Heterocyclic compounds useful for the control of Advanced Glycation End Products (AGEs)

摘要

The preparation process of these compounds, the pharmaceutical ingredients containing these compounds, and their use in the treatment of diseases caused by the formation and accumulation of the elderly (Advanced glycerine products). Current compounds are effective tools for the treatment of complications related to aging and diabetes caused by the formation and accumulation of the elderly, such as neurological disorders, nephropathy, microvascular diseases, retinopathy, hypertension, heart failure, allergies,Alzheimer's disease and dermatological disorders. Claim 1: N '- (methylsulfonyl) -1- [2-oxo-2- (thiophene-2-yl) ethyl] -1,4-dihydropyridine-3-carbohydrazide and pharmaceutically acceptable salt thereof. Claim 2: A compound of the formula (1) and pharmaceutically acceptable salt thereof; where, the dotted line on the ring containing nitrogen represents: (a) two double junctions between either (i) in C2-3 and C5-6, or (ii) in C2-3 and C4-5, or ( iii) in C3-4 and C5-6, or (b) a double between either (i) in C2-3 or (ii) in C3-4 or (iii) in C4-5 or (iv) or in C5 -6, or (c) absence of double bonding ie a saturated ring system;R1 es-cor3 or 5 member aperiodic rings: (2);G1 and G2 are independent n, NH, nr12, s or form a heterocyclic ring system, which may be partially or completely saturated; G3 is - (C1-12) tar-p or - (C1-12) tar, where p is sulfur, oxygen or nitrogen, and N is 0 or 1; Z is 1) - ch2-c (o) - RX or II; Rx is R7, - n (R7) (R10),-N 3DC (R7) (R10)-N (R7) N (R7) (R10)-N (R7) N 3DC (R7) (R10)-CH (R7) C (o) R8 or a compound containing any of the following preparations: (3);Ry is selected from the group consisting of hydrogen, linear or branched (C1-12) alkyl, (C2-12) alkenyl, (C3-7) cycloalkyl, (C5-7) cycloalkenyl, bicycloalkyl, CH2 (CO) R13, CH2 (CO) NHR14, CH2 (CO) NR14R15 and CH2 (CO) OR13; R2 every time it appears is Halogen, OR7, NO2, alkyl, aryl, heterocyclyl, formyl, oxo, -NR7R10, -N = C (R7) (R10),Sr7-so2nh2-so2-asphalt-so2-arilo, n = C (R14) (R15)-Nr14r15, - or14, perhalogiel, - O (CO) R14, - NH (CO) R14, (c2-12) alquenilo, (c3-7) cycloquilo, (C5-7) cycloquilo, bicycloquilo, bicycloquilo, bicycloquinilo, hecycloquilo, O aralquilo; MES 0, 1, 2 or 3; R3 es-r4-r5, - n (R7) n (R9), or one of the following compounds:R4 is - n (R7) r6o -,-N (R7) R6N (R7) -OR6O or -OR6N (R7) -,R6 is aspha R5 is hydrogen, asphalt, arilo, isopropene, - cor7, so2r7, - C (s) nhr7, - C (= NH) nhr7, - cor10, - C (o) nhr7 or (5);wherein R7 is H, alkyl, aryl or heterocyclyl; R8 is R7, OR7 or NR7R10; R9 is selected from the group consisting of hydrogen, alkyl, aryl, heterocyclyl, C (O) R10, -SO2R10, -C (S) NHR10, -C (N = H) NH (R10) and -C (O) NHR10 ; R10 is selected from the group consisting of H, alkyl, alkoxy, aryl and heterocyclyl; R11 is selected from the group consisting of hydrogen, linear or branched (C1-12) alkyl, (C2-12) alkenyl, (C3-7) cycloalkyl, (C5-7) cycloalkenyl, bicycloalkyl, bicycloalkenyl, heterocycloalkyl, aryl, aralkyl , heterocyclyl and Compound (6),wherein in R11 one or more heteroatoms when present are independently O, N, or S and is optionally substituted, wherein the substituents are selected from a first group consisting of halogen, hydroxy, nitro, cyano, amino, oxo and oxime or of a second group consisting of, linear or branched, (C1-8) alkyl, (C3-7) cycloalkyl, alkylcycloalkyl, perhaloalkyl, perhalocycloalkyl, aryl, aralkyl, alkylaryl, aralkoxyalkyl, perhaloaryl, alkylheterocycloalkyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, alkylcycloalkyl, heterocyclyl, alkylcycloalkyl, heterocyclyl, alkyl, cycloalkyl , perhaloheteroaryl, alkoxyalkyl, thioalkyl and thioaryl,In the case that the substance substituting for the second kind of substance is replaced by halogenated, hydrogen Xi, nitro, cyanogen, aminobenzene, oxo, hyperhalogenated tar (C1-6) and oxygen substitute, the substitute is - Co -- (CO) or -,- (CO) NH-- en...- No. fourteenth- that is...- yes.- (so)..- (SO2)- (SO2) NH-o -NH (CO) -R12 and R13 are selected independently from the following categories: a group of asphalt, asphalt, tar, perhalogiel, perhalocycloquilo, arilo, aralquilo, lease, aralcoxquilo, perhalarilo, asphalt, isocyclohexane, isocyclohexane, isocyclohexane, isocyclohexane, isocyclohexane and isocyclohexane, which are composed of one-way or separated daughter (c1-8) asphalt (c3-7), In these substances, the members of these substances can choose to use R16 instead; R14 and R15 can be independent of any group composed of the following substances: a linear or separated daughter (C1-12) asphalt, dioxane, alcoxicoquilo, alcocicycle, alcoid, alcoxiarilo, Over halogen(C2-12) alquenilo (C3-7) cicloalquilo perhalocicloalquilo haloheterocicloalquilo cianoheterocicloalquilo perhaloheterocicloalquilo (C5-7) cicloalquenilo bicicloalquilo bicicloalquenilo heterocicloalquilo arilo aralquilo heterociclilo perhaloarilo y perhaloheterociclil en donde los substituyentes de dicho grupo est n opcionalmente substituidos por R16 R16 es Halogeno hidroxi nitro ciano That is, if (I) R1 is - C (o) R3, then Z is - ch2-c (o) - RX; and (II) Z is - ch2-c (o) - Rx is O, then R7 is not hydrogen.