Clemeprol

Clemeprol
Clinical data
Other names	BRL 14342
Identifiers
	IUPAC name 1-(3-chlorophenyl)-3-(dimethylamino)-1-phenylpropan-2-ol;
CAS Number	71827-56-0 ;
PubChem CID	10108256;
ChemSpider	64987;
UNII	R3TC4SEW5A;
ChEMBL	ChEMBL2106077;
CompTox Dashboard (EPA)	DTXSID90868035 ;
Chemical and physical data
Formula	C17H20ClNO
Molar mass	289.80 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN(C)CC(C(C1=CC=CC=C1)C2=CC(=CC=C2)Cl)O;
	InChI InChI=InChI=1S/C17H20ClNO/c1-19(2)12-16(20)17(13-7-4-3-5-8-13)14-9-6-10-15(18)11-14/h3-11,16-17,20H,12H2,1-2H3; Key:KGSABFQIAANNPS-UHFFFAOYSA-N;

Clemeprol is an serotonin–norepinephrine reuptake inhibitor (SNRI) antidepressant and anticholinergic agent.^[1]

It is an enantiomeric mixture of R and S isomers. Both isomers show similar pharmacological activity.^[2]^[3]

Synthesis

A synthetic pathway for clemeprol is disclosed: ^[4]^[5]^[6]^[7]^[8]

The Corey-Chaykovsky epoxidation between 3-chlorobenzophenone [1016-78-0] (1) and dimethylsulfoxonium methylide (Corey's reagent) [5367-24-8], gives 2-(3-chlorophenyl)-2-phenyloxirane [71827-53-7] (2). Further reaction with boron trifluoride etherate [109-63-7] gives m-chlorophenyl-phenylacetaldehyde, PC12549135 (3). A second Corey-Chaykovsky epoxidation gives 2-[(3-chlorophenyl)-phenylmethyl]oxirane, PC12549073 (4). Quenching with dimethylamine completes the synthesis of clemeprol (5).

References

^ Dictionary of Pharmacological Agents By C.R. Ganellin, David J. Triggle.
^ Clark MS, Johnson AM, McClelland GR, Nelson DR (December 1980). "Pharmacological and biochemical properties of BRL 14342, a novel potential antidepressant drug". Neuropharmacology. 19 (12): 1207–8. doi:10.1016/0028-3908(80)90203-8. PMID 7442949.
^ Koch, H., Drugs Future, 1983,8, 194.
^ Clark JA, Clark MS, Gardner DV, Gaster LM, Hadley MS, Miller D, et al. (November 1979). "Substituted 3-amino-1,1-diaryl-2-propanols as potential antidepressant agents". Journal of Medicinal Chemistry. 22 (11): 1373–9. doi:10.1021/jm00197a018. PMID 533885.
^ Anon., GB1448437 (1976-09-08 to Beecham Group Ltd).
^ Judith Ann Clark, US4101676 & US4113972 (1978 to Beecham Group PLC).
^ Judith Ann Clark, US4056630 (1977 to Beecham Group PLC).
^ CA1049530 idem Judith Ann Clark, US4028415 (1977 to Beecham Group PLC).

[1] Dictionary of Pharmacological Agents By C.R. Ganellin, David J. Triggle.

[Clark_1980-2] Clark MS, Johnson AM, McClelland GR, Nelson DR (December 1980). "Pharmacological and biochemical properties of BRL 14342, a novel potential antidepressant drug". Neuropharmacology. 19 (12): 1207–8. doi:10.1016/0028-3908(80)90203-8. PMID 7442949.

[3] Koch, H., Drugs Future, 1983,8, 194.

[Clark_1979-4] Clark JA, Clark MS, Gardner DV, Gaster LM, Hadley MS, Miller D, et al. (November 1979). "Substituted 3-amino-1,1-diaryl-2-propanols as potential antidepressant agents". Journal of Medicinal Chemistry. 22 (11): 1373–9. doi:10.1021/jm00197a018. PMID 533885.

[5] Anon., GB1448437 (1976-09-08 to Beecham Group Ltd).

[6] Judith Ann Clark, US4101676 & US4113972 (1978 to Beecham Group PLC).

[7] Judith Ann Clark, US4056630 (1977 to Beecham Group PLC).

[8] CA1049530 idem Judith Ann Clark, US4028415 (1977 to Beecham Group PLC).

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

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
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
Sympatholytics (Antiadrenergics)	Alpha-1 blockers (e.g., prazosin) Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine) Beta blockers (e.g., propranolol, atenolol, betaxolol, nadolol, oxprenolol, pindolol)
Others	Benzoctamine Cycloserine Fabomotizole Hydroxyzine Lorpiprazole Mebicar Mepiprazole Nicotine (tobacco) Opipramol Oxaflozane^‡ Phenaglycodol Phenibut Picamilon Selank Tiagabine Tofisopam Validolum
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

Neuropathic pain and fibromyalgia pharmacotherapies
Monoaminergics	SNRIsTooltip Serotonin–norepinephrine reuptake inhibitor (e.g., duloxetine, milnacipran) TCAsTooltip Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, dosulepin) Opioid MRIsTooltip monoamine reuptake inhibitors (e.g., tapentadol, tramadol)
Ion channel blockers	Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) Local anesthetics (e.g., lidocaine) Mexiletine TCAsTooltip Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, desipramine) Ziconotide
Others	Alpha lipoic acid Benfotiamine Botulinum toxin A Bupropion Cannabinoids (e.g., cannabis, dronabinol, nabilone) NMDA receptor antagonists (e.g., ketamine, dextromethorphan, methadone) Opioids (e.g., hydrocodone, morphine, oxycodone, methadone, buprenorphine, tramadol, tapentadol) Sodium oxybate (GHB)

Synthesis

See also

References