| 摘要 |
Peptidomiméticos de horquilla beta fijados a patrón de la fórmula general (1), en la cual Z es una cadena fijada a patrón de 12 residuos de alfa-aminoácidos que, dependiendo de sus posiciones de cadena (contando a partir del aminoácido N-terminal) son Gly ó Pro, o de ciertos tipos y sales de los mismos, que tienen la propiedad de inhibir selectivamente el crecimiento de, o exterminar, microorganismos tales como Pseudomonas aeruginosa y Acinetobacter. Los mismos pueden ser usados como desinfectantes para alimentos, cosméticos, medicamentos u otros materiales que contengan nutrientes, o como medicamentos para tratar o prevenir infecciones. Estos peptidomiméticos de horquilla beta pueden ser fabricados por procesos que se basan en una estrategia de síntesis en fase mixta de sólido y solución. Reivindicación 1: Compuestos de la fórmula general (1) en la cual la porción de fórmula (2) es un grupo de una de las fórmulas del grupo de fórmulas (3), en las cuales -C(=O)-B- es el residuo de un L-alfa-aminoácido con B que es un residuo de la fórmula -NR20CH(R71)- o el enantiómero de uno de los grupos A1 a A69 como se definen en la presente más adelante; -A-> es un grupo de una de las fórmulas del grupo de fórmulas (4); R1 es H; alquilo inferior; ó aril-alquilo inferior ; R2 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sSR56; -(CH2)m(CHR61)sNR33R34; -(CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R1 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sSR56; -(CH2)m(CHR61)sNR33R34; -(CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R4 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sSR56; -(CH2)m(CHR61)sNR33R34; - (CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)p(CHR61)sCOOR57; -(CH2)p(CHR61)sCONR58R59; -(CH2)p(CHR61)sPO(OR60)2; -(CH2)p(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R5 es alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R6 es H; alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)S SO2R62; ó -(CH2)o(CHR61)sC6H4R8; R7 es alquilo; alquenilo; -(CH2)q(CHR61)sOR55; -(CH2)q(CHR61)sNR33R34; -(CH2)q(CHR61)sOCONR33R75; -(CH2)q(CHR61)sNR20CONR33R82; -(CH2)r(CHR61)sCOOR57; -(CH2)r(CHR61)sCONR58R59; -(CH2)r(CHR61)sPO(OR60)2; -(CH2)r(CHR61)SO2R62; ó -(CH2)r(CHR61)sC6H4R8; R8 es H; Cl; F; CF3; NO2; alquilo inferior; alquenilo inferior; arilo; aril-alquilo inferior; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)NR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59 ; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sCOR64; R9 es alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R10 es alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R11 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sNR33R34; -(CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R12 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sSR56; -(CH2)m(CHR61)sNR33R34; -(CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)r(CHR61)sCOOR57; -(CH2)r(CHR61)sCONR58R59; -(CH2)r(CHR61)sPO(OR60)2; -(CH2)r(CHR61)sSO2R62; ó -(CH2)r(CHR61)sC6H4R8; R13 es alquilo; alquenilo; -(CH2)q(CHR61)sOR55; -(CH2)q(CHR61)sSR56; -(CH2)q(CHR61)sNR33R34; -(CH2)q(CHR61)sOCONR33R75; -(CH2)q(CHR61)NR20CONR58R58; -(CH2)q(CHR61)sCOOR57; -(CH2)q(CHR61)sCONR58R59; -(CH2)q(CHR61)sPO(OR60)2; -(CH2)q(CHR61)sSO2R62; ó -(CH2)q(CHR61)sC6H4R8; R14 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sNR33R34; -(CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)q(CHR61)sCOOR57; -(CH2)q(CHR61)sCONR58R59; -(CH2)q(CHR61)sPO(OR60)2; -(CH2)q(CHR61)sSOR62; ó -(CH2)q(CHR61)sC6H4R8; R15 es alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R16 es alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)CONR58R58; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R17 es alquilo; alquenilo; -(CH2)q(CHR61)sOR55; -(CH2)q(CHR61)sSR56; -(CH2)q(CHR61)sNR33R34; -(CH2)q(CHR)sOCONR33R75; -(CH2)q(CHR61)NRCONR58R59; -(CH2)q(CHR61)COOR57; -(CH2)q(CHR61)sCONR58R59; -(CH2)q(CHR61)sPO(OR60)2; -(CH2)q(CHR61)sSO2R62; ó -(CH2)q(CHR61)sC6H4R8; R18 es alquilo; alquenilo; -(CH2)p(CHR61)sOR55; -(CH2)p(CHR61)sSR56; -(CH2)p(CHR61)sNR33R34; -(CH2)p(CHR61)sOCONR33R75; -(CH2)p(CHR61)sNR20CONR33R82; -(CH2)p(CHR61)sCOOR57; -(CH2)p(CHR61)sCONR58R59; -(CH2)p(CHR61)sPO(OR60)2; -(CH2)p(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R19 es alquilo inferior; -(CH2)p(CHR61)OR55; -(CH2)p(CHR61)sSR56; -(CH2)p(CHR61)sNR33R34; -(CH2)p(CHR61)sOCONR33R75; -(CH2)p(CHR61)sNR20CONR33R82; -(CH2)p(CHR61)sCOOR57; -(CH2)p(CHR61)sCONR58R59; -(CH2)p(CHR61)sPO(OR60)2; -(CH2)p(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; ó R18 y R19 tomados conjuntamente pueden formar: -(CH2)2-6-; -(CH2)2O(CH2)2-; -(CH2)2S(CH2)2-; ó -(CH2)2NR57(CH2)2-; R20 es H; alquilo; alquenilo; ó aril-alquilo inferior; R21 es H; alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R22 es H; alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; - (CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R23 es alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R24 es alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CHZ)o(CHR61)C6H4R8; R25 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sSR56; -(CH2)m(CHR61)sNR33R34; -(CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)SO2R62; ó -(CH2)o(CHR61)sC6H4R8; R26 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sSR56; -(CH2)m(CHR61)sNR33R34; -(CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; ó R25 y R26 tomados conjuntamente pueden formar: -(CH2)2-6-; -(CH2)rO(CH2)r-; -(CH2)rS(CH2)r-; ó - (CH2)rNR57(CH2)r-; R27 es H; alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R28 es alquilo; alquenilo; -(CH2)o(CHR61)s-OR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R29 es alquilo; alquenilo; -(CH2)o(CHR61)sOR55; -(CH2)o(CHR61)sSR56; -(CH2)o(CHR61)sNR33R34; -(CH2)o(CHR61)sOCONR33R75; -(CH2)o(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR6)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R30 es H; alquilo; alquenilo; ó aril-alquilo inferior; R31 es H; alquilo; alquenilo; -(CH2)p(CHR61)OR55; -(CH2)p(CHR61)sNR33R34; -(CH2)p(CHR61)sOCONR33R75; -(CH2)p(CHR61)sNR20CONR33R82; -(CH2)o(CHR61)sCOOR57; -(CH2)o(CHR61)sCONR58R59; -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R32 es H; alquilo inferior; ó aril-alquilo inferior; R33 es H; alquilo, alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sNR34R63; -(CH2)m(CHR61)sOCONR75R82; -(CH2)m(CHR61)sNR20CONR78R82; -(CH2)o(CHR61)sCOR64; -(CH2)o(CHR61)s-CONR58R59, -(CH2)o(CHR61)sPO(OR60)2; -(CH2)o(CHR61)sSO2R62; ó -(CH2)o(CHR61)sC6H4R8; R34 es H; alquilo inferior; arilo, ó aril-alquilo inferior; R33 y R34 tomados conjuntamente pueden formar: -(CH2)2-6-; -(CH2)2O(CH2)2-; -(CH2)2S(CH2)2-; ó -(CH2)2NR57(CH2)2-; R35 es H; alquilo; alquenilo; -(CH2)m(CHR61)sOR55; -(CH2)m(CHR61)sNR33R34; -(CH2)m(CHR61)sOCONR33R75; -(CH2)m(CHR61)sNR20CONR33R82; -(CH2)p(CHR61)sCOOR57; -(CH2)p(CHR61)sCONR58R59; -(CH2)p(CHR61)sPO(OR60)2; -(CH2)p(CHR61)sSO2R62; ó -(CH2)p(CHR61)sC |
