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1. A method of treating diabetes mellitus or a microvascular or macrovascular complication of diabetes mellitus in a patient in need thereof, the method comprising administering to the patient a compound of formula 1wherein:
R1 is H or C1-6-alkyl, R2 is H or C1-10-alkyl or C2-6-alkenyl, each optionally substituted by one or more groups selected from halogen and C1-3-fluoroalkyl or optionally substituted by one or more groups selected from OR2.1, COOR2.1, CONR2.2R2.3, SR2.1, SO—R2.1, SO2—R2.1, C6-10-aryl, het, hetaryl, a mono- or bicyclic —C3-10-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, which in turn are optionally substituted by one or more groups selected from OH, halogen, OR2.1, oxo, CF3, CHF2, CH2F, C1-6-alkyl, C1-6-alkanol, C6-10-aryl, COOR2.1, CH2—NR2.2R2.3, and NR2.2R2.3, R2 is a mono- or polycyclic C3-10 cycloalkyl optionally bridged one or more times via C1-3-alkyl groups and optionally substituted by a group selected from branched or unbranched C1-6-alkanol, C1-3-fluoroalkyl, C1-3-alkylene-OR2.1, OR2.1, COOR2.1, —SO2—NR2.2R2.3, het, —NH—CO—O—(C1-6-alkyl), —NH—CO—(C1-6-alkyl), —NH—CO—O—(C6-10-aryl), —NH—CO—(C6-10-aryl), —NH—CO—O-hetaryl, —NH—CO-hetaryl, —NH—CO—O—(C1-3-alkylene)-(C6-10-aryl), —NH—CO—(C1-3-alkylene)-(C6-10-aryl), —N(C1-3-alkyl)-CO—(C1-6-alkyl), —N(C1-3-alkyl)-CO—O—(C6-10-aryl), —N(C1-3-alkyl)-CO—(C6-10-aryl), —N(C1-3-alkyl)-CO—O-hetaryl, —N(C1-3-alkyl)-CO-hetaryl, —N(C1-3-alkyl)-CO—O—(C1-3-alkylene)-(C6-10-aryl), —N(C1-3-alkyl)-CO—(C1-3-alkylene)-(C6-10-aryl), C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C3-10 cycloalkyl, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3, R2 is a mono- or polycyclic C6-10-aryl optionally substituted by OH, SH, or halogen or by one or more groups selected from OR2.1, COOR2.1, NR2.2R2.3, CH2—NR2.2R2.3, C3-10-cycloalkyl, het, C1-6-alkyl, C1-3-fluoroalkyl, CF3, CHF2, CH2F, C6-10-aryl-C1-6-alkylene, het-C1-6-alkylene, hetaryl-C1-6-alkylene, C6-10-aryl, SO2—CH3, SO2—CH2CH3 and SO2—NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, CF3, CHF2, CH2F, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3, R2 is het or hetaryl, each optionally substituted by one or more groups selected from halogen, OH, oxo, CF3, CHF2, and CH2F or by one or more groups selected from OR2.1, C1-3-alkylene-OR2.1, SR2.1, SO—R2.1, SO2—R2.1, COOR2.1, COR2.1, C1-6-alkanol, mono- or bicyclic C3-10-cycloalkyl, C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, het, hetaryl, C1-3-alkylene-OR2.1, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3, or NR1R2 together are an optionally bridged heterocyclic C4-7 ring, which contains 1, 2, or 3 heteroatoms selected from N, O, and S, and optionally substituted by one or more groups selected from OH, OR2.1, C1-3-alkylene-OR.1, oxo, halogen, C1 -6-alkyl, C6-10-aryl, COOR2.1, CH2—NR2.2—COO—R2.1, CH2—NR2.2—CO—R2.1, CH2—NR2.2—CO—CH2—NR2.2R2.3, CH2—NR2.2—SO2—C1-3-alkyl, CH2—NR2.2—SO2—NR2.2R2.3, CH2—NR2.2—CO—NR2.2R2.3, CO—NR2.2R2.3, CH2—NR2.2R2.3, and NR2.2R2.3, R3 is a C6-10-aryl optionally substituted in the ortho, para, or meta position by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, C1-6-alkyl, C1-3-fluoroalkyl, —C1-3-alkylene-OR2.1, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, O—R2.1, SO—R2.1, SO2—R2.1, COOR2.1, —CO—NH—(C1-6-alkylene)-hetaryl, —CO—NH-hetaryl, —CO—N(CH3)-het, —CO—N(CH3)—(C1-3-alkylene)-het, —CO—N(CH3)—(C1-3-alkylene)-hetaryl, —CO—N(C3-7-cycloalkyl)-het, —CO—NR2.2R2.3, —CO—NH—(C1-6-alkylene)-het, NR2.2—CO—R2.1, C6-10-aryl, C6-10-aryl-C1-2-alkylene, het-C1-2-alkylene, het, —CO-het, CO—N(CH3)—C3-7-cycloalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-2-alkylene, hetaryl-C1-2-alkylene, and hetaryl, each optionally substituted by one or more groups selected from OH, halogen, —C1-3-fluoroalkyl, oxo, methyl, and phenyl, R3 is het and hetaryl, each optionally substituted by one or more groups selected from halogen, C1-3-fluoroalkyl, CN, OH, oxo, —C1-6-alkyl, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, SO—R2.1, SO2—R2.1, —O—R2.1, —COOR2.1, SO2—(CH3), SO2—(CH2—CH3), C6-10-aryl, het, C3-7-cycloalkyl, and hetaryl, each optionally substituted by one or more groups selected from OH, halogen, —C1-3-fluoroalkyl, C1-6-alkyl, C6-10-aryl, —COO(C1-3-alkyl), and O—(C1-3-alkyl), R3 is —O—R3.1, wherein R3.1 is a group selected from —C1-6-alkyl, —C6-10-aryl, —C1-3-alkylene-C6-10-aryl, hetaryl, and het, each optionally substituted in the ortho, para, or meta position by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, C1-6-alkyl, C1-3-fluoroalkyl, CO—(C1-5-alkyl), —CO—(C1-3-fluoroalkyl), —CO—NH—(C1-6-alkylene)-hetaryl, —CO—N(C1-3-alkyl)-(C1-6-alkylene)-hetaryl, —CO—N(C1-3-alkyl)-het, —CO—N(C3-7-cycloalkyl)-het, —C1-3-alkylene-OR2.1, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, O—R2.1, SO—R2.1, SO2—R2.1, COOH, COO—(C1-4-alkyl), —O—C1-3-alkylene-N(C1-3-alkyl)2, CO—NR2.2R2.3, NR2.2—CO—R2.1, C6-10-aryl, C6-10-aryl-C1-2-alkylene, het-C1-2-alkylene, —CO-het, het, —CO—C3-7-cycloalkyl, —CO—N(C1-3-alkyl)-C3-7-cycloalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-2-alkylene, hetaryl-C1-2-alkylene, and hetaryl, each optionally substituted by 1, 2, 3, or 4 groups independently selected from F, Cl, Br, methyl, O-methyl, ethyl, O-ethyl, OH, oxo, and CF3, and R4 is H, CN, OH, CF3, CHF2, CH2F, F, methyl, ethyl, —O—(C1-3-alkyl), —C1-3-alkylene-OH, —COO(C1-3-alkyl), —CO-het, —(C1-2-alkylene)-NH—SO2—(C1-2-alkyl), —(C1-2-alkylene)-N(C1-3-alkyl)-SO2—(C1-2-alkyl), —(C1-2-alkylene)-O—(C1-2-alkylene)-C6-10-aryl, —C1-3-alkylene-O—C1-3-alkyl, —(C1-2-alkylene)-N(C1-3-alkyl)-CO—(C1-2-alkyl), —NH—CO—(C1-3-alkylene)-O—(C1-3-alkyl), —C1-3-alkylene-NH—CO—(C1-3-alkyl), —C1-3-alkylene-NH—CO—(C1-3-alkylene)-N(C1-3-alkyl)2, —O—(C1-2-alkylene)-(C6-10-aryl), —C1-3-alkylene-NH—CO—(C1-3-alkylene)-O—(C1-3-alkyl), —CO—(C6-10-aryl), or —(C1-2-alkylene)-N(C1-3-alkyl)-CO—(C1-2-alkylene)-O—(C1-3-alkyl), wherein the aryl thereof is optionally substituted by one or more groups selected from F, Cl, Br, methyl, ethyl, propyl, isopropyl, cyclopropyl, —O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —O-cyclopropyl, —OH, and CF3, or R3 and R4 together form a mono- or bicyclic, unsaturated, saturated or partially saturated heterocycle, which contains 1, 2 or 3 heteroatoms selected from N, O, and S, and is optionally substituted by one or more groups selected from halogen, OH, oxo, C1-3-fluoroalkyl, CN, C1-6-alkyl, —O—R2.1—COOR2.1, SO—R2.1, SO2—R2.1, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, C6-10-aryl, C3-7-cycloalkyl, het, and hetaryl, wherein: R2.1 is H or is a group selected from C1-6-alkyl, C1-6-alkanol, C1-3-haloalkyl, mono- or bicyclic, —C3-10-cycloalkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, het-C1-6-alkylene, C3-10-cycloalkyl-C1-6-alkylene, a mono- or bicyclic C6-10-aryl, heteroaryl, and het, each optionally substituted by one or more groups selected from OH, O—(C1-3-alkyl), halogen, C1-6-alkyl, and C6-10-aryl, R2.2 and R2.3 are independently H or a group selected from C1-6-alkyl, mono- or bicyclic C3-10 cycloalkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C6-10-aryl, het, hetaryl, CO—NH2, CO—NHCH3, —CO—N(CH3)2, SO2—(C1-C2-alkyl), CO—R2.1 and COOR2.1, each optionally substituted by one or more groups selected from among OH, halogen, C1-6-alkyl, C6-10-aryl, and COOR2.1, het is a three- to eleven-membered, mono- or bicyclic, saturated or partially saturated, optionally anellated or optionally bridged heterocycle which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, hetaryl is a five- to ten-membered, mono- or bicyclic, optionally anellated heteroaryl, which contains 1, 2, 3, or 4 heteroatoms selected independently from N, S, or O, and cycloalkyl is saturated or partially saturated, or a pharmacologically acceptable salt thereof. |
