Monkey Business
Mar24

Monkey Business

This message came to me from Linda Wang, who is currently attending the ACS national meeting in San Francisco. We'll look for Linda's famous meeting slideshow when she returns. Until then, we'll have to go bananas over this single pic: Earlier this week, I spotted this ape handing out Post-it notes to chemists outside the convention center. Charles Wolfus, ape and founder of the San Francisco-based company Zinali, was promoting his software tool Slideboxx to speed the creation of slide presentations. Hey, whatever...

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Liveblogging 1st Disclosures of Drug Candidates
Mar21

Liveblogging 1st Disclosures of Drug Candidates

UPDATE April 2: If you read this coverage please tell us what you thought about it here or in the comments. 1:26:15 PM: I'm @ Moscone Ctr in San Fran. T minus half hour to unveiling of new drug candidate structures. #acsmedi #acs_sf1:37:35 PM: A hearty welcome to any readers of Totally Synthetic @Totsyn #acsmedi2:01:50 PM: 1st: Albert J. Robichaud-of Lundbeck-on Pfizer's $PFE SAM-531, 5-HT6 antagonist for schizophrenia, Alzheimer's #acsmedi #acs_sf2:02:53 PM: Alzheimer's therapies today- palliative. Modulate eiether acetylcholine, glutamate #acsmedi #acs_sf2:04:58 PM: ~45 million ppl with ALzheimer's worldwide- patients have probs w learning,memory, reasoning #acsmedi #acs_sf2:06:33 PM: 5HT6- 1 of 14 serotonin receptors- a G-protein coupled receptor #acsmedi #acs_sf2:07:00 PM: block 5HT6- boosts levels of glutamate, acetylcholine neurotransmission in brain areas assoc w/learning, memory #acsmedi #acs_sf2:09:37 PM: focus has been indole, azaindoles #acsmedi #acs_sf2:09:47 PM: http://twitpic.com/1a3b3v - Lead2:12:17 PM: SAR: aryl sulfonyl groups req'd for activity. Most substitution not good on indole NH. #acswmedi #acs_sf2:15:13 PM: http://twitpic.com/1a3c9x - 5312:16:59 PM: SAM-531 enhances memory retention in rodents in a test called novel object recognition #acsmedi #acs_sf2:18:46 PM: SAM-531 potent selective 5HT6 antagonist. In phase II clinical development in patients with Alzheimer's #acsmedi #acs_sf2:21:00 PM: Q&A: what is brain to plasma ratio? speaker says less than 25%. But high enough for efficacy2:22:20 PM: pKa of the amine in metabolites? HERG inhibition? pKa wasn't known. No issues with HERG.2:22:37 PM: Next: Thomas Simpson of AstraZeneca $AZN on AZD2624, NK3 receptor antagonist to test NK3 hypothesis in schizophrenia #acsmedi #acs_sf2:22:46 PM: Astrazeneca on Twitter @AstraZenecaUS2:23:22 PM: Schizophrenia: 2.2 million people in US have it #acsmedi #acs_sf2:23:43 PM: Schiz. drugs (many are dopamine receptor antagonists) aren't equally effective @ treating all symptoms #acsmedi #acs_sf2:24:49 PM: NK3 blockers adjust dopamine levels by indirect mechanism- new opportunities #acsmedi #acs_sf2:25:41 PM: Phase II studies on osanetant and talnetant- NK3r blockers- precedents in clinic #acsmedi #acs_sf2:27:24 PM: both osenetant and talnetant are no longer in development- but support idea of NK3 #acsmedi #acs_sf2:28:50 PM: Talnetant is a more druglike structure than osanetant #acsmedi #acs_sf2:29:55 PM: Improve solubility and plasma protein binding of talnetant. A poster later today will outline early chem strategy. #acsmedi #acs_sf2:32:32 PM: http://twitpic.com/1a3g8v - T2:33:19 PM: http://twitpic.com/1a3gfd - O2:33:42 PM: Patnent #s WO2006130080, 137789, WO200703528 #acsmedi, #acs_sf2:35:44 PM: Sulfonate ester - this path leads to clinical candidate #acsmedi #acs_sf stability was an issue-hydrolysis2:37:31 PM: http://twitpic.com/1a3hcu - Sulf es2:38:49 PM: Alkylsulfonylamino groups- dramatic improvement in stability #acsmedi #acs_sf2:39:52 PM: 2624- gerbil brain/plasma: 0.21 #acsmedi #acs_sf2:40:12 PM: http://twitpic.com/1a3hyj - 26242:43:40 PM: Comparing a sulfoxide, AZD9122: half life (h): 2.8 rat, 6.7 dog. 2624 is better: 3.2 rat, 9.something in dog #acsmedi #acs_sf2:45:22 PM: in monkeys: AZD2624...

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