ACADIA Pharmaceuticals Inc.

About: ACADIA Pharmaceuticals Inc. is a company organization based out in San Diego, California, United States. It is known for research contribution in the topics: Pimavanserin & Receptor. The organization has 260 authors who have published 276 publications receiving 8418 citations.

Cleft molecules as organocatalysts in an asymmetric hetero-Diels-Alder reaction

Abstract: The synthesis and application of chiral carbocyclic cleft molecules derived from 2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-diene in the hetero-Diels-Alder reaction of benzaldehydes and aminodiene 14 is presented. Catalysis by single hydrogen-bond activation gave up to 52% ee.

The effects of food on the pharmacokinetics of a formulated ACP-103 tablet in healthy volunteers.

Abstract: A CP-103, N-(4-flurophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy) phenylmethyl)carbamide (2R,3R)-dihydroxybutanedioate (2:1), is a potent inverse agonist at serotonin 5-HT2A receptors currently being developed as a novel antipsychotic drug. In a phase I clinical study, ACP103 was found to be safe and well tolerated at single oral doses ranging from 20 to 300 mg and multiple doses up to and including 100 mg daily for 14 days in healthy volunteers. The first pharmacokinetic study in humans was conducted using an oral solution. Administration of this oral solution resulted in a bitter taste and was not well tolerated. In that first study, single doses greater than 50 mg were administered nasogastrically to avoid the local intolerance. ACP-103 was administered in powder-filled capsules for the multiple-dose study. Subsequently, ACP-103 was formulated in an immediate-release coated tablet. The purpose of the present study was to compare the pharmacokinetics after administration of the formulated coated tablet to those after administration of the solution of ACP-103. Furthermore, the effects of food on the pharmacokinetics of ACP-103 after a single oral administration were evaluated in healthy male subjects.

Nighttime Sleep and Daytime Sleepiness Improved With Pimavanserin During Treatment of Parkinson's Disease Psychosis.

Abstract: Introduction Impaired nocturnal sleep and excessive daytime sleepiness are common problems for patients with Parkinson's disease, and patients with Parkinson's disease with sleep dysfunction are 5 times more likely to experience psychotic symptoms. Pimavanserin, a 5-HT2A inverse agonist approved to treat Parkinson's disease psychosis, may improve sleep quality in patients with Parkinson's disease experiencing sleep disturbances. Methods Scales for Outcomes in Parkinson's Disease nighttime sleep (SCOPA-NS) and SCOPA-daytime sleepiness (DS) data obtained during 2 double-blind placebo-controlled studies of pimavanserin in persons with Parkinson's disease psychosis were evaluated. Data from the placebo and pimavanserin 34 mg groups in the 2 studies were pooled to provide further information on the effect of pimavanserin 34 mg on sleep. Additional analyses on the pooled study data were performed on participants with significantly impaired nighttime sleep and daytime sleepiness, defined as SCOPA-NS ≥7 and SCOPA-DS ≥5, respectively. Results In the pooled analysis, treatment effects, expressed as least squares mean reductions in SCOPA-NS at week 6, were -1.4 for pimavanserin 34 mg and -0.5 for placebo. At week 6, the decrease from baseline in SCOPA-DS for the pimavanserin 34 mg group was -1.7 and -1.2 for the placebo group (P = 0.108). When evaluating participants with impaired nighttime sleep and daytime sleepiness at baseline, the SCOPA-NS score change was -4.4 for the pimavanserin 34 mg group and -2.3 for the placebo group (P = 0.002), whereas the SCOPA-DS change was -2.9 and -1.9 for the pimavanserin 34 mg and placebo groups (P = 0.120), respectively. Conclusion The data from the trials suggest that nighttime sleep improved with administration of pimavanserin, a novel 5-HT2A receptor inverse agonist/antagonist.

Asymmetric synthesis of a tricyclic benzofuran motif: a privileged core structure in biologically active molecules

Abstract: An efficient synthetic strategy for the asymmetric synthesis of a hexahydrodibenzofuran core structure, with a quaternary stereogenic center, emerges by employing a chiral reduction using Corey's (S)-Me-CBS-oxazaborolidine reagent followed by a Mitsunobu reaction to set the stereochemistry. A Pd-mediated intramolecular Heck reaction concludes the tricyclic core structure. Finally, a Pd/C catalyzed reduction yields the target molecule in 21% overall yield over 6 steps.