DNAprint Genomics (DNAG)

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Biofrontera info

http://64.233.179.104/search?q=cache:D2iUAfOY9hEJ:www.biomedcentral.com/content/pdf/cd-496691.pdf+bi...

Novel 4-(thioxanthen-9-ylidene)piperidines and their selenoxanthene and acridine analogs useful as selective 5-HT2BantagonistsBIOFRONTERA PHARMACEUTICALS GMBH (Lubbert H, Ullmer C,Bellott E, Froimowitz M, Gordon D) WO-03035646, 01 May 2003 Novel 4-(thioxanthen-9-ylidene)piperidines and their selenoxanthene and acridine analogs, a process for their preparation and their use as 5-HT2Bantagonists, in particular for the treatment of migraine, hypertension, gastrointestinal disease, gastric motility disorders, irritable bowel syndrome, restenosis, asthma, obstructive airway disease, bronchial pulmonary dysplasia, prostate hyperplasia, priapism and pain, are claimed. It is disclosed that the compounds are selective 5-HT2Bantagonists, demonstrating in vitro pKivalues of 11.06 (the specified compound) to 9.13 when tested in a 5-HT2Breceptor binding assay using HEK293 cells according to the method of Schmuck et al (Eur J Neurosci (1996) 8(5):959-967). The compounds demonstrated in vitropKivalues of 10.37 to 7.43 when tested in 5-HT2A, 5-HT2C andhistamine H1receptor binding assays. The results are presented in a table. It is also stated that the compounds act as selective antagonists in a functional 5-HT2Breceptor assay with rat stomach muscle, but no data are presented. The syntheses of five compounds are exemplified. The specified compound is 4-(1,6-dimethoxy-thioxanthen-9-yliden)-1-methylpiperidine, which is one of over 20 compounds specifically claimed. Reaction schemes are presented. SNCH3OCH3OCH3WO-03035646(Biofrontera Pharmaceuticals)

Current Opinion Biofrontera is a spin-off from the University of Mainz (Germany) that linked up with Janssen to explore the modulation of nicotinic ACh (nACh) receptors in Alzheimer's disease, a follow-up on the research that Biofrontera's founder, Dr Maelicke, performed on galantamine. Since then the young German company has moved to Leverkusen, Germany, and has changed and broadened its focus. Working with at least one co-inventor from Pharm-Eco Laboratories in Lexington, MA, USA, Biofrontera has carried out thorough studies on their compounds, even drawing up SARs by investigating which substituents determine 5-HT2Baffinities, and which one is responsible for undesired binding to the H1receptor. The 5-HT2Breceptor is the predominant 5-HT2receptor in the vasculature, and has been investigated by others as a target for migraine therapeutics, without much success in the clinic. It might be that the restenosis and gastrointestinal claims are more promising for this interesting family of compounds.