Isotechnika Inc.

Contravir Pharmaceuticals, Inc.

Ciclofilin Pharmaceuticals Corp.

Mark D Abel

Robert T Foster

Randall W Yatscoff

Daren R Ure

Bruce W Fenske

Dan J Trepanier

Shin Sugiyama

Alexander Hegmans

Selvaraj A Naicker

Jean-Michel Adam

Bruno Lohri

Roman Szweda

Hans-Jürgen Mair

Daniel Trepanier

Seetharaman Jayaraman

Analogs of cyclosporin-A are disclosed comprising modifications of the substituents as the positions of amino acids 1 and 3, according to the following Formula. The disclosed compounds include compounds having affinity for cyclophilin, including cyclophilin-A, and reduced immunosuppressivity in comparison with cyclosporin-A and analogs thereof modified solely at position 1. 

Cyclosporine analogue molecules modified at amino acid 1 and 3

This invention provides modified rapamycins that have specific monosaccharide(s), oligosaccharide(s), pseudosugar(s) or derivatives thereof attached through a linker to create rapamycin carbohydrate derivatives having enhanced pharmacokinetic and/or pharmacodynamic profiles. For example, administration of the rapamycin carbohydrate derivative results in altered pharmacokinetic profiles and reduced toxicities. Thus, the present invention provides compounds with characteristics that are distinct from other drugs in its class such as rapamycin.

Rapamycin carbohydrate derivatives

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 ISA247, and derivatives thereof. ISA247 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.

Synthesis of cyclosporin analogs

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Edmonton, Canada

Mark D Abel