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Cyclosporine analogue mixtures and their use as immunomodulators
专利权人:
ファーマ;アイソテクニカ;アイソテクニカ ファーマ インク.;インク.
发明人:
セルヴァレイ ネイッカー,ランダル ダブリュー ヤトコフ,ロバート ティー フォスター
申请号:
JP2009140608
公开号:
JP5272140B2
申请日:
2009.06.11
申请国别(地区):
JP
年份:
2013
代理人:
摘要:
The invention is directed to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A . The mixtures possess enhanced efficacy and reduced toxicity over the individual isomers and over naturally occurring and other presently known cyclosporines and cyclosporine derivatives. Embodiments of the present invention are directed toward cis and trans -isomers of cyclosporin A analogs referred to as ISA TX 247, and derivatives thereof. Mixtures of ISA TX 247 isomers exhibit a combination of enhanced potency and reduced toxicity over the naturally occurring and presently known cyclosporins. ISA TX 247 isomers and alkylated, arylated, and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. Stereoselective pathways may utilize a Wittig reaction, or an organometallic reagent comprising inorganic elements such as boron, silicon, titanium, and lithium. The ratio of isomers in a mixture may range from about 10 to 90 percent by weight of the (E)-isomer to about 90 to 10 percent by weight of the (Z)-isomer, based on the total weight of the mixture.
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中国工程科技知识中心
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