NON-CLEAVABLE POLYMER CONJUGATED WITH ALPHA V BETA 3 INTEGRIN THYROID ANTAGONISTS
申请人:NANOPHARMACEUTICALS, LLC
公开号:US20170348425A1
公开(公告)日:2017-12-07
Chemical compositions and methods of synthesis thereof. The compositions disclosed and described herein are directed toward and classified as anti-angiogenic thyrointegrin antagonists, which may be capable of reacting with one or more cell surface receptors of the integrin αvβ3 receptor family. Anti-angiogenic thyrointegrin antagonists or derivatives thereof are conjugated via a non-cleavable linker having an amine, diamine or triazole linkage to polymers of Polyethylene Glycol, cyclodextrin, chitosan, alginic acid or hyaluronic acid, forming a single chemical entity. Utility of the compositions disclosed may treat angiogenesis-mediated disorders such as Cancer (Solid tumors and Liquid tumors), ocular disorders (Diabetic Retinopathy and Age-related Macular Degeneration), inflammatory disorders (arthritis, osteoarthritis), atherosclerosis, lesions, and dermatology (Rosacea, Psoriasis, skin cancer) and diseases mediated or dependent upon the generation of new blood cells via angiogenesis to persist and the treatment thereof or dependent on antagonizing the formation of new blood vessels to slow or eliminate angiogenic pathways.
化学成分及其合成方法。本文所披露和描述的化合物是针对和分类为抗血管生成的甲状腺整合素拮抗剂,可能能够与整合素αvβ3受体家族的一个或多个细胞表面受体发生反应。抗血管生成的甲状腺整合素拮抗剂或其衍生物通过非可切割的连接剂(具有胺、二胺或三唑键)与聚合物聚乙二醇、环糊精、壳聚糖、海藻酸或透明质酸结合,形成单一的化学实体。所披露的化合物可用于治疗血管生成介导的疾病,如癌症(实体肿瘤和液体肿瘤)、眼部疾病(糖尿病视网膜病变和年龄相关性黄斑变性)、炎症性疾病(关节炎、骨关节炎)、动脉粥样硬化、损伤和皮肤科疾病(酒渣鼻、银屑病、皮肤癌)以及通过血管生成产生新血细胞以维持和治疗相关的疾病,或通过拮抗新血管形成来减缓或消除血管生成途径。