公开(公告)号：US06562963B2

公开(公告)日：2003-05-13

申请号：US09919564

申请日：2001-07-31

申请人： Roberta L. Dorow ,  Silvio Campagna ,  Pasquale N. Confalone ,  Fuqiang Jin ,  Zhe Wang

发明人： Roberta L. Dorow ,  Silvio Campagna ,  Pasquale N. Confalone ,  Fuqiang Jin ,  Zhe Wang

IPC分类号： C07C23101

CPC分类号： C07C69/007 ,  C07C43/315 ,  C07C59/58 ,  C07C235/28 ,  C07D267/00 ,  C07D273/02

摘要： The present invention is directed to a process for the preparation of a compound of formula (X-a) or a pharmaceutically acceptable salt form thereof, wherein: R1 is selected from the group consisting of: C1-5 alkyl substituted with 0-5 R1a, —(CH2)r—C3-10 cycloalkyl substituted with 0-5 R1a, and —(CH2)r-aryl substituted with 0-5 R1a. Compounds of Formula (X-a) are macrocyclic molecules containing anti-succinate residues which inhibit metalloproteinases such as aggrecanase, and the production of tumor necrosis factor (TNF). The anti-succinates are formed by an Ireland Claisen rearrangement of a silyl ketene acetal which proceeds with high stereoselectivity.

摘要翻译： 本发明涉及制备式（Xa）化合物或其药学上可接受的盐形式的方法，其中：R 1选自：被0-5个R 1a取代的C 1-5烷基， - （O）R-C3-10环烷基取代有0-5个R 1a和 - （CH 2）r - 被0-5个R 1a取代的芳基。式（Ⅹa）化合物是含有抗琥珀酸残基的大环分子，其抑制金属蛋白酶如 聚集蛋白聚糖酶，以及肿瘤坏死因子（TNF）的产生。 抗琥珀酸盐由爱立信选择性的甲硅烷基乙烯酮缩醛的爱尔兰克莱森重排形成。