NAICKER, SELVARAJ,YATSCOFF, RANDALL W.,FOSTER, ROBERT T.
申请号：
CA2460685
公开号：
CA2460685C
申请日:
2002.10.17
申请国别(地区):
CA
年份:
2014
代理人:
摘要：
The invention is directed to isomeric mixtures of cyclosporine analogues thatarestructurally similar to cyclosporine A. The mixtures possess enhanced efficacyovernaturally occurring and other presently known cyclosporines and cyclosporinederivatives.Embodiments of the present invention are directed toward cis and trans-isomersofcyclosporin A analogs referred to as ISA TX247, and derivatives thereof.Mixtures ofISA TX247 isomers exhibit a combination of enhanced potency and reducedtoxicity overthe naturally occurring and presently known cyclosporins. ISA TX247 isomersandalkylated, arylated, and deuterated derivatives are synthesized bystereoselective pathwayswhere the particular conditions of a reaction determine the degree ofstereoselectivity.Stereoselective pathways may utilize a Wittig reaction, or an organometallicreagentcomprising inorganic elements such as boron, silicon, titanium, and lithium.The ratio ofisomers in a mixture may range from about 65 to 90 percent by weight of the(E)-isomer toabout 35 to 10 percent by weight of the (Z)-isomer, based on the total weightof themixture.
