Chiron Corporation

Other

Verena D Huebner

Rajinder Paul Singh

Manoj C Desai

Xiaodong Lin

Liya Chen

Beata Krywult

Liang Wang

Ian James

Thayalan Navaratnam

Rob Trainor

Jennifer C Moore

Daniel V Santi

Gavin D Dollinger

Surinder Kaur

Estrogen receptor-modulating pyrazole compounds are described in addition to methods and compositions for treating or preventing estrogen receptor-mediated disorders. The compounds described have been found to have unexpected and surprising activity in modulating estrogen receptor activity. Thus, the compounds of the present invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

Estrogen receptor modulators

Isoxazole estrogen receptor agonist and antagonist compounds having unexpected and surprising activity in modulating estrogen receptor activity are described. In addition, methods and compositions for treating or preventing estrogen receptor-mediated disorders are disclosed. The compounds, methods, and compositions of the invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

Compounds are quickly selected from a combinatorial library by contacting the library with a target (e.g., receptor), separating non-binding compounds from compound-target complexes, and analyzing the complexes or eluted compound by mass spectroscopy. SAR information is obtained by performing this selection at two or more different ratios of compound to target.

Affinity selection of ligands by mass spectroscopy

A method of preparing a mixture of peptides having a known composition and containing a peptide of a desired amino acid sequence is disclosed. The method involves three essential steps. First a given amount of a mixture of amino acyl or peptide derivatized resin is divided into a number of pools with each pool containing an equal molar amount of the resin mixture. Second a different single amino acid is coupled to the resin mixture in each of the pools and the coupling reaction is driven to completion. The peptide mixtures in each of the pools are then mixed together to obtain a complex peptide mixture containing each peptide in retrievable and analyzable amounts. The steps can be repeated to lengthen the peptide chains and methods can be employed to retrieve the desired peptide from the mixture and carry out analyses such as the determination of the amino acid sequence.

Controlled synthesis of peptide mixtures using mixed resins

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Benicia, CA, United States of America

Verena D Huebner