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;
ChEMBL	ChEMBL2106077;
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]

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^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

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Synthesis

See also

References