Therapeutic compounds for inhibiting interleukin-12 signaling and methods for using same
申请人：Cell Therapeutics, Inc.
公开号：US06774130B2
公开（公告）日：2004-08-10
Novel heterocyclic compounds having a six membered ring structure fused to a five membered ring structure are found to be useful for the treatment and prevention of symptoms or manifestations associated with disorders affected by Interleukin-12 (“IL-12”) intracellular signaling, such as, for example, Th1 cell-mediated disorders. The therapeutic compounds, pharmaceutically acceptable derivatives (e.g., resolved enantiomers, diastereomers, tautomers, salts and solvates thereof) or prodrugs thereof, have the following general formula:
Each X, Y and Z are independently selected from a member of the group consisting of C(R3), N, N(R3) and S. Each R1, R2 and R3 is substituted or unsubstituted and is independently selected from a member of the group consisting of hydrogen, halo, oxo, C(1-20)alkyl, C(1-20)hydroxyalkyl, C(1-20)thioalkyl, C(1-20)alkylamino, C(1-20)alkylaminoalkyl, C(1-20)aminoalkyl, C(1-20)aminoalkoxyalkenyl, C(1-20)aminoalkoxyalkynyl, C(1-20)diaminoalkyl, C(1-20)triaminoalkyl, C(1-20)tetraaminoalkyl, C(5-15)aminotrialkoxyamino, C(1-20)alkylamido, C(1-20)alkylamidoalkyl, C(1-20)amidoalkyl, C(1-20)acetamidoalkyl, C(1-20)alkenyl, C(1-20)alkynyl, C(3-8)alkoxyl, C(1-11)alkoxyalkyl, and C(1-20)dialkoxyalkyl.
具有六元环结构与五元环结构融合的新颖杂环化合物被发现对治疗和预防与受白细胞介素-12（“IL-12”）细胞内信号传导受影响的疾病相关的症状或表现有用，例如Th1细胞介导的疾病。这些治疗化合物、药学上可接受的衍生物（例如，已解决的对映体、二对映体、互变异构体、盐及其溶剂）或其前药具有以下一般公式：每个X、Y和Z都独立地选自由基团中的成员，该成员包括C(R3)、N、N(R3)和S。每个R1、R2和R3都被取代或未取代，并且独立地选自由基团中的成员，该成员包括氢、卤素、氧代、C(1-20)烷基、C(1-20)羟基烷基、C(1-20)硫基烷基、C(1-20)烷基氨基、C(1-20)烷基氨基烷基、C(1-20)氨基烷基、C(1-20)氨基氧烯基、C(1-20)氨基烷氧基炔基、C(1-20)二氨基烷基、C(1-20)三氨基烷基、C(1-20)四氨基烷基、C(5-15)氨基三烷氧基氨基、C(1-20)烷基酰胺、C(1-20)烷基酰胺烷基、C(1-20)酰胺烷基、C(1-20)乙酰胺烷基、C(1-20)烯基、C(1-20)炔基、C(3-8)烷氧基、C(1-11)烷氧基烷基和C(1-20)二烷氧基烷基。
