Drug Candidate Structures Revealed At #ACSAnaheim
Mar27

Drug Candidate Structures Revealed At #ACSAnaheim

1PM Pacific: There's one hour left before chemists will pack a ballroom in Anaheim to see potential new drugs' structures unveiled for the first time. Watch this space for updates. 2:39PM Pacific: CEP-26401 This drug candidate now has a name: irdabisant company: Cephalon meant to treat: deficits in cognition and/or attention in diseases such as Alzheimer's and schizophrenia mode of action: inverse agonist of histamine H3 receptor, which regulates several neurotransmitter pathways involved in cognition, attention, memory medicinal chemistry tidbits: Cephalon's goal was to bring a high quality compound to the clinic to define the utility, if any, of H3 antagonists for these indications. The team studied compounds in this area that failed. Among the things they learned was that several adverse events could be tied to drug candidates' lipophilicity. So the team prioritized lipophilicity and other such characteristics in its discovery workflow. status in the pipeline: completing Phase I in the beginning of April 2011, advancing to Phase II structure coming soon! UPDATED 3/29 with structure: 3:16PM Pacific: BMS-663068 company: Bristol-Myers Squibb meant to treat: HIV mode of action: inhibits HIV attachment to host cells by binding to the viral envelope gp120 protein and interfering with its attachment to host CD4 receptors medicinal chemistry tidbits: potency and getting the drug candidates to reach the bloodstream efficiently were key. Replacing a methoxy group on with heterocycles, such as triazoles, gave a big boost in potency. status in the pipeline: Completed Phase IIa clinical trials. Phase IIb studies are planned for later this year. 4:24PM Pacific:LX1031 company: Lexicon meant to treat: irritable bowel syndrome mode of action: blocks a subtype of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, in the gut. medicinal chemistry tidbits: Lexicon started their medchem program with an open mind. They could have made a molecule that was exquisitely selective for the subtype of tryptophan hydroxylase in the gut, they could avoid hitting the other subtype by making their molecule stay out of the brain, or both. They ultimately ended up using the latter strategy, making molecules slightly on the heavy side (above 500 or 550 molecular weight) and adding groups like a carboxylic acid, that tend to keep things out of the brain. status in the pipeline: Completed Phase IIa clinical trials. 5:30PM Pacific: MK-0893 company: Merck meant to treat: type 2 diabetes mode of action: blocks the receptor for the hormone glucagon. Glucagon is released by the pancreas in response to falling glucose levels. medicinal chemistry tidbits: Merck kept several chemical scaffolds in play during this research program. But the team's big breakthrough was adding a methyl group to the benzylic position of a...

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First Time Drug Disclosures at #ACSAnaheim
Mar25

First Time Drug Disclosures at #ACSAnaheim

Medicinal chemists, it's that time of year once again. Time for the ACS National Meeting, and the accompanying symposium where drug companies reveal the structures of drug candidates in clinical trials for the first time. I'll be on the ground in Anaheim and will be posting from that session (which lasts from 2PM-5PM Pacific Sunday the 27th) and others. Here is the Anaheim Division of Medicinal Chemistry program (pdf). And here is the list of disclosures: Discovery and characterization of CEP-26401: A potent, selective histamine H3 receptor inverse agonist: R. Hudkins, Cephalon Discovery of BMS-663068, an HIV attachment inhibitor for the treatment of HIV-1: J. Kadow, Bristol-Myers Squibb Discovery and development of LX1031, a novel serotonin synthesis inhibitor for the treatment of irritable bowel syndrome: A. Main, Lexicon Discovery of MK-0893: A glucagon receptor antagonist for the treatment of type II diabetes: E. Parmee, Merck Discovery of ELND006: A selective γ-secretase inhibitor: G. Probst,...

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