Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use
申请人:——
公开号:US20030023087A1
公开(公告)日:2003-01-30
The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3′,5′-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, glucoma, and diseases characterized by disorders of gut motility, e.g., irritable bowel syndrome (IBS).
本发明描述了新型的亚硝酸化和/或亚硝基化的磷酸二酯酶抑制剂,以及含有至少一种亚硝酸化和/或亚硝基化的磷酸二酯酶抑制剂和,可选地,一种或多种捐赠、转移或释放一氧化氮、提高内皮源性松弛因子内源水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物和/或一种或多种血管活性剂的化合物的新型组合物。本发明还提供了含有至少一种磷酸二酯酶抑制剂和一种或多种捐赠、转移或释放一氧化氮、提高内皮源性松弛因子内源水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物和/或一种或多种血管活性剂的化合物的新型组合物。本发明还提供了治疗或预防男女性性功能障碍、增强男女性反应、以及治疗或预防由环磷酸鸟苷3',5'-单磷酸(cGMP)代谢增加引起的疾病的方法,如高血压、肺动脉高压、充血性心力衰竭、肾衰竭、心肌梗塞、稳定性、不稳定性和变异性(普林兹梅塔尔)心绞痛、动脉粥样硬化、心脏水肿、肾功能不全、肾病性水肿、肝性水肿、中风、哮喘、支气管炎、慢性阻塞性肺疾病(COPD)、囊性纤维化、痴呆、免疫缺陷、早产、痛经、良性前列腺增生(BPH)、膀胱出口梗阻、失禁、血管通透性降低的疾病,例如经皮冠状动脉成形术后(post-PTCA)、周围血管疾病、过敏性鼻炎、青光眼以及以肠道动力障碍为特征的疾病,例如肠易激综合征(IBS)。