Elzasonan

Elzasonan
Clinical data
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	In general: uncontrolled;
Identifiers
	IUPAC name 4-(3,4-dichlorophenyl)-2-[2-(4-methylpiperazin-1-yl)-benzylidene]-thiomorpholin-3-one;
CAS Number	361343-19-3 ; HCl: 220322-05-4 ;
PubChem CID	19544192; HCl: 6914152;
ChemSpider	5290108;
UNII	933PJL964R; HCl: X38F62RR8L ;
Chemical and physical data
Formula	C22H23Cl2N3OS
Molar mass	448.41 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Clc4c(Cl)cc(N1C(=O)C(\SCC1)=C\c3ccccc3N2CCN(C)CC2)cc4;
	InChI InChI=1S/C22H23Cl2N3OS/c1-25-8-10-26(11-9-25)20-5-3-2-4-16(20)14-21-22(28)27(12-13-29-21)17-6-7-18(23)19(24)15-17/h2-7,14-15H,8-13H2,1H3/b21-14-; Key:LHYMPSWMHXUWSK-STZFKDTASA-N;
	(verify)

Elzasonan (CP-448,187) is a selective 5-HT_1B and 5-HT_1D receptor antagonist that was under development by Pfizer for the treatment of depression but was discontinued, possibly due to poor efficacy.^[1]^[2]^[3]^[4]^[5] By preferentially blocking 5-HT_1B and 5-HT_1D autoreceptors, elzasonan is thought to enhance serotonergic innervations originating from the raphe nucleus, thereby improving signaling to limbic regions like the hippocampus and prefrontal cortex and ultimately resulting in antidepressant effects.^[3]

Synthesis

The aldol condensation of 2-(4-Methylpiperazino)benzaldehyde [85803-62-9] (1) with 4-(3,4-dichlorophenyl)thiomorpholin-3-one [205683-35-8] (2) gives Elzasonsan (3).

References

^ Vela JM, Buschmann H, Holenz J, Párraga A, Torrens A (2007). Antidepressants, Antipsychotics, Anxiolytics: From Chemistry and Pharmacology to Clinical Application. Weinheim: Wiley-VCH. ISBN 978-3-527-31058-6.
^ Stahl SM (2008). Stahl's essential psychopharmacology: neuroscientific basis and practical applications. Cambridge, UK: Cambridge University Press. ISBN 978-0-521-85702-4.
^ ^a ^b Dawson LA, Bromidge SM (August 2008). "5-HT1 receptor augmentation strategies as enhanced efficacy: therapeutics for psychiatric disorders". Current Topics in Medicinal Chemistry. 8 (12): 1008–23. doi:10.2174/156802608785161439. PMID 18691129.
^ Norman P (2002). "Pfizer, Inc.: analysis of patenting 1998 – 2001". Expert Opinion on Therapeutic Patents. 12 (5): 725–732. doi:10.1517/13543776.12.5.725. S2CID 84645020.
^ Kirchhoff VD, Nguyen HT, Soczynska JK, Woldeyohannes H, McIntyre RS (October 2009). "Discontinued psychiatric drugs in 2008". Expert Opinion on Investigational Drugs. 18 (10): 1431–43. doi:10.1517/13543780903184591. PMID 19715445. S2CID 34201544.
^ Joseph P. Rainville, Terry G. Sinay, Stanley W. Walinsky, U.S. patent 6,608,195 (2003 to Pfizer Inc.).

[isbn3-527-31058-4-1] Vela JM, Buschmann H, Holenz J, Párraga A, Torrens A (2007). Antidepressants, Antipsychotics, Anxiolytics: From Chemistry and Pharmacology to Clinical Application. Weinheim: Wiley-VCH. ISBN 978-3-527-31058-6.

[isbn0-521-85702-3-2] Stahl SM (2008). Stahl's essential psychopharmacology: neuroscientific basis and practical applications. Cambridge, UK: Cambridge University Press. ISBN 978-0-521-85702-4.

[Dawson_2008-3] Dawson LA, Bromidge SM (August 2008). "5-HT1 receptor augmentation strategies as enhanced efficacy: therapeutics for psychiatric disorders". Current Topics in Medicinal Chemistry. 8 (12): 1008–23. doi:10.2174/156802608785161439. PMID 18691129.

[Norman_2002-4] Norman P (2002). "Pfizer, Inc.: analysis of patenting 1998 – 2001". Expert Opinion on Therapeutic Patents. 12 (5): 725–732. doi:10.1517/13543776.12.5.725. S2CID 84645020.

[urlDiscontinued_psychiatric_drugs_in_2008;_Expert_Opinion_on_Investigational_Drugs_-_18(10):Pages_1431-1443_-_Informa_Healthcare-5] Kirchhoff VD, Nguyen HT, Soczynska JK, Woldeyohannes H, McIntyre RS (October 2009). "Discontinued psychiatric drugs in 2008". Expert Opinion on Investigational Drugs. 18 (10): 1431–43. doi:10.1517/13543780903184591. PMID 19715445. S2CID 34201544.

[6] Joseph P. Rainville, Terry G. Sinay, Stanley W. Walinsky, U.S. patent 6,608,195 (2003 to Pfizer Inc.).

[1]

[2]

[3]

[4]

[5]

[6]

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

Synthesis

See also

References