Thiophosphi(o)nic acid derivatives and their therapeutical applications

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, &ggr;-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.

Dependencies are inferred from the claim text.