4740-24-3Relevant articles and documents
N-Trifluoromethyl Amines and Azoles: An Underexplored Functional Group in the Medicinal Chemist's Toolbox
Schiesser, Stefan,Chepliaka, Hanna,Kollback, Johanna,Quennesson, Thibaut,Czechtizky, Werngard,Cox, Rhona J.
, p. 13076 - 13089 (2020/11/13)
Introducing trifluoromethyl groups is a common strategy to improve the properties of biologically active compounds. However, N-Trifluoromethyl moieties on amines and azoles are very rarely used. To evaluate their suitability in drug design, we synthesized a series of N-Trifluoromethyl amines and azoles, determined their stability in aqueous media, and investigated their properties. We show that N-Trifluoromethyl amines are prone to hydrolysis, whereas N-Trifluoromethyl azoles have excellent aqueous stability. Compared to their N-methyl analogues, N-Trifluoromethyl azoles have a higher lipophilicity and can show increased metabolic stability and Caco-2 permeability. Furthermore, N-Trifluoromethyl azoles can serve as bioisosteres of N-iso-propyl and N-Tert-butyl azoles. Consequently, we suggest that N-Trifluoromethyl azoles are valuable substructures to be considered in medicinal chemistry.
Method for preparing tetracaine hydrochloride
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Paragraph 0041, (2019/01/21)
The invention discloses a method for preparing tetracaine hydrochloride. The method comprises the following steps: (1) preparing 4-n-butyl aminobenzoic acid, namely adding a solvent, 4-halogen-benzoicacid, n-butylamine and copper catalyst into a high pressure reactor to obtain the 4-n-butyl aminobenzoic acid; (2) preparing tetracaine, namely adding the 4-n-butyl aminobenzoic acid prepared in thestep (1), N,N-dimethylethanolamine, concentrated sulfuric acid and a solvent into a reaction bottle, heating, refluxing and diverting to obtain the tetracaine; and (3) preparing tetracaine hydrochloride, namely reacting the tetracaine prepared in the step (2) with concentrated hydrochloric acid in a solvent at a certain temperature to obtain the tetracaine hydrochloride. The method has the advantages that 1, the copper catalyst has smaller toxicity, is low in price and easily available while the copper catalyst is much safer, and the cost for raw materials and operation can be greatly reduced;2, the raw materials are easily available, the reaction has few steps, the intermediate reacting process can be easily controlled, few byproduct is generated, and large-scale production is easy to implement; and 3, the product has high purity and high total yield.
Cyclic nucleotide-gated channel block by hydrolysis-resistant tetracaine derivatives
Andrade, Adriana L.,Melich, Kenneth,Whatley, G. Gregory,Kirk, Sarah R.,Karpen, Jeffrey W.
experimental part, p. 4904 - 4912 (2011/09/19)
To meet a pressing need for better cyclic nucleotide-gated (CNG) channel antagonists, we have increased the biological stability of tetracaine-based blockers by synthesizing amide and thioamide linkage substitutions of tetracaine (1) and a higher affinity
