公开(公告)号：US5298526A

公开(公告)日：1994-03-29

申请号：US847295

申请日：1992-03-06

申请人： Donald T. Witiak ,  Ashok K. Tehim

发明人： Donald T. Witiak ,  Ashok K. Tehim

IPC分类号： C07D307/62 ,  A61K31/365

CPC分类号： C07D307/62

摘要： The present invention relates to a method for synthesis of optically pure stereogenically labile 4-substituted-2-hydroxytetronic acids from an asymmetric .alpha.-hydroxy ester. The chiron approach of the present invention utilizes a non-nucleophilic lithium amide base under kinetically controlled Claisen conditions to produce a 4-substituted-2-pheylmethoxy precursor to the 4-substituted-2-hydroxy tetronic acid. The invention further relates to the use of such optically pure compounds as potent inhibitors of platelet aggregation by working at the level of cyclooxygenase. The invention further relates to the pharmaceutical use of such compounds in the treatment of coronary artery diseases, especially in the treatment and/or prevention of atherosclerosis.

摘要翻译： 本发明涉及从不对称（α） - 羟基酯合成光学纯的立体不稳定的4-取代-2-羟基十六烷酸的方法。 本发明的凯龙疗法在动力学控制的Claisen条件下使用非亲核性的氨基化锂碱来制备4-取代-2-羟基四氢酸的4-取代的2-庚基甲氧基前体。 本发明还涉及这种光学纯化合物作为血小板聚集的有效抑制剂在环氧合酶水平上的应用。 本发明进一步涉及这些化合物在治疗冠状动脉疾病中的药物用途，特别是治疗和/或预防动脉粥样硬化。

公开(公告)号：US5095126A

公开(公告)日：1992-03-10

申请号：US464511

申请日：1990-01-12

申请人： Donald T. Witiak ,  Ashok K. Tehim

发明人： Donald T. Witiak ,  Ashok K. Tehim

IPC分类号： C07D307/62

CPC分类号： C07D307/62

摘要： The present invention relates to a method for synthesis of optically pure stereogenically labile 4-substituted-2-hydroxytetronic acids from an asymmetric .alpha.-hydroxy ester. The chiron approach of the present invention utilizes a non-nucleophilic lithium amide base under kinetically controlled Clasien conditions to produce a 4-substituted-2-pheylmethoxy precursor to the 4-substituted-2-hydroxy tetronic acid. The invention further relates to the use of such optically pure compounds as potent inhibitors of platelet aggregation by working at the level of cyclooxygenase. The invention further relates to the pharmaceutical use of such compounds in the treatment of coronary artery diseases, especially in the treatment and/or prevention of atherosclerosis.

摘要翻译： 本发明涉及从不对称α-羟基酯合成光学纯的立体不稳定的4-取代的2-羟基十六烷酸的方法。 本发明的凯龙疗法在动力学控制的Clasien条件下利用非亲核性的氨基化锂碱来制备4-取代-2-羟基四氢酸的4-取代的2-庚基甲氧基前体。 本发明还涉及这种光学纯化合物作为血小板聚集的有效抑制剂在环氧合酶水平上的应用。 本发明进一步涉及这些化合物在治疗冠状动脉疾病中的药物用途，特别是治疗和/或预防动脉粥样硬化。