COMPUESTOS PARA ANULAR RESISTENCIAS A MEDICAMENTOS

• Main Authors: MEZO, IMRE, TEPLAN, ISTVAN, CSUKA, ORSOLYA, SARKADI, BALAZS, MAGOCSI, MARIA, SEPRODI, JANOS
• Format: Patent
• Language: Spanish
• Published: 16.08.2000
• Edition: 7
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

LA INVENCION DESTACA NUEVOS DERIVADOS PEPTIDICOS DENOMINADOS REVERSINAS, Y POSIBILITA SU UTILIZACION EN UN METODO DE REDUCCION DE LA ACTIVIDAD DE LA PROTEINA TRANSPORTADORA DE MULTIPLES MEDICAMENTOS MDR1, CON EL OBJETO DE EVITAR LA RESISTENCIA A MULTIPLES MEDICAMENTOS EN MAMIFEROS. LOS DERIVADOS PEPTIDICOS, TIENEN LA FORMULA (I) X{SUP,1}{SUB,N}-X{SUP,2}-X{SUP,3}(X{SUP,4}){SUB,N}-X{SUP,5}, DONDE N ES 0 O 1, Y CADA N ES IGUAL O DISTINTO; X{SUP,1} ES BOC, BOC-ASU, Z-ASU, BENCILOXICARBONILO, GLU(OBCZL)-OBZL, TRP-OME, TRP-PHE-OME, PHE-TRP-OME, PHE-PHE-OTBU, TRP-TRP-OTBU, INDOLOACETILO, BENZOILO, UNA ALQUILAMINA DE 1-4 CARBONOS, DIBENCILAMIDA, TRIPTAMIDA, 1-AMINO-ADAMANTINO, AMINOMETILCICLOHEXANO, INDOLINA, FENILMETILAMIDA O DICICLOHEXILAMIDA; X{SUP,2} ES GLU(OBZL, ASP(OBZL), SUCCINILO, O,O-DIBENZOLITARTAROILO, DIFENOILO, MUCONILO, THX, CPA, ASU, NAL, PEN, PHG, DBT, LYS(BOC), LYS(Z), CYS(BZL), THR(BZL), GLU(OTBU), TRET-LEU, LEU, NLE, PRO, PHE, TYR(BZL), O SER(BAL); X{SUP,3} ES ASP, ASU, LYS, GLU,TRP, THX, CPA, NAL, PEN, PHG, DBT, GLU(OTBU), TERT-LEU, LEU, NLE, PRO, TYR, PHE O TYR(BZL); X{SUP,4} ES BOCGLU(OBZL), GLU(OBZL), ASU, OBCL, BZL, BOC, BOC-LYS(BOC), ZGLU(OTBU), ASP(OBZL), ASP(OBZL)-OBZL, BENCILOXICARBONILO, O(CICLO-HEXILO), ESTER DE FLUORENILMETILO, GLU(OTBU), GLU(OTBU)OBZL, 1-AMINO-ADAMANTINO, AMINOMETILCICLOHEXANO, INDOLINA, FENILETLAMINA, O DICICLOHEXILAMIDA; Y X{SUP,5} ES OME, OBZL, OTBU, PHE-OME, -O-(CICLOHEXILO), TRP-OME, (CLOROFENIL)ISOBUTILAMIDA, ESTER DEE FLUORENILMETILO, ONP, 1-AMINOADAMANTANO, AMINOMETILCICLOHEXANO, INDOLINA, FENILETILAMIDA, O DICICLOHEXILAMIDA. The invention features novel peptide derivatives called Reversins, and provides for their use in a method of reducing the activity of the multi-drug transporter protein MDR1 in order to overcome multidrug resistance in a mammal. The peptide derivatives are of the formula (I) X1n-X2-X3(X4)n-X5, wherein n is 0 or 1, and each n is the same or different; X1 is BOC, BOC-Asu, Z-Asu, benzyloxycarbonyl, Glu(OBzl)-OBzl, Trp-OMe, Trp-Phe-OMe, Phe-Trp-OMe, Phe-Phe-OtBu, Trp-Trp-OtBu, indoloacetyl, benzoyl, an alkylanine of 1-4 carbons, dibenzylamide, tryptamide, 1-amino-adamantine, aminomethylcyclohexane, indoline, phenylethylamide or dicyclohexylamide; X2 is Glu(OBzl), Asp(OBzl), succinyl, O,O-dibenzoyltartaroyl, diphenoyl, muconyl, Thx, Cpa, Asu, Nal, Pen, Phg, Dbt, Lys(BOC), Lys(Z), Cys(Bzl), Thr(Bzl), Glu(OtBu), tert.-Leu, Leu, Nle, Pro, Phe, Tyr(Bzl), or Ser(Bal); X3 is Asp, Asu, Lys, Glu, Trp, Thx, Cpa, Nal, Pen, Phg, Dbt, Glu(OtBu), tert.-Leu, Leu, Nle, Pro, Tyr, Phe, or Tyr(Bzl); X4 is BOC-Glu(OBzl), Glu(OBzl), Asu, OBzl, Bzl, BOC, BOC-Lys(BOC), Z-Glu(OtBu), Asp(OBzl), Asp(OBz)-OBzl, benzyloxycarbonyl, O-(cyclo-hexyl), fluorenylmethyl ester, Glu(OtBu), Glu(OtBu)-OBzl, 1-amino-adamantine, aminomethylcyclohexane, indoline, phenylethylarnide, or dicyclohexylamide; and X5 is OMe, OBzl, OtBu, Phe-OMe, -O-(cyclohexyl), Trp-OMe, (chlorophenyl)-isobutylamide, fluorenylmethyl ester, ONp, 1-aminoadamantane, aminomethylcyclohexane, indoline, phenylethylamide, or dicyclohexylamide.