AR043118A1 - PIRIMIDINE DERIVATIVES FOR THE PREVENTION OF HIV INFECTION - Google Patents

Abstract

Uso de un compuesto para la manufactura de un medicamento para la prevención de una infección por HIV por relaciones sexuales o contacto íntimo en la pareja, en donde el compuesto es un compuesto de la fórmula (1) un N-óxido, una sal de adición farmacéuticamente aceptable, una amina cuaternaria y una forma estereoquímicamente isomérica del mismo, donde el anillo que contiene -a1=a2-a3=a4-, y -b1=b2-b3=b4-, representa fenilo, piridilo, pirimidinilo, pirazinilo, piridazinilo; n es 0 a 5, m es 1 a 4; R1 es H, arilo, formilo, alquilcarbonilo C1-6, alquilo C1-6, alquiloxicarbonilo C1-6, alquilo C1-6 sustituido, alquilcarbonilo C1-6, alquiloxicarbonilo C1-6, alquilcarboniloxi C1-6, alquiloxi C1-6alquilcarbonilo C1-6 sustituido; R2 es hidroxi, halo, alquilo C1-6 opcionalmente sustituido, cicloalquilo C3-7, alquenilo C2-6 opcionalmente sustituido, alquinilo C2-6 opcionalmente sustituido, alquiloxi C1-6, alquiloxicarbonilo C1-6, carboxilo, ciano, nitro, amino, mono- o di(alquilo C1-6 amino), polihalometilo, polihalometiloxi, polihalometiltio, -S(=O)pR6, -NH-S(=O)pR6, -C(=O)R6, -NHC(=O)H, -C(=O)NHNH2, -NHC(=O)R6, -C(=NH)R6 o un heterociclo de 5 miembros; X1 es -NR5-, -NH-NH-, -N=N-, -O-, -C(=O)-, alcanodiilo C1-4, -CHOH-, -S-, -S(=O)p-, -X2-alcanodiilo C1-4 o alcanodiilo C1-4-X2-; R3 es NHR13, NR13R14; -C(=O)-NHR13-, -C(=O)-NR13R14-, -C(=O)-R15, -CH=N-NH-C(=O)-R16, alquilo C1-6 sustituido; alquiloxi C1-6alquilo C1-6 opcionalmente sustituido; alquenilo C2-6 sustituido; alquinilo C2-6 sustituido, alquilo C1-6 sustituido con hidroxi y un segundo sustituyentes, -C(=N-O-R8)-alquilo C1-4; R7, o -X3-R7; R4 es halo, hidroxi, alquilo C1-6, cicloalquilo C3-7, alquiloxi C1-6, ciano, nitro, polihaloalquilo C1-6, polihaloalquiloxi C1-6, aminocarbonilo, alquiloxicarbonilo C1-6, alquilcarbonilo C1-6, formilo, amino, mono- o di-(alquilo C1-4)amino, y composiciones farmacéuticas que los comprenden.Use of a compound for the manufacture of a medicament for the prevention of HIV infection by sexual intercourse or intimate contact in the couple, wherein the compound is a compound of the formula (1) an N-oxide, an addition salt pharmaceutically acceptable, a quaternary amine and a stereochemically isomeric form thereof, where the ring containing -a1 = a2-a3 = a4-, and -b1 = b2-b3 = b4-, represents phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl ; n is 0 to 5, m is 1 to 4; R 1 is H, aryl, formyl, C 1-6 alkylcarbonyl, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylcarbonyloxy, C 1-6 alkyloxyC 1-6 alkylcarbonyl 6 substituted; R2 is hydroxy, halo, optionally substituted C1-6 alkyl, C3-7 cycloalkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C1-6 alkyloxy, C1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di (C1-6 amino alkyl), polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, -S (= O) pR6, -NH-S (= O) pR6, -C (= O) R6, -NHC (= O) H, -C (= O) NHNH2, -NHC (= O) R6, -C (= NH) R6 or a 5-membered heterocycle; X1 is -NR5-, -NH-NH-, -N = N-, -O-, -C (= O) -, C1-4 alkanediyl, -CHOH-, -S-, -S (= O) p -, -X2-C1-4 alkanediyl or C1-4 alkanediyl; R3 is NHR13, NR13R14; -C (= O) -NHR13-, -C (= O) -NR13R14-, -C (= O) -R15, -CH = N-NH-C (= O) -R16, substituted C1-6 alkyl; optionally substituted C1-6 alkyloxyC 1-6 alkyl; C2-6 substituted alkenyl; C2-6 alkynyl substituted, C1-6 alkyl substituted with hydroxy and a second substituents, -C (= N-O-R8) -C 1-4 alkyl; R7, or -X3-R7; R4 is halo, hydroxy, C1-6 alkyl, C3-7 cycloalkyl, C1-6 alkyloxy, cyano, nitro, C1-6 polyhaloalkyl, C1-6 polyhaloalkyloxy, aminocarbonyl, C1-6 alkyloxycarbonyl, C1-6 alkylcarbonyl, formyl, amino , mono- or di- (C1-4 alkyl) amino, and pharmaceutical compositions comprising them.