HYPOPHOSPHOROUS ACID DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS

• Main Authors: BERTRAND, HUGUES-OLIVIER, TRIBALLEAU, NICOLAS, SELVAM, CHELLIAH, ACHER, FRANCINE, PIN, JEAN-PHILIPPE
• Format: Patent
• Language: English; French
• Published: 10.05.2007
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Hypophosphorous 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, or an a, beta, or a beta, g-cyclic amino acid; .R1 is H or R, R being an hydroxy or a carboxy protecting group; .Z is H or an amino protecting group R', benzyl oxycarbonyl, benzyl or benzyl substituted; .E is H or a C1-C3 alkyl, aryl, an hydrophobic group; .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, Formula (II), 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)n1COOR, 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; -R3 to R19 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 (III), NO2, SO2NH2, SO2NHR; SR, S(O)R, SO2R, benzyl; -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, with the proviso that Formula (I) does not represent the racemic (3R,S) and the enantiomeric form (3R) of 3 amino,3-carboxy-propyl-2'-carboxy-ethylphosphinic acid; 3 amino,3-carboxy-propyl-4'carboxy,2'carboxy-butanoylphosphinic acid; 3 amino,3-carboxy-propyl-2'carboxy-butanoylphosphinic acid; 3 amino,3-carboxy-propyl-3'amino, 3'carboxy-propylylphosphinic acid; and 3 amino,3-carboxypropyl-7'amino-2', 7'-dicarboxyheptylphosphinic acid, said hypophosphorous acid derivatives being diasteroisomers or enantiomers. Application as drugs.