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Droven results P r o j e c t g o a l : To prioritize leads from several related chemical series,each possessing comparable biological activity. D e t a i l s : Several series of lead compounds had comparable biological activity. The customer sought to prioritize and develop analogs based upon favorable metabolic characteristics, including half-life.
AMRI now offers in vitro metabolic tests to support lead optimization.
O u t c o m e : AMRI's scientists delivered the following results within two weeks: •
Ranked the in vitro metabolic stability of each series and derivatives relative toothers.
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Identified structural features within the classes consistent with improved metabolic stability, and reported these to the medicinal chemists for further analog design.
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21 Corporate Circle, P.O. Box 15098 Albany, NY 12212-5098 Phone: 518-464-0279 Fax:518-464-0289
[email protected] www.albmolecular.com
Identified the primary human metabolic enzyme isoform involved in the metabolism of the lead series, as well as the identity of the major metabolites formed.
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Identified the mouse as an appropriate animal model system that most closely represented the human metabolic pattern for this class of compounds.
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Identified that selected derivatives of the lead series did not significantly inhibit any of the major human liver cytochrome P450 enzymes.
F o l l o w - U p : Produced 10 mg of two human metabolites of interest within three weeks for further evaluation.
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• Metabolic Stability Assays • Metabolic Profiling Assays • Metabolite Production • CYP450 Isoform Analysis • CYP450 Inhibition Assays
Call AMRI today to learn how we can help your drug development efforts.
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craven results P r o j e c t g o a l : To prepare 16 kg of an intermediate in six weeks. D e t a i l s : The synthesis of the intermediate required three steps—a hydride reduction, hydrogenation of an aromatic ring, and tosylation of an alcohol. Some development work was needed. O u t c o m e : After conducting some process research, AMRI's chemical development team delivered the following results: • Modified work up of the first step, making it twice as productive. • Changed the catalyst in the hydrogenation, saving $14,000 and increasing the yield from 85% to 99%. • Increased the concentration of the third step, improving the productivity by 50%. • Delivered the product to the customer two weeks early.
Call AMRI today to learn how we can help your drug development efforts. 21 Corporate Circle, P.O. Box 15098 Albany, NY 12212-5098 Phone:518-464-0279 • Fax:518-464-0289
[email protected] • www.albmolecular.com
F o l l o w - l i p : The customer returned to AMRI with a request to synthesize 85 kg of the same compound. The starting material was ordered by the customer from an overseas supplier with an anticipated delivery that would leave eight weeks for the synthesis. The starting material arrived four weeks later than promised. Under a tight time frame, AMRI development scientists made improvements to the process that allowed this synthesis to be carried out at a price per kg that was 46% lower than the initial preparation. In addition, AMRI scientists delivered the desired 85 kg in six weeks, preventing a delay in the customer's program.
