ritanserin ritanserin ritanserin, also known by its developmental code name r-55667, is a serotonin antagonist medication described as an anxiolytic, antidepressant, antiparkinsonian agent, and antihypertensive agent. it was chiefly investigated as a drug to treat insomnia, especially to enhance sleep quality by significantly increasing slow wave sleep by virtue of potent and concomitant 5ht2a and 5ht2c antagonism ritanserinclinical dataother namesr-55667; r55667; tisertonatc codenoneidentifiers iupac name 6-piperidin-1-yl]ethyl]-7-methyl-thiazolopyrimidin-5-one cas number87051-43-2 ypubchem cid5074iuphar/bps97chemspider4896 nunii145tfv465schebichebi:64195 nchemblchembl267777 ncomptox dashboard (epa)dtxsid9042594 echa infocard100.163.772 chemical and physical dataformulac27h25f2n3osmolar mass477.57 g·mol−13d model (jsmol)interactive image smiles cc1=c(c(=o)n2c=csc2=n1)ccn3ccc(=c(c4=cc=c(c=c4)f)c5=cc=c(c=c5)f)cc3 inchi inchi=1s/c27h25f2n3os/c1-18-24(26(33)32-16-17-34-27(32)30-18)12-15-31-13-10-21(11-14-31)25(19-2-6-22(28)7-3-19)20-4-8-23(29)9-5-20/h2-9,16-17h,10-15h2,1h3 nkey:juqltpcyufpyke-uhfffaoysa-n n ny (what is this?) (verify) it was never marketed for medical use due to safety problems but is currently used in scientific research. some of the safety liabilities that lead to its discontinuation for the treatment of insomnia has led to its potential repurposing in the field of oncology. specifically, ritanserin acts as a potent inhibitor of diacylglycerol kinase alpha (dgkα). as such, it may be used to treat certain types of glioblastoma and melanoma. it has also been used as a reference compound to identify putatively more selective and potent dgkα inhibitors to treat these forms of cancer as well as possibly others. additionally, ritanserin blocks c-raf activation and induces apoptotic cell death of non–small cell lung cancer and small cell lung cancer cells. pharmacology pharmacodynamics ritanserin acts as a selective 5-ht2a (ki = 0.45 nm) and 5-ht2c receptor (ki = 0.71 nm) antagonist. it has relatively low affinity for the h1, d2, α1-adrenergic, and α2-adrenergic receptors (39-, 77-, 107-, and 166-fold lower relative to 5-ht2a, respectively). the affinity of ritanserin for the 5-ht1a receptor is less than 1 μm. in addition to its affinity for the 5-ht2a and 5-ht2c receptors, ritanserin also binds to and antagonizes the 5-ht1d, 5-ht2b, 5-ht5a, 5-ht6, and 5-ht7 receptors. history the atypical antipsychotic risperidone was developed from ritanserin. society and culture names ritanserin is the generic name of the drug and its inn, usan, and ban. it is also known by its developmental code name r-55667. availability ritanserin was never approved or marketed for medical use. research ritanserin was tested in clinical trials for depression, anxiety, schizophrenia, and migraine. it was also found to improve sleep in human volunteers. synthesis synthesis: patents: aminothiazole (2-thiazolamine) (1) is condensed with 2-acetylbutyrolactone (2) under ds-trap until the water has separated. condensation of this β-keto lactone can be visualized to involve initial attack on the reactive butyrolactone by the primary nitrogen; cyclodehydration of that hypothetical intermediate 3 gives 6-(2-hydroxyethyl)-7-methyl-thiazolopyrimidin-5-one, cid:82612453 (4). halogenation of the terminal alcohol with phosphorus oxychloride then yields 6-(2-chloroethyl)- 7-methyl-5h-thiazolopyrimidin-5-one, (5). alkylation with 4-(bis(4-fluorophenyl)methylene)piperidine, (6) would complete the synthesis of ritanserin (7).