1690-22-8Relevant academic research and scientific papers
Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine
Bédard, Anne-Catherine,Longstreet, Ashley R.,Britton, Joshua,Wang, Yuran,Moriguchi, Hideki,Hicklin, Robert W.,Green, William H.,Jamison, Timothy F.
, p. 6233 - 6241 (2017)
Minimizing the waste stream associated with the synthesis of active pharmaceutical ingredients (APIs) and commodity chemicals is of high interest within the chemical industry from an economic and environmental perspective. In exploring solutions to this area, we herein report a highly optimized and environmentally conscious continuous-flow synthesis of two APIs identified as essential medicines by the World Health Organization, namely diazepam and atropine. Notably, these approaches significantly reduced the E-factor of previously published routes through the combination of continuous-flow chemistry techniques, computational calculations and solvent minimization. The E-factor associated with the synthesis of atropine was reduced by 94-fold (about two orders of magnitude), from 2245 to 24, while the E-factor for the synthesis of diazepam was reduced by 4-fold, from 36 to 9.
Isotopically labelled tropane alkaloids. The synthesis of (RS)-[3′, 3′-2H2]- and (RS)-[1′-13C, 3′, 3′-2H2]- hyoscyamines for metabolism studies in plants
Patterson, Stephen,O'Hagan, David
, p. 191 - 198 (2002)
A synthetic route to isotopically labelled forms of the tropane alkaloid hyoscyamine, including (RS)-[3′, 3′,-2H2]- (2a) and (RS)-[1′-13C, 3′, 3′,-2H2]- (2b) hyoscyamines, involving the reaction betwe
An anti-choline medicine preparation method of atropine sulfate
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Paragraph 0035; 0036, (2017/03/08)
The invention provides a synchronizing method of atropine sulphate. The method is characterized in that hydrolyzing methyl phenoxyacetate (II) is hydrolyzed to obtain a compound (III); the compound (III) and thionyl chloride are subjected to acylation reaction to obtain a compound (IV); the compound (IV) and 8-methyl-8-azabicyclo[3.2.1]oct-3-alchol are subjected to condensation reaction to obtain a compound (V); the compound (V) and paraformaldehyde are used for producing atropine (VI) under an alkaline condition; the atropine (VI) is salified under an acidic condition to obtain the atropine sulphate (I). The preparation method is simple in technology, high in yield, high in purity, low in monomer impurity and easy for industrial production.
Synthesis, antimuscarinic activity and quantitative structure-activity relationship (QSAR) of tropinyl and piperidinyl esters
Xu, Rong,Sim, Meng-Kwoon,Go, Mei-Lin
, p. 231 - 241 (2007/10/03)
A series of tropinyl and piperidinyl esters was synthesized and evaluated for inhibitory activities on the endothelial muscarinic receptors of rat (M3) and rabbit (M2) aorta. Some of the esters (cyclohexylphenylglycolates and cyclohexylphenylpropionates) were found to be better antimuscarinic compounds than standard M2 and M3 inhibitors such as AFDX116 and 4-diphenylacetoxy-N-methylpiperidine (DAMP), with pKEC50 values in the range of 8-9. A few esters were found to be more selective M3 than M2 inhibitors, but these tended to have low activities. The hydrophobic, electronic and steric characteristics of these esters were correlated with antimuscarinic activity by using appropriate parameters representing hydrophobicity (HPLC capacity factor, log k(w), size (molecular volume) and electronic character (Taft's polar substituent constant δ and 13C chemical shift difference Δδ). Finally, 92% of the M2-inhibitory activities of the esters could be accounted for by the size and electronic character σ* of the side chain. In contrast, the M3-inhibitory activities of these esters were mainly attributed to the electronic nature (σ*, Δδ) of the side chain, with good activity being associated with electron-withdrawing groups. Visualization of the comparative molecular field analysis (CoMFA) steric and electrostatic fields provided further confirmation of the structure-activity relationship (SAR) derived from traditional quantitative structure-activity relationship (QSAR) approaches.
Presynaptic cholinergic modulators as potent cognition enhancers and analgesic drugs. 1. Tropic and 2-phenylpropionic acid esters
Gualtieri,Conti,Dei,Giovannoni,Nannucci,Romanelli,Scapecchi,Teodori,Fanfani,Ghelardini,Giotti,Bartolini
, p. 1704 - 1711 (2007/10/02)
Previous studies have shown that (R)-(+)-hyoscyamine has analgesic activity as a consequence of increased ACh release following antagonism of central muscarinic autoreceptors. Since the enhancement of central cholinergic transmission could be beneficial for cognitive disorders, we manipulated (R)-(+)-hyoscyamine, synthesizing several derivatives of tropic and 2-phenylpropionic acids, with the aim of obtaining drugs which are able to increase ACh release and consequently to show analgesic and nootropic activities. The results showed that several new compounds are indeed potent analgesics (with an analgesic efficacy comparable to that of morphine) and that the most potent one ((±)-19, PG9) also has remarkable cognition- enhancing properties. Our study confirmed that the mechanism of action involves ACh release even if it is still unclear whether only muscarinic autoreceptors or, also, heteroreceptors are involved.
