3595-11-7

Usage

Uses

Used in Pharmaceutical Industry:
Propylhexedrine is used as an adrenergic vasoconstrictor for the symptomatic relief of nasal congestion caused by common cold, allergic rhinitis, or sinusitis. It provides a local vasoconstrictive effect on nasal mucosa, reducing swelling and congestion.
Used in Over-the-counter Medications:
Propylhexedrine is used as an active ingredient in various over-the-counter nasal decongestant products, such as Dristan Inhaler (Whitehall-Robins), Benzedrex, Chp-depot, Cyclexedrine, Eggobesin, and Eventin. These products help alleviate nasal congestion and provide relief from respiratory discomfort.

World Health Organization (WHO)

Propylhexedrine, a sympathomimetic amine, has been widely available since 1949 in over-the-counter inhalants for nasal decongestion and in oral anorexic preparations. As dependence can occur and because abuse has been reported, propylhexedrine was subjected in 1986 to control under Schedule IV of the 1971 Convention on Psychotropic Substances. (Reference: (WHTAC2) 2nd Report of the WHO Expert Committee on Drug Dependence (IV), 729, , 1985)

Synthesis Reference(s)

Journal of the American Chemical Society, 80, p. 5270, 1958 DOI: 10.1021/ja01552a063

InChI:InChI=1/C10H21N/c1-9(11-2)8-10-6-4-3-5-7-10/h9-11H,3-8H2,1-2H3

Upstream product

• 123-39-7 N-Methylformamide 
• 64-18-6 formic acid 
• 103-78-6 4-cyclohexyl-butan-2-one 
• 99175-77-6 N-(2-cyclohexyl-1-methyl-ethyl)-formamide 
• 593-51-1 methylamine hydrochloride 
• 537-46-2 Methamphetamin 
• 33817-09-3 (R)-2-methylamino-1-phenylpropane 
• 75-07-0 acetaldehyde 
• 1072-95-3 cyclohexylmethyl chloride 
• 74-89-5 methylamine 
• 7632-10-2 methamphetamin 
• 101-40-6 propylhexedrine 
• 1007-33-6 (+/-)-2-methylamino-1-cyclohexyl-propane; hydrochloride 
• 1334921-74-2 C₁₅H₂₃NO₂ 

Downstream Products

• 6556-29-2 (R)-2-methylamino-1-cyclohexyl-propane 
• 147282-89-1 N-(1-Cyclohexylprop-2-yl)-N-methylcarbamidsaeureethylester 
• 1591761-32-8 (S)-N-benzyl-1-cyclohexyl-N-methylpropan-2-amine hydrochloride 

Relevant academic research and scientific papers

An efficient, scalable process for benzphetamine hydrochloride

Commercial manufacturing of benzphetamine hydrochloride along with its impurity profiling is disclosed. Deoxygenation of pseudoephedrine is reported with ～100% retention by shielding the amine group as its tert-butyl carbamate, which is very straightforward to eliminate at the end. Four unknown process-related impurities are isolated from the samples of final API and characterized on the basis of their NMR and mass spectral analysis. Structures of the isolated impurities are confirmed by independent syntheses and coinjecting with the isolated one.

PROCESS FOR PREPARING BENZYLATED AMINES

This present invention relates to a process for preparing benzylated amines by the reaction of an amine selected from methamphetamine and propylhexedrine with benzyl halide. Numerous improvements are obtained by employing the amine in molar excess with respect to benzyl halide, preferably in a molar ratio of 2 to 1. The excess amine is employed to selectively neutralize by-product acid as the amine salt. The amine salt is then separated from the reaction mixture and basified to reclaim starting amine for recycle to the process.

Synthesis and structure-activity relationships of trisubstituted phenyl urea derivatives as neuropeptide Y5 receptor antagonists

1-((1R,2R)-2-Hydroxy-1-methyl-2-phenylethyl)-1-methyl-3-(4-phenoxyphenyl)urea (1) was identified as a hit from the screening of the neuropeptide Y5 (NPY5) receptor. This lead was optimized for in vitro potency by changing the stereochemistry, the phenylethyl segment, the urea portion, and the 4-phenoxyphenyl group on the molecule. Over 40 analogues of 1 were prepared to study the structure-activity relationship for this series. The most potent compounds in this class have IC50S less than 0.1 nM at the NPY5 receptor (e.g., 40f, 44a, and 47). To determine the functional activity for this series of compounds, selected analogues were tested in a cellular assay measuring forskolin-induced cyclic AMP accumulation in 293 cells transfected with the human NPY5 receptor. All urea analogues tested in the functional assay acted as antagonists (e.g., 1, 32, 40a, and 44e).

Hair analysis for drugs of abuse XXI. Effect of para-substituents on benzene ring of methamphetamine on drug incorporation into rat hair

In order to study the effect of para-substituents on the benzene ring of methamphetamine on drug incorporation into hair from blood, the plasma AUCs and hair concentrations of 7 methamphetamines [methamphetamine (MA), p- hydroxymethamphetamine (OHMA), p-bromomethamphetamine (BMA), p- aminomethamphetamine (AMA), p-nitromethamphetamine (NMA), p- methoxymethamphetamine (MOMA) and 3,4-methylenedioxymethamphetamine (MDMA)] plus propylhexedrine (PHX) in DA rats was determined after intraperitoneal injection at 5 mg/kg, with single dose for the plasma AUC and 10 doses for the hair concentration. Drug incorporation rates into hair (ICRs) were calculated by dividing each hair concentration by each plasma AUC. Comparing the highest value (NMA) to the lowest one (OHMA), the ICR of NMA was 31.7 times larger than that of OHMA. Using the ICR of MA which has no substitute on the benzene ring as a base point, nitro, bromo, methylenedioxy, methoxy and amino groups raised the drug incorporation into rat hair in this order. On the other hand, hydroxy substitution showed a negative effect on the ICR. In comparison between the ICRs of MA and PHX, it was found that the benzene ring shows higher affinity to melanin and less lipophilicity than the cyclohexyl ring. Our results showed that there is a relatively strong effect of the functional groups on drug incorporation into hair. The combination of melanin affinity and lipophilicity are clearly correlated with their ICR.