Title:
チオホスフィン(チオホスホン)酸誘導体およびそれらの治療適用
Document Type and Number:
Japanese Patent JP2010535193
Kind Code:
A
Abstract:
The invention relates to thiophosphi(o)nic acid derivatives having formula (I) wherein. M is a [C(R3,R4)]n1-C(E,COOR1,N(H,Z)) group, or an optionally substituted Ar—CH(COOR1,N(H,Z)) group (Ar designating an aryl or an heteroaryl group), or an α, β cyclic aminoacid group such as, formula (II) or a β, γ-cyclic aminoacid group such as, formula (III). R1 is H or R, R being an hydroxy or a carboxy protecting group, such as C1-C3 alkyl, Ar (being aryl or heteroaryl), Z is H or an amino protecting group R′, such as C1-C3 alkyl, C1-C3 acyl, Boc, Fmoc, COOR, benzyl oxycarbonyl, benzyl or benzyl substituted such as defined with respect to Ar; E is H or a C1-C3 alkyl, aryl, an hydrophobic group such as (CH2)n1-alkyl, (CH2)n1-aryl (or heteroaryl), such as a benzyl group, or a xanthyl, alkyl xanthyl or alkyl thioxanthyl group, or —(CH2)n1-cycloalkyl, —(CH2)n—(CH2—Ar)2, a chromanyl group, particularly 4-methyl chromanyle, indanyle, tetrahydro naphtyl, particularly methyl-tetrahydronaphtyl; or M is OM′, wherein M′ is as above defined for M; R2 is selected in the group comprising: D-CH(R6)—C—(R7,R8)—(R11,R12)CH—C(R9.R10)-D-CH(OH)-D-[C(R13,R14)]n3—C[(R15,R16,R17]n4-D-CH2—(R18)CH═C(R19)-D-(M1)n6-CO-D-C(R,R′)—O-D-O—, formula (IV), PO(OH)2—CH2 or (PO(OH)2—CH2), (COOH—CH2)—CH2— with -D=H, OH, OR, (CH2)n2OH, (CH2)n1OR, COOH, COOR, (CH2)n2COOH, (CH2)n1C00R, SR, S(OR), SO2R, NO2, heteroaryl, C1-C3 alkyl, cycloalkyl, heterocycloalkyl, (CH2)n2-alkyl, (COOH, NH2)—(CH2)u1-cyclopropyl-(CH2)u2—, CO—NH-alkyl, Ar, (CH2)n2—Ar, CO—NH—Ar, R being as above defined and Ar being an optionally substituted aryl or heteroaryl group, —R3 to R19, identical or different, being H, OH, OR, (CH2)n2OH, (CH2)n1OR, COOH, COOR, (CH2)n2COOH, (CH2)n1COOR, C1-C3 alkyl, cycloalkyl, (CH2)n1-alkyl, aryl, (CH2)n1-aryl, halogen, CF3, SO3H, (CH2)XPO3H2, with x=0, 1 or 2, B(OH)2, formula (V), NO2, SO2NH2, SO2NHR; SR, S(O)R, SO2R, benzyl; one of R11 or R12 being COOR, COOH, (CH2)n2—COOH, (CH2)n2—COOR, PO3H2 the other one being such as defined for R9 and R10;—one Of R15, R16 and R17 is COON or COOR, the others, identical or different, being such as above defined;—one of R18 and R19 is COOH or COOR, the other being such as above defined;—M1 is an alkylene or arylene group;—n1=1, 2 or 3;—n2=1, 2 or 3,—n3=0, 1, 2 or 3 and—n4=1, 2 or 3;—n5=1, 2 or 3;—n6=0 or 1,—u1 and u2, identical or different=0, 1 or 2, Ar, and alkyl groups being optionally substituted by one or several substituents on a same position or on different positions, said substituents being selected in the group comprising: OH, OR, (CH2)n1OH, (CH2)n1OR, COOH, COOR, (CH2)n1C00H, (CH2)n1COOR, C1-C3 alkyl, cycloalkyl, (CH2)n1-alkyl, aryl, (CH2)n1-aryl, halogen, CF3, SO3H, (CH2)xPO3H2, with x=0, 1 or 2, B(OH)2, formula (V), NO2, SO2NH2, SO2NHR; SR, S(O)R, SO2R, benzyl; R being such as above defined.
Inventors:
Asher Francine
Selvam cheria
Pin Jean-Philippe
Selvam cheria
Pin Jean-Philippe
Application Number:
JP2010518779A
Publication Date:
November 18, 2010
Filing Date:
August 01, 2008
Export Citation:
Assignee:
Saintur Nacional De La Rousche Châtantique Séenneres
International Classes:
C07F9/38; A61K9/20; A61K9/48; A61K31/662; A61P25/00; A61P25/04; A61P25/08; A61P25/22; A61P25/28; A61P25/30; A61P43/00; C07F9/40
Domestic Patent References:
| JP2003532656A | 2003-11-05 | |||
| JP2005507857A | 2005-03-24 |
Foreign References:
| WO2007052169A2 | 2007-05-10 | |||
| WO1999047101A2 | 1999-09-23 |
Other References:
JPN6013029989; ＶＡＲＬＥＴ，Ｊ．Ｍ． ｅｔ ａｌ．: 'Ｓｙｎｔｈｅｓｉｓ ａｎｄ ｒｅｄｕｃｔｉｖｅ ａｍｉｎａｔｉｏｎ ｏｆ ｐｈｏｓｐｈｏｎｏｐｙｒｕｖａｔｅｓ： ｐｒｅｐａｒａｔｉｏｎ ｏｆ ２-ａｍｉｎｏ-２-ｃａｒｂｏｘｙａｌｋｙｌｐｈｏｓｐ' Ｃａｎａｄｉａｎ Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｓｔｒｙ ５７（２４）, 1979, ３２１６-２０
JPN6013029991; ＬＯＦＦＲＥＤＯ，Ｗ．Ｍ． ａｎｄ ＴＳＡＩ，Ｍ．Ｄ．: 'Ｐｈｏｓｐｈｏｌｉｐｉｄｓ ｃｈｉｒａｌ ａｔ ｐｈｏｓｐｈｏｒｕｓ： ｓｙｎｔｈｅｓｉｓ ａｎｄ ｃｏｎｆｉｇｕｒａｔｉｏｎａｌ ａｓｓｉｇｎｍｅｎｔ ｏｆ ｐｈｏｓｐｈｏｒｏｔｈｉｏａｔｅ ａｎ' Ｂｉｏｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ １８（１）, 1990, ７８-８４
JPN6013029993; ＢＡＲＡＮＩＡＫ，Ｊ． ｅｔ ａｌ．: 'Ｏｘａｔｈｉａｐｈｏｓｐｈｏｌａｎｅ Ａｐｐｒｏａｃｈ ｔｏ Ｎ- ａｎｄ Ｏ-Ｐｈｏｓｐｈｏｒｏｔｈｉｏｙｌａｔｉｏｎ ｏｆ Ａｍｉｎｏ Ａｃｉｄｓ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ６７（２１）, 2002, ７２６７-７２７４
JPN6013029994; Ｄｅ ＢＯＮＴ，Ｄ．Ｂ．Ａ． ｅｔ ａｌ．: 'Ｓｏｌｉｄ-ｐｈａｓｅ ｓｙｎｔｈｅｓｉｓ ｏｆ Ｏ-ｐｈｏｓｐｈｏｒｏｔｈｉｏｙｌｓｅｒｉｎｅ- ａｎｄ -ｔｈｒｅｏｎｉｎｅ-ｃｏｎｔａｉｎｉｎｇ ｐｅｐｔｉｄｅｓ ａｓ ｗｅｌｌ ａｓ ｏｆ Ｏ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ５８（６）, 1993, １３０９-１７
JPN6013029991; ＬＯＦＦＲＥＤＯ，Ｗ．Ｍ． ａｎｄ ＴＳＡＩ，Ｍ．Ｄ．: 'Ｐｈｏｓｐｈｏｌｉｐｉｄｓ ｃｈｉｒａｌ ａｔ ｐｈｏｓｐｈｏｒｕｓ： ｓｙｎｔｈｅｓｉｓ ａｎｄ ｃｏｎｆｉｇｕｒａｔｉｏｎａｌ ａｓｓｉｇｎｍｅｎｔ ｏｆ ｐｈｏｓｐｈｏｒｏｔｈｉｏａｔｅ ａｎ' Ｂｉｏｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ １８（１）, 1990, ７８-８４
JPN6013029993; ＢＡＲＡＮＩＡＫ，Ｊ． ｅｔ ａｌ．: 'Ｏｘａｔｈｉａｐｈｏｓｐｈｏｌａｎｅ Ａｐｐｒｏａｃｈ ｔｏ Ｎ- ａｎｄ Ｏ-Ｐｈｏｓｐｈｏｒｏｔｈｉｏｙｌａｔｉｏｎ ｏｆ Ａｍｉｎｏ Ａｃｉｄｓ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ６７（２１）, 2002, ７２６７-７２７４
JPN6013029994; Ｄｅ ＢＯＮＴ，Ｄ．Ｂ．Ａ． ｅｔ ａｌ．: 'Ｓｏｌｉｄ-ｐｈａｓｅ ｓｙｎｔｈｅｓｉｓ ｏｆ Ｏ-ｐｈｏｓｐｈｏｒｏｔｈｉｏｙｌｓｅｒｉｎｅ- ａｎｄ -ｔｈｒｅｏｎｉｎｅ-ｃｏｎｔａｉｎｉｎｇ ｐｅｐｔｉｄｅｓ ａｓ ｗｅｌｌ ａｓ ｏｆ Ｏ' Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ ５８（６）, 1993, １３０９-１７
Attorney, Agent or Firm:
Norihiko Hibi
Einosuke Kishimoto
Akira Watanabe
Matsumura Naoto
Einosuke Kishimoto
Akira Watanabe
Matsumura Naoto