Anti-inflammatory agents

摘要

Disclosed are novel compounds that are useful in regulating the expression of interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1), and their use in the treatment and/or prevention of cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s). Also, disclosed are compositions comprising the novel compounds, as well as methods for their preparation.

主权项

1. A method for treating non-cardiovascular inflammatory disorders mediated by VCAM-1 or IL-6, comprising administering a therapeutically effective amount of at least one compound of Formula III: or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein:
Q is CR12;V is nitrogen;U is C═O;X is selected from oxygen, sulfur, SR1, nitrogen, and CR6R7;Z is selected from unsubstituted C1-C6 alkyl and C1-C6 alkyl substituted with one or more groups selected from C1-C3 alkyl, C1-C3 alkoxy, cyclopropyl, hydroxyl, amino, and halogen;n is 0, 1, 2, 3, 4, or 5;G is selected from heterocycle, cycloalkyl, and aryl;R1 is selected from hydrogen and C1-C6 alkyl;R6, R7, and R12 are independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, heterocycle, C1-C6 alkoxy, and halogen;Rc is selected from hydrogen, C1-C6 alkyl, and C3-C6 cycloalkyl;Ra1, Ra2, and Ra3 are independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 alkoxy, C3-C6 cycloalkyl, halogen, amino, amide, hydroxyl, and heterocycle, wherein Ra1 and Ra2 and/or Ra2 and Ra3 may be connected to form a cycloalkyl or a heterocycle;Rb2 and Rb6 are independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkenyl, hydroxyl, and amino; andRb3 and Rb5 are independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, hydroxyl, and amino, whereinRb2 and Rb3 and/or Rb5 and Rb6 may be connected to form a cycloalkyl or a heterocycle;provided thatif Ra1 and Ra3 are OMe, and Q=CH, then is not at least one of Ra1, Ra2, and Ra3 is not hydrogen; andif Ra2 or Ra3 is chloro, then Ra1 is not hydrogen.