Piroheptine

Piroheptine
Clinical data
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	In general: ℞ (Prescription only);
Identifiers
	IUPAC name 3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-1-ethyl-2-methylpyrrolidine;
CAS Number	16378-21-5; HCl: 16378-22-6 ;
PubChem CID	4854;
ChemSpider	4688;
UNII	AR6Y753ARL; HCl: 4ZM573199N ;
KEGG	D01231 ;
ChEBI	CHEBI:135287;
CompTox Dashboard (EPA)	DTXSID30864672 ;
Chemical and physical data
Formula	C22H25N
Molar mass	303.449 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCN1CCC(=C2C3=CC=CC=C3CCC4=CC=CC=C42)C1C;
	InChI InChI=1S/C22H25N/c1-3-23-15-14-19(16(23)2)22-20-10-6-4-8-17(20)12-13-18-9-5-7-11-21(18)22/h4-11,16H,3,12-15H2,1-2H3; Key:NKJQZSDCCLDOQH-UHFFFAOYSA-N;
	(verify)

Piroheptine (brand name Trimol) is an anticholinergic and antihistamine used as an antiparkinsonian agent.

Piroheptine was observed to prevent the reuptake of dopamine and is therefore a DRI.^[1]^[2]

Piroheptine comes from a family of drugs that includes pridefine and etifelmine.

Synthesis

A mixture of 2.6g of 5-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene, PC1712685 (1), 0.34g MeCN, 5.2g PhCl and 2.1g stannic chloride (SnCl4) was heated in a closed vessel for 4 hr. After work-up there was obtained 1.1g of 2-methyl-3-(10,11-dihydro-5H-dibenzo[a,d] cycloheptene-5-ylidene)-1-pyrroline [16378-14-6] (2). Quaternization of the product with ethyl iodide affords the alkyl immonium ion, PC29938260 (3). Reduction of the Schiff base with sodium borohydride then affords the product, piroheptine (4).^[3]^[4]

References

^ Saitoh T (February 1988). "Suppression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in mouse brain by piroheptine and trihexyphenidyl". Journal of the Neurological Sciences. 83 (2–3): 161–166. doi:10.1016/0022-510X(88)90065-2. PMID 3258627. S2CID 25230405.
^ Ohashi T, Akita H, Tamura T, Noda K, Honda F (June 1972). "Effect of piroheptine, a new antiparkinson drug, on dopamine uptake into synaptosomes from corpus striatum of rat brain". Arzneimittel-Forschung. 22 (6): 966–972. PMID 5068358.
^ Yoshio Deguchi, Naomichi Kato, Hiroshi Nojima, U.S. patent 3,454,595 (1969 to Fujisawa Pharmaceutical Co).
^ Umio, S., Hitomi, M., Nojima, H., Kumadaki, N., Ueda, I., Kanaya, T., Deguchi, Y. (September 1972). "Synthesis and pharmacological properties of 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1,2-dialkylpyrrolidine derivatives". Journal of Medicinal Chemistry. 15 (9): 891–894. doi:10.1021/jm00279a004. PMID 4403249.

[1] Saitoh T (February 1988). "Suppression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in mouse brain by piroheptine and trihexyphenidyl". Journal of the Neurological Sciences. 83 (2–3): 161–166. doi:10.1016/0022-510X(88)90065-2. PMID 3258627. S2CID 25230405.

[pmid5068358-2] Ohashi T, Akita H, Tamura T, Noda K, Honda F (June 1972). "Effect of piroheptine, a new antiparkinson drug, on dopamine uptake into synaptosomes from corpus striatum of rat brain". Arzneimittel-Forschung. 22 (6): 966–972. PMID 5068358.

[3] Yoshio Deguchi, Naomichi Kato, Hiroshi Nojima, U.S. patent 3,454,595 (1969 to Fujisawa Pharmaceutical Co).

[4] Umio, S., Hitomi, M., Nojima, H., Kumadaki, N., Ueda, I., Kanaya, T., Deguchi, Y. (September 1972). "Synthesis and pharmacological properties of 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1,2-dialkylpyrrolidine derivatives". Journal of Medicinal Chemistry. 15 (9): 891–894. doi:10.1021/jm00279a004. PMID 4403249.

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