Cyprolidol

Cyprolidol

Clinical data
Other names	IN 1060
Identifiers
IUPAC name diphenyl-(2-pyridin-4-ylcyclopropyl)methanol
CAS Number	7433-09-2 [2364-72-9] (hydrochloride), [4904-00-1] (±)-trans/(1RS,2SR)
PubChem CID	23287
ChemSpider	21778
UNII	7UQN2OJ7SM
ChEMBL	ChEMBL2110906
Chemical and physical data
Formula	C21H19NO
Molar mass	301.389 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1C(C1C(C2=CC=CC=C2)(C3=CC=CC=C3)O)C4=CC=NC=C4
InChI InChI=1S/C21H19NO/c23-21(17-7-3-1-4-8-17,18-9-5-2-6-10-18)20-15-19(20)16-11-13-22-14-12-16/h1-14,19-20,23H,15H2 Key:KPUSUIKQQCFQCX-UHFFFAOYSA-N

Cyprolidol is an experimental antidepressant drug that was developed by Neisler Laboratories in the 1960s. ^[1] It was never approved for human use.

In preclinical studies, cyprolidol demonstrated antidepressant effects in animal models that were qualitatively similar to those of imipramine, a well-established tricyclic antidepressant. ^{[2] [3]} However, clinical observations indicated that cyprolidol was less effective than imipramine in humans. ^[4] Pharmacologically, cyprolidol also exhibited cardiovascular effects, such as blocking the tyramine-induced rise in blood pressure in anesthetized dogs while potentiating this response in conscious dogs, suggesting a complex interaction with adrenergic systems. ^[5]

Its synthesis is similar to tranylcypromine, a monoamine oxidase inhibitor.

Synthesis

Cyprolidol synthesis

The cyclopropanation reaction between 4-vinylpyridine and ethyl diazoacetate affords ethyl 2-pyridin-4-ylcyclopropane-1-carboxylate. For steric reasons, the trans isomer is the thermodynamically favoured racemer, although epimerization may be needed to convert the cis isomer to the needed trans isomer. The Grignard reaction of two equivalents of phenylmagnesium bromide with the electrophilic ester completes the synthesis of cyprolidol. ^{[6] [7] [8] [9]}

References

1. "Cyprolidol hydrochloride". Inxight Drugs. National Center for Advancing Translational Sciences (NCATS), U.S. National Institutes of Health.
2. Brown ML, Gershon S, Korol B (1966). "Some pharmacological effects of a new potential antidepressant cyprolidol (IN-1060) compared with imipramine". Medicina et Pharmacologia Experimentalis. International Journal of Experimental Medicine. 15 (4): 329–43. doi:10.1159/000135886. PMID   6012765.
3. Miller L, Napoli M, O'Dell TB (April 1967). "Pharmacological evaluation of a potential psychotherapeutic agent: cyprolidol, a pyridylcyclopropane derivative". Archives Internationales de Pharmacodynamie et de Therapie. 166 (2): 313–323. PMID   4963240.
4. Hekimian LJ, Gershon S, Floyd A (June 1969). "Cyprolidol and imipramine: a double-blind controlled study in endogenous depression". Arzneimittel-Forschung. 19 (6): 955–956. PMID   4896165.
5. Korol B, Brown ML, Sletten IW (November 1966). "Effects of a new antidepressant cyprolidol (IN-1060) upon the blood pressure responses to autonomic drugs in conscious dogs". Current Therapeutic Research, Clinical and Experimental. 8 (11): 543–548. PMID   4963159.
6. Gray AP, Kraus H (February 1966). "Cyclopropylpyridines. Synthesis and Electronic Interaction 1". The Journal of Organic Chemistry. 31 (2): 399–405. doi:10.1021/jo01340a013.
7. "BE649145". Neisler Lab. 1964.
8. "AT250957B". 1966.
9. Lednicer D, Mitscher L. The Organic Chemistry of Drug Synthesis. Vol. 2. p. 31.

 This article incorporates public domain material from Cyprolidol hydrochloride. United States government . Retrieved 27 May 2025.