Sunepitron

Sunepitron
Clinical data
Other names	CP-93,393
Routes of; administration	Oral
ATC code	none;
Identifiers
	IUPAC name 1-{[2-(pyrimidin-2-yl)octahydro-2H-pyrido[1,2-a]pyrazin-7-yl]methyl}pyrrolidine-2,5-dione;
CAS Number	131831-03-3 ; HCl: 148408-65-5 ;
PubChem CID	9799246;
ChemSpider	7975011;
UNII	2GT50C8U60; HCl: 1NYW5HLO1E ;
KEGG	D02569;
ChEMBL	ChEMBL380369;
Chemical and physical data
Formula	C17H23N5O2
Molar mass	329.404 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C1N(C(=O)CC1)CC4CCC3N(CCN(c2ncccn2)C3)C4;

Sunepitron (developmental code name CP-93,393) is a combined 5-HT_1A receptor agonist and α₂-adrenergic receptor antagonist.^[1]^[2] It was previously under development by Pfizer for the treatment of depression and anxiety.^[3] It made it to phase III clinical trials before being discontinued.^[2]^[3]

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).

References

^ Goodnick PJ (July 1999). "Psychopharmacology of depression in the next millennium". CNS Spectrums. 4 (7): 21–35. doi:10.1017/s1092852900011998. PMID 18438295. S2CID 28460185.
^ ^a ^b Stahl SM (2000). Essential psychopharmacology: neuroscientific basis and practical application. Cambridge, UK: Cambridge University Press. p. 265. ISBN 0-521-64615-4.
^ ^a ^b Kaplan EP, Turkington C (2001). Making the antidepressant decision: how to choose the right treatment option for you and your loved ones. Chicago, Ill: Contemporary Books. ISBN 0-7373-0417-0.

[pmid18438295-1] Goodnick PJ (July 1999). "Psychopharmacology of depression in the next millennium". CNS Spectrums. 4 (7): 21–35. doi:10.1017/s1092852900011998. PMID 18438295. S2CID 28460185.

[isbn0-521-64615-4-2] Stahl SM (2000). Essential psychopharmacology: neuroscientific basis and practical application. Cambridge, UK: Cambridge University Press. p. 265. ISBN 0-521-64615-4.

[isbn0-7373-0417-0-3] Kaplan EP, Turkington C (2001). Making the antidepressant decision: how to choose the right treatment option for you and your loved ones. Chicago, Ill: Contemporary Books. ISBN 0-7373-0417-0.

[1]

[2]

[3]

v t e Anxiolytics (N05B)
5-HT_1ARTooltip 5-HT1A receptor agonists	Buspirone Gepirone Tandospirone
GABA_ARTooltip GABAA receptor PAMsTooltip positive allosteric modulators	Benzodiazepines: Adinazolam Alprazolam Bromazepam Camazepam Chlordiazepoxide Clobazam Clonazepam Clorazepate Clotiazepam Cloxazolam Diazepam^# Ethyl loflazepate Etizolam Fludiazepam Halazepam Ketazolam Lorazepam^# Medazepam Nordazepam Oxazepam Pinazepam Prazepam; Others: Alpidem^‡ Barbiturates (e.g., phenobarbital) Carbamates (e.g., meprobamate) Carisoprodol Chlormezanone^‡ Ethanol (alcohol) Etifoxine
Hypnotics	Zopiclone
Gabapentinoids (α₂δ VDCC blockers)	Gabapentin Gabapentin enacarbil Phenibut Pregabalin
Antidepressants	SSRIsTooltip Selective serotonin reuptake inhibitors (e.g., escitalopram) SNRIsTooltip Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) SARIsTooltip Serotonin antagonist and reuptake inhibitors (e.g., trazodone) TCAsTooltip Tricyclic antidepressants (e.g., clomipramine^#) TeCAsTooltip Tetracyclic antidepressants (e.g., mirtazapine) MAOIsTooltip Monoamine oxidase inhibitors (e.g., phenelzine); Others: Agomelatine Bupropion Tianeptine Vilazodone Vortioxetine
Antipsychotics	Quetiapine Flupentixol
Sympatholytics (Antiadrenergics)	Alpha-1 blockers (e.g., prazosin) Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine) Beta blockers (e.g., propranolol)
Others	Benzoctamine Cycloserine Fabomotizole Hydroxyzine Lorpiprazole Mebicar Mepiprazole Nicotine Opipramol Oxaflozane^‡ Phenaglycodol Phenibut Picamilon Selank Tiagabine Tofisopam Validolum
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

Chemistry

Synthesis

See also

References