:Sunepitron
{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = 1-
| image = Sunepitron.png
| image_class = skin-invert-image
| width =
| tradename =
| pregnancy_category =
| legal_status =
| routes_of_administration = Oral
| bioavailability =
| metabolism =
| elimination_half-life =
| excretion =
| index2_label = HCl
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 131831-03-3
| CAS_number2_Ref = {{cascite|correct|CAS}}
| CAS_number2 = 148408-65-5
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2GT50C8U60
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = 1NYW5HLO1E
| ATC_prefix = none
| ATC_suffix =
| PubChem = 9799246
| ChemSpiderID = 7975011
| KEGG = D02569
| ChEMBL = 380369
| synonyms = CP-93,393
| C=17 | H=23 | N=5 | O=2
| SMILES = O=C1N(C(=O)CC1)CC4CCC3N(CCN(c2ncccn2)C3)C4
}}
Sunepitron (developmental code name CP-93,393) is a combined 5-HT1A receptor agonist and α2-adrenergic receptor antagonist.{{cite journal | vauthors = Goodnick PJ | title = Psychopharmacology of depression in the next millennium | journal = CNS Spectrums | volume = 4 | issue = 7 | pages = 21–35 | date = July 1999 | pmid = 18438295 | doi = 10.1017/s1092852900011998 | s2cid = 28460185 }}{{cite book | vauthors = Stahl SM | title = Essential psychopharmacology: neuroscientific basis and practical application | publisher = Cambridge University Press | location = Cambridge, UK | year = 2000 | isbn = 0-521-64615-4 | url = https://archive.org/details/essentialpsychop00step| url-access = registration | page = [https://archive.org/details/essentialpsychop00step/page/265 265] }} It was previously under development by Pfizer for the treatment of depression and anxiety.{{cite book | vauthors = Kaplan EP, Turkington C | title = Making the antidepressant decision: how to choose the right treatment option for you and your loved ones | publisher = Contemporary Books | location = Chicago, Ill | year = 2001 | isbn = 0-7373-0417-0 | url = https://books.google.com/books?id=qVtvcsUy2U8C&pg=PA218}} It made it to phase III clinical trials before being discontinued.
Chemistry
=Synthesis=
The synthesis starts by conversion of the pyridine dicarboxylic acid (1) to its acid chloride; rxn with MeOH then affords the ester (2). Catalytic hydrogenation serves to reduce the pyridine ring to a piperidine of undefined stereochemistry (3). Alkylation of this intermediate with chloroacetonitrile affords (4). Treatment of that intermediate with Raney nickel reduces the cyano group to the corresponding primary amine; this product then undergoes an internal ester-amine interchange to yield the cyclized lactam (5). LAH serves to reduce the lactam to an amine; the ester on the other ring is reduced to a carbinol in the process, affording the aminoalcohol (7). The basic function is next alkylated with 2-chloropyrimidine (7). Rxn of the alcoholin (8) with MsCl leads to the mesylate; that group is next displaced by sodium azide (9); the azide group is next reduced to the primary amine. Resolution of this product as its mandelate salt then yields (10) as a single enantiomer. Rxn of that product with succinic anhydride converts the pendant amine to a succinimide, affording the anxiolytic agent sunepitron (1).
See also
References
{{Reflist}}
{{Antidepressants}}
{{Anxiolytics}}
{{Adrenergic receptor modulators}}
{{Serotonin receptor modulators}}