨＩ，Ｐ．: 'Ｒｅａｃｔｉｏｎ ｏｆ １-Ａｒｙｌ-１-ｃｈｌｏｒｏ-２-ｎｉｔｒｏｓｏｃｙｃｌｏｈｅｘａｎｅｓ ｗｉｔｈ ＬＡＨ' Ｉｎｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ １３（８）, 1975, ８５７-８５８
JPN5008013714; ＰＯＮＯＭＡＲＥＶ，Ａ．Ａ．: ＭＥＴＯＤＹ ＰＯＬＵＣＨＥＮＩＹＡ ＫＨＩＭＩＣＨＥＳＫＩＫＨ ＲＥＡＫＴＩＶＯＶ Ｉ ＰＲＥＰＡＲＡＴＯＶ Ｎ１７, 1967, Ｐ１６５-１６６
JPN5008013715; ＤＡＲＬＩＮＧ，Ｃ．Ｍ． ａｎｄ ＲＯＳＥ，Ｅ．Ｋ．: 'Ｓｙｎｔｈｅｓｉｓ ｏｆ ｈｉｓｔａｍｉｎｅ ａｎａｌｏｇｓ' ＪＯＵＲＮＡＬ ＯＦ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＳＣＩＥＮＣＥＳ Ｖ６５ Ｎ１, 1976, Ｐ９８-１０２
JPN5008013711; ＬＯＷＲＹ，Ｂ．Ｒ． ａｎｄ ＨＵＴＴＥＩＣ，Ａ．Ｃ．: 'Ｃｉｓ- ａｎｄ ｔｒａｎｓ-２-（３，４，５-Ｔｒｉｍｅｔｈｏｘｙｐｈｅｎｙｌ）ｃｙｃｌｏｈｅｘｙｌａｍｉｎｅｓ： Ｎ-Ｍｅｔｈｙｌ ａｎｄ Ｎ，Ｎ-ｄｉｍｅｔｈｙｌ ｄｅｒｉｖａｔｉｖｅｓ' ＪＯＵＲＮＡＬ ＯＦ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＳＣＩＥＮＣＥＳ Ｖ６０ Ｎ４, 197104, Ｐ６３２-６３３
JPN6012028769; ＦＵＬＬＥＲ，Ｒ．Ｗ． ｅｔ ａｌ．: 'Ｅｆｆｅｃｔ ｏｆ ｃｉｓ ａｎｄ ｔｒａｎｓ ｉｓｏｍｅｒｓ ｏｆ １-ａｍｉｎｏ-２-（ｐ-ｃｈｌｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｈｅｘａｎｅ， ｃｏｎｆｏｒｍａｔｉｏｎａｌｌｙ ｒｅｓｔｒ' Ｒｅｓｅａｒｃｈ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ ｉｎ Ｃｈｅｍｉｃａｌ Ｐａｔｈｏｌｏｇｙ ａｎｄ Ｐｈａｒｍａｃｏｌｏｇｙ ３８（２）, 1982, ３４９-５２
JPN6012028772; ＭＣＧＲＡＴＨ，Ｗ．Ｒ． ａｎｄ ＫＵＨＮ，Ｗ．Ｌ．: 'Ｐｈａｒｍａｃｏｌｏｇｉｃ ｅｆｆｅｃｔｓ ｏｆ ２-ｐｈｅｎｙｌｃｙｃｌｏａｌｋｙｌａｍｉｎｅｓ' Ａｒｃｈｉｖｅｓ Ｉｎｔｅｒｎａｔｉｏｎａｌｅｓ ｄｅ Ｐｈａｒｍａｃｏｄｙｎａｍｉｅ ｅｔ ｄｅ Ｔｈｅｒａｐｉｅ １７２（２）, 1968, ４０５-１３
JPN6012028774; ＫＵＳＴＥＲ，Ｇ．Ｊ． ａｎｄ ＳＣＨＥＥＲＥＮ，Ｈ．Ｗ．: 'Ｔｈｅ ｐｒｅｐａｒａｔｉｏｎ ｏｆ ｒｅｓｉｎ-ｂｏｕｎｄ ｎｉｔｒｏ ａｌｋｅｎｅｓ ａｎｄ ｓｏｍｅ ａｐｐｌｉｃａｔｉｏｎｓ ｉｎ ｈｉｇｈ-ｐｒｅｓｓｕｒｅ ｐｒｏｍｏｔｅｄ ｃｙｃｌｏａｄ' Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ ４１（４）, 2000, ５１５-５１９
JPN6012028780; ＨＥＮＤＲＩＣＫＳＯＮ，Ｊ．Ｂ． ｅｔ ａｌ．: 'Ａｐｐｒｏａｃｈｅｓ ｔｏ ｔｈｅ ｔｏｔａｌ ｓｙｎｔｈｅｓｉｓ ｏｆ ｌｙｃｏｒｉｎｅ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ３４（９）, 1969, ２６６７-７６
JPN6012028776; ＷＨＥＬＴＯＮ，Ｂ．Ｄ． ａｎｄ ＨＵＩＴＲＩＣ，Ａ．Ｃ．: 'Ｓｔｅｒｅｏｃｈｅｍｉｓｔｒｙ ｏｆ ａｍｉｄｏ ｄｅｒｉｖａｔｉｖｅｓ ｏｆ ３ａ，４，５，６-ｔｅｔｒａｈｙｄｒｏｉｎｄａｎ ａｎｄ ｒｅｌａｔｅｄ ｃｏｍｐｏｕｎｄｓ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ３７（１５）, 1972, ２３９６-９
JPN5008013710; ＤＡＳ，Ｐ．Ｃ． ｅｔ ａｌ．: 'Ｓｔｕｄｉｅｓ ｏｎ ｃｙｃｌｏａｌｋｙｌａｍｉｎｅ ｄｅｒｉｖａｔｉｖｅｓ' ＩＮＤＩＡＮ ＪＯＵＲＮＡＬ ＯＦ ＣＨＥＭＩＳＴＲＹ Ｖ１２ Ｎ１１, 197411, Ｐ１１３９-１１４０
JPN6012028778; ＧＩＢＳＯＮ，Ｍ．Ｓ．: '１０-Ｍｅｔｈｙｌｐｈｅｎａｎｔｈｒｉｄｉｎｅ' Ｊｏｕｒｎａｌ ｏｆ ｔｈｅ Ｃｈｅｍｉｃａｌ Ｓｏｃｉｅｔｙ , 1961, ２２４９-２２５１
JPN6012028782; ＡＲＵＭＵＧＡＭ，Ｎ． ａｎｄ ＳＨＥＮＢＡＧＡＭＵＲＴＨＩ，Ｐ．: 'Ｒｅａｃｔｉｏｎ ｏｆ １-Ａｒｙｌ-１-ｃｈｌｏｒｏ-２-ｎｉｔｒｏｓｏｃｙｃｌｏｈｅｘａｎｅｓ ｗｉｔｈ ＬＡＨ' Ｉｎｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ １３（８）, 1975, ８５７-８５８
JPN5008013714; ＰＯＮＯＭＡＲＥＶ，Ａ．Ａ．: ＭＥＴＯＤＹ ＰＯＬＵＣＨＥＮＩＹＡ ＫＨＩＭＩＣＨＥＳＫＩＫＨ ＲＥＡＫＴＩＶＯＶ Ｉ ＰＲＥＰＡＲＡＴＯＶ Ｎ１７, 1967, Ｐ１６５-１６６
JPN5008013711; ＬＯＷＲＹ，Ｂ．Ｒ． ａｎｄ ＨＵＴＴＥＩＣ，Ａ．Ｃ．: 'Ｃｉｓ- ａｎｄ ｔｒａｎｓ-２-（３，４，５-Ｔｒｉｍｅｔｈｏｘｙｐｈｅｎｙｌ）ｃｙｃｌｏｈｅｘｙｌａｍｉｎｅｓ： Ｎ-Ｍｅｔｈｙｌ ａｎｄ Ｎ，Ｎ-ｄｉｍｅｔｈｙｌ ｄｅｒｉｖａｔｉｖｅｓ' ＪＯＵＲＮＡＬ ＯＦ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＳＣＩＥＮＣＥＳ Ｖ６０ Ｎ４, 197104, Ｐ６３２-６３３
JPN6012028769; ＦＵＬＬＥＲ，Ｒ．Ｗ． ｅｔ ａｌ．: 'Ｅｆｆｅｃｔ ｏｆ ｃｉｓ ａｎｄ ｔｒａｎｓ ｉｓｏｍｅｒｓ ｏｆ １-ａｍｉｎｏ-２-（ｐ-ｃｈｌｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｈｅｘａｎｅ， ｃｏｎｆｏｒｍａｔｉｏｎａｌｌｙ ｒｅｓｔｒ' Ｒｅｓｅａｒｃｈ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ ｉｎ Ｃｈｅｍｉｃａｌ Ｐａｔｈｏｌｏｇｙ ａｎｄ Ｐｈａｒｍａｃｏｌｏｇｙ ３８（２）, 1982, ３４９-５２
JPN6012028772; ＭＣＧＲＡＴＨ，Ｗ．Ｒ． ａｎｄ ＫＵＨＮ，Ｗ．Ｌ．: 'Ｐｈａｒｍａｃｏｌｏｇｉｃ ｅｆｆｅｃｔｓ ｏｆ ２-ｐｈｅｎｙｌｃｙｃｌｏａｌｋｙｌａｍｉｎｅｓ' Ａｒｃｈｉｖｅｓ Ｉｎｔｅｒｎａｔｉｏｎａｌｅｓ ｄｅ Ｐｈａｒｍａｃｏｄｙｎａｍｉｅ ｅｔ ｄｅ Ｔｈｅｒａｐｉｅ １７２（２）, 1968, ４０５-１３
JPN6012028774; ＫＵＳＴＥＲ，Ｇ．Ｊ． ａｎｄ ＳＣＨＥＥＲＥＮ，Ｈ．Ｗ．: 'Ｔｈｅ ｐｒｅｐａｒａｔｉｏｎ ｏｆ ｒｅｓｉｎ-ｂｏｕｎｄ ｎｉｔｒｏ ａｌｋｅｎｅｓ ａｎｄ ｓｏｍｅ ａｐｐｌｉｃａｔｉｏｎｓ ｉｎ ｈｉｇｈ-ｐｒｅｓｓｕｒｅ ｐｒｏｍｏｔｅｄ ｃｙｃｌｏａｄ' Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ ４１（４）, 2000, ５１５-５１９
JPN6012028780; ＨＥＮＤＲＩＣＫＳＯＮ，Ｊ．Ｂ． ｅｔ ａｌ．: 'Ａｐｐｒｏａｃｈｅｓ ｔｏ ｔｈｅ ｔｏｔａｌ ｓｙｎｔｈｅｓｉｓ ｏｆ ｌｙｃｏｒｉｎｅ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ３４（９）, 1969, ２６６７-７６
JPN6012028776; ＷＨＥＬＴＯＮ，Ｂ．Ｄ． ａｎｄ ＨＵＩＴＲＩＣ，Ａ．Ｃ．: 'Ｓｔｅｒｅｏｃｈｅｍｉｓｔｒｙ ｏｆ ａｍｉｄｏ ｄｅｒｉｖａｔｉｖｅｓ ｏｆ ３ａ，４，５，６-ｔｅｔｒａｈｙｄｒｏｉｎｄａｎ ａｎｄ ｒｅｌａｔｅｄ ｃｏｍｐｏｕｎｄｓ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ３７（１５）, 1972, ２３９６-９
JPN5008013710; ＤＡＳ，Ｐ．Ｃ． ｅｔ ａｌ．: 'Ｓｔｕｄｉｅｓ ｏｎ ｃｙｃｌｏａｌｋｙｌａｍｉｎｅ ｄｅｒｉｖａｔｉｖｅｓ' ＩＮＤＩＡＮ ＪＯＵＲＮＡＬ ＯＦ ＣＨＥＭＩＳＴＲＹ Ｖ１２ Ｎ１１, 197411, Ｐ１１３９-１１４０
JPN6012028778; ＧＩＢＳＯＮ，Ｍ．Ｓ．: '１０-Ｍｅｔｈｙｌｐｈｅｎａｎｔｈｒｉｄｉｎｅ' Ｊｏｕｒｎａｌ ｏｆ ｔｈｅ Ｃｈｅｍｉｃａｌ Ｓｏｃｉｅｔｙ , 1961, ２２４９-２２５１
JPN6012028782; ＡＲＵＭＵＧＡＭ，Ｎ． ａｎｄ ＳＨＥＮＢＡＧＡＭＵＲＴＨＩ，Ｐ．: 'Ｒｅａｃｔｉｏｎ ｏｆ １-Ａｒｙｌ-１-ｃｈｌｏｒｏ-２-ｎｉｔｒｏｓｏｃｙｃｌｏｈｅｘａｎｅｓ ｗｉｔｈ ＬＡＨ' Ｉｎｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ １３（８）, 1975, ８５７-８５８
JPN5008013714; ＰＯＮＯＭＡＲＥＶ，Ａ．Ａ．: ＭＥＴＯＤＹ ＰＯＬＵＣＨＥＮＩＹＡ ＫＨＩＭＩＣＨＥＳＫＩＫＨ ＲＥＡＫＴＩＶＯＶ Ｉ ＰＲＥＰＡＲＡＴＯＶ Ｎ１７, 1967, Ｐ１６５-１６６
JPN5008013715; ＤＡＲＬＩＮＧ，Ｃ．Ｍ． ａｎｄ ＲＯＳＥ，Ｅ．Ｋ．: 'Ｓｙｎｔｈｅｓｉｓ ｏｆ ｈｉｓｔａｍｉｎｅ ａｎａｌｏｇｓ' ＪＯＵＲＮＡＬ ＯＦ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＳＣＩＥＮＣＥＳ Ｖ６５ Ｎ１, 1976, Ｐ９８-１０２
JPN5008013711; ＬＯＷＲＹ，Ｂ．Ｒ． ａｎｄ ＨＵＴＴＥＩＣ，Ａ．Ｃ．: 'Ｃｉｓ- ａｎｄ ｔｒａｎｓ-２-（３，４，５-Ｔｒｉｍｅｔｈｏｘｙｐｈｅｎｙｌ）ｃｙｃｌｏｈｅｘｙｌａｍｉｎｅｓ： Ｎ-Ｍｅｔｈｙｌ ａｎｄ Ｎ，Ｎ-ｄｉｍｅｔｈｙｌ ｄｅｒｉｖａｔｉｖｅｓ' ＪＯＵＲＮＡＬ ＯＦ ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ ＳＣＩＥＮＣＥＳ Ｖ６０ Ｎ４, 197104, Ｐ６３２-６３３
JPN6012028769; ＦＵＬＬＥＲ，Ｒ．Ｗ． ｅｔ ａｌ．: 'Ｅｆｆｅｃｔ ｏｆ ｃｉｓ ａｎｄ ｔｒａｎｓ ｉｓｏｍｅｒｓ ｏｆ １-ａｍｉｎｏ-２-（ｐ-ｃｈｌｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｈｅｘａｎｅ， ｃｏｎｆｏｒｍａｔｉｏｎａｌｌｙ ｒｅｓｔｒ' Ｒｅｓｅａｒｃｈ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ ｉｎ Ｃｈｅｍｉｃａｌ Ｐａｔｈｏｌｏｇｙ ａｎｄ Ｐｈａｒｍａｃｏｌｏｇｙ ３８（２）, 1982, ３４９-５２
JPN6012028772; ＭＣＧＲＡＴＨ，Ｗ．Ｒ． ａｎｄ ＫＵＨＮ，Ｗ．Ｌ．: 'Ｐｈａｒｍａｃｏｌｏｇｉｃ ｅｆｆｅｃｔｓ ｏｆ ２-ｐｈｅｎｙｌｃｙｃｌｏａｌｋｙｌａｍｉｎｅｓ' Ａｒｃｈｉｖｅｓ Ｉｎｔｅｒｎａｔｉｏｎａｌｅｓ ｄｅ Ｐｈａｒｍａｃｏｄｙｎａｍｉｅ ｅｔ ｄｅ Ｔｈｅｒａｐｉｅ １７２（２）, 1968, ４０５-１３
JPN6012028774; ＫＵＳＴＥＲ，Ｇ．Ｊ． ａｎｄ ＳＣＨＥＥＲＥＮ，Ｈ．Ｗ．: 'Ｔｈｅ ｐｒｅｐａｒａｔｉｏｎ ｏｆ ｒｅｓｉｎ-ｂｏｕｎｄ ｎｉｔｒｏ ａｌｋｅｎｅｓ ａｎｄ ｓｏｍｅ ａｐｐｌｉｃａｔｉｏｎｓ ｉｎ ｈｉｇｈ-ｐｒｅｓｓｕｒｅ ｐｒｏｍｏｔｅｄ ｃｙｃｌｏａｄ' Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ ４１（４）, 2000, ５１５-５１９
JPN6012028780; ＨＥＮＤＲＩＣＫＳＯＮ，Ｊ．Ｂ． ｅｔ ａｌ．: 'Ａｐｐｒｏａｃｈｅｓ ｔｏ ｔｈｅ ｔｏｔａｌ ｓｙｎｔｈｅｓｉｓ ｏｆ ｌｙｃｏｒｉｎｅ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ３４（９）, 1969, ２６６７-７６
JPN6012028776; ＷＨＥＬＴＯＮ，Ｂ．Ｄ． ａｎｄ ＨＵＩＴＲＩＣ，Ａ．Ｃ．: 'Ｓｔｅｒｅｏｃｈｅｍｉｓｔｒｙ ｏｆ ａｍｉｄｏ ｄｅｒｉｖａｔｉｖｅｓ ｏｆ ３ａ，４，５，６-ｔｅｔｒａｈｙｄｒｏｉｎｄａｎ ａｎｄ ｒｅｌａｔｅｄ ｃｏｍｐｏｕｎｄｓ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ３７（１５）, 1972, ２３９６-９
JPN5008013710; ＤＡＳ，Ｐ．Ｃ． ｅｔ ａｌ．: 'Ｓｔｕｄｉｅｓ ｏｎ ｃｙｃｌｏａｌｋｙｌａｍｉｎｅ ｄｅｒｉｖａｔｉｖｅｓ' ＩＮＤＩＡＮ ＪＯＵＲＮＡＬ ＯＦ ＣＨＥＭＩＳＴＲＹ Ｖ１２ Ｎ１１, 197411, Ｐ１１３９-１１４０
JPN6012028778; ＧＩＢＳＯＮ，Ｍ．Ｓ．: '１０-Ｍｅｔｈｙｌｐｈｅｎａｎｔｈｒｉｄｉｎｅ' Ｊｏｕｒｎａｌ ｏｆ ｔｈｅ Ｃｈｅｍｉｃａｌ Ｓｏｃｉｅｔｙ , 1961, ２２４９-２２５１
JPN6012028782; ＡＲＵＭＵＧＡＭ，Ｎ． ａｎｄ ＳＨＥＮＢＡＧＡＭＵＲＴＨＩ，Ｐ．: 'Ｒｅａｃｔｉｏｎ ｏｆ １-Ａｒｙｌ-１-ｃｈｌｏｒｏ-２-ｎｉｔｒｏｓｏｃｙｃｌｏｈｅｘａｎｅｓ ｗｉｔｈ ＬＡＨ' Ｉｎｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ １３（８）, 1975, ８５７-８５８
JPN5008013714; ＰＯＮＯＭＡＲＥＶ，Ａ．Ａ．: ＭＥＴＯＤＹ ＰＯＬＵＣＨＥＮＩＹＡ ＫＨＩＭＩＣＨＥＳＫＩＫＨ ＲＥＡＫＴＩＶＯＶ Ｉ ＰＲＥＰＡＲＡＴＯＶ Ｎ１７, 1967, Ｐ１６５-１６６
Attorney, Agent or Firm:
Yoshio Kawaguchi
Makoto Ono
Chihiro Watanabe
Kenkyo Kanayama
Katsuma Osaki
Mitsuaki Tsubokura
Makoto Ono
Chihiro Watanabe
Kenkyo Kanayama
Katsuma Osaki
Mitsuaki Tsubokura