Pirimidinil and 1,3,5 - triazinilbencimidazolsulfonamidas and their use in Cancer Therapy

摘要

Pyrethroids and 1,3,5-trinitrobenzoxylamide and their pharmaceutical components, alone or in combination with radiation and / or other anticancer drugs, are used as preparations or drugs for the treatment of cancer. Requirement 1 1. Compounds of formula 1a, 1b or 1C, or a dwarf compound, a dwarf mixture, or a mixture of two or more non enantiomers, or a salt, solution, hydrate or pharmaceutical halide that can be accepted independently; in these compounds, each R1 and R2 is independent, (a) hydrogen, cyanogen, halogen or nitro; (b) C1-6 tar, c2-6 alquenilo C6, tar C2-6, c3-7 cyclopropene, arilo C6-14, aralquilo c7-15, isopropene or isopropene;or (c) -C (O) R1a, -C (O) OR1b, -C (O) NR1bR1c, -C (NRa) NR1bR1c, -OR1a, -OC (O) R1a, -OC (O) OR1a, - OC (O) NR1bR1c, -OC (= NR1a) NR1bR1c, -OS (O) R1a, -OS (O) 2R1a, -OS (O) NR1bR1c, -OS (O) 2NR1bR1c, -NR1bR1c, -NR1aC (O) R1d, -NR1aC (O) OR1d, -NR1aC (O) NR1bR1c, -NR1aC (= NR1d) NR1bR1c, -NR1aS (O) R1d, -NR1aS (O) 2R1d, -NR1aS (O) NR1bR1c, -NN) 2NR1bR1c, -SR1a, -S (O) R1a, -S (O) 2R1a, -S (O) NR1bR1c or -S (O) 2NR1bR1c; wherein each R1a, R1b, R1c and R1d is, independently, (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) R1b and R1c together with the N atom to which they are attached, form heterocyclyl; every R3 and R4 is,independently, hydrogen or C1-6 alkyl, or R3 and R4 are linked together to form a bond, C1-6 alkylene, C1-6 heteroalkylene, C2-6 alkenylene or C2-6 heteroalkenylene; each R5 is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6 alkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, C1-6-heteroaryl, heterocyclyl, C1-6-heterocyclyl or -NR5mR5n alkyl, where R5m and R5n are each, independently, hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3 cycloalkyl -7, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; each R6 is, independently, hydrogen or C1-6 alkyl; A, B,D and E are independent links, C, O, N, s, NR7, C (o),CR7 or CR7R7Where each R7 and R7 'is an independent hydrogen, halogen, C1-6 tar, c2-6 alquenilo c2-6 or c2-6, where the link between a, B, D and E may be saturated or unsaturated; provided that no more than one a, B, D and E is a link; q is C1-6 tar, c2-6 alquenileno c2-6, c2-6 tar, c3-7, leno-14, 1. Heterosexual or heterosexual; each T1 is an independent link, C1-6, - o-o-n8 -;Each T2 is a separate connection, C1-6 or - N8 tar.wherein each R8 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; and with the proviso that at least one of the two atoms that are directly linked with the group -SO2- are nitrogen; X, Y and Z are each, independently, a nitrogen atom or CR9, with the proviso that at least two of X, Y and Z are nitrogen atoms; where R9 is hydrogen or C1-6 alkyl; wherein each alkyl, alkylene, heteroalkylene, alkenyl, alkenylene, heteroalkenylene, alkynyl, alkynylene, cycloalkyl, cycloalkylene, aryl, arylene, heteroaryl, heteroarylene, heterocyclyl and heterocyclylene at R1, R2, R3, R4, R5, R6, R7, R7 ',R8, R9, R1a, R1b, R1c, R1d, R5m, R5n, Q, T1 and T2 is optionally substituted with one or more groups, each selected, independently, of (a) cyano, halo and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each optionally substituted with one or more, in a form of embodiment, one, two, three or four substituents Q1 and (c) -C (O) Ra, -C (O) ORa, -C (O) NRbRc, -C (NRa) NRbRc, -ORa, -OC (O ) Ra, -OC (O) ORa, -OC (O) NRbRc, -OC (= NRa) NRbRc, -OS (O) Ra, -OS (O) 2Ra, -OS (O) NRbRc, -OS (O ) 2NRbRc, -NRbRc, -NRaC (O) Rd, -NRaC (O) ORd, -NRaC (O) NRbRc, -NRaC (= NRd) NRbRc, -NRaS (O) Rd, -NRaS (O) 2Rd, - NRaS (O) NRbRc,-NRaS (O) 2NRbRc, -SRa, -S (O) Ra, -S (O) 2Ra, -S (O) NRbRc and -S (O) 2NRbRc, where each Ra, Rb, Rc and Rd is, independently, (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted with one or more, in a form of embodiment, one, two, three or four substituents Q1 or (iii) Rb and Rc together with the N atom to which they are attached, form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three or four substituents Q1; wherein each Q1 is independently selected from the group consisting of (a) cyano, halo and nitro;(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C (O) Re, -C (O) ORe, -C (O) NRfRg, -C (NRe) NRfRg, -ORe, -OC (O) Re, -OC (O) ORe, - OC (O) NRfRg, -OC (= NRe) NRfRg, -OS (O) Re, -OS (O) 2Re, -OS (O) NRfRg, -OS (O) 2NRfRg, -NRfRg, -NReC (O) Rh, -NReC (O) ORh, -NReC (O) NRfRg, -NReC (= NRh) NRfRg, -NReS (O) Rh, -NReS (O) 2Rh, -NReS (O) NRfRg, -NReS (O) 2NRfRg, -SRe, -S (O) Re, -S (O) 2Re, -S (O) NRfRg and -S (O) 2NRfRg, where each Re, Rf, Rg and Rh is, independently, ( i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl,O (III) RF and RG combine with N atoms to form isomerization.