Antihistamines, Decongestants, and Expectorants during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Brompheniramine, chlorpheniramine, dexchlorpheniramine, and triprolidine are propylamine derivatives. Brompheniramine was weakly associated with birth defects in 65 offspring exposed during the first trimester, but the association is not likely causative (Heinonen et al., 1977). In a larger study of 270 infants born following first-trimester exposure to brompheniramine, birth defects were not increased in frequency among 270 infants whose mothers took brompheniramine during embryogenesis (Aselton et al., 1985; Jick et al., 1981). Analysis of pheniramine (either brompheniramine or chlorpheniramine) in the National Birth Defects Prevention Study found no causal relationship between birth defects and first trimester exposure to these pheniramines (Gilboa et al., 2009). Meta-analysis of available data on brompheniramine indicate it is not a human teratogen (Seto et al., 1993) and this finding is supported by a recent review (Gilbert et al., 2005) that included more information than the meta-analysis (Table 11.3).
Substrates of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
Chlorpheniramine, a propylamine H1 receptor antagonist available as an over-the-counter drug, is indicated for use in the common cold and for symptomatic treatment of allergies. Chlorpheniramine has a chiral carbon and is usually given as a racemic mixture, and it demonstrates stereoselectivity in its disposition (Yasuda et al. 2002) and pharmacological response (Tran et al. 1978). The S-enantiomer is approximately 100 times more potent than the R-enantiomer with regard to the antihistamine activity (Tran et al. 1978). The metabolism of chlorpheniramine has been extensively studies in animals (Cashman et al. 1992a; Kammerer and Lampe 1987; Nomura et al. 1997; Peets et al. 1972), and it has been found that chlorpheniramine undergoes extensive N-demethylation. Rat CYP2B1 and 2C11 are involved in its N-demethylation (Nomura et al. 1997). Chlorpheniramine can also be converted to its N-oxide by FMO from hog liver (Cashman et al. 1992a). In humans, chlorpheniramine is N-demethylated by CYP2D6 (Figure 3.74). For S-chlorpheniramine, administration of quinidine, an inhibitor of CYP2D6, results in an increase in Cmax, a reduction in oral clearance, and a prolongation of elimination half-life. Administration of quinidine decreased the oral clearance of R-chlorpheniramine. Stereoselective elimination of chlorpheniramine occurs in humans, with the most pharmacologically active S-enantiomer cleared more slowly than the R-enantiomer. In addition, a difference in receptor occupancy is observed between individuals who are CYP2D6 PMs or EMs (Yasuda et al. 1995).
Synthetic Nanoparticles for Anticancer Drugs
Harishkumar Madhyastha, Durgesh Nandini Chauhan in Nanopharmaceuticals in Regenerative Medicine, 2022
Nanoparticles (NPs) are having a considerable impact on modern medical applications. They are used for drug delivery systems and targeted therapy. Nanoparticles are composed of metal, nonmetal atoms, or a mixture of both. CSA-13 is an example of a synthetic NP, which is composed of an iron oxide anion, an aminosilane group, and the antibacterial peptide LL-37. Propylamine groups, which are placed in the core of the magnetic NPs structure, were synthesized using the modified Stöber method (Geetha et al. 2013).
Discovery of new 1H-pyrazolo[3,4-d]pyrimidine derivatives as anticancer agents targeting EGFRWT and EGFRT790M
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Ahmed A. Gaber, Mohamed Sobhy, Abdallah Turky, Hanan Gaber Abdulwahab, Ahmed A. Al-Karmalawy, Mostafa. A. Elhendawy, Mohamed. M. Radwan, Eslam B. Elkaeed, Ibrahim M. Ibrahim, Heba S. A. Elzahabi, Ibrahim H. Eissa
The designed compounds were synthesised as outlined in Schemes 1–3. Ethoxymethylene malononitrile 141 was allowed to react with phenylhydrazine to produce 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile 244. Compound 2 underwent partial hydrolysis using alcoholic NaOH to produce carboxamide derivative 345. Fusion of compound 3 with urea afforded 1-phenyl-1,7-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4,6(5H)-dion 4. Chlorination of compound 4 using phosphorus oxychloride and phosphorus pentachloride produced 4,6-dichloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine 546. Stirring of compound 5 with aniline at room temperature afforded 4-chloro-N,1-diphenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-amine 647. The obtained compound 6 was heated with commercially available different amines, namely ethylamine, propylamine, aniline, and cyclohexylamine in the presence of triethylamine afforded the target compounds 7a,b, 8, and 9, respectively. The IR spectra of 7a,b, and 9 demonstrated stretching bands at a range of 2950 − 2980 cm−1 corresponding to CH aliphatic groups. The 1H NMR spectra were characterised with abroad singlet at approximately 7–8 ppm due to the additional NH group.
Enaminone-based carboxylic acids as novel non-classical carbonic anhydrases inhibitors: design, synthesis and in vitro biological assessment
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mahmoud F. Abo-Ashour, Hadia Almahli, Alessandro Bonardi, Amira Khalil, Tarfah Al-Warhi, Sara T. Al-Rashood, Hatem A. Abdel-Aziz, Alessio Nocentini, Claudiu T. Supuran, Wagdy M. Eldehna
Moreover, the stopped-flow assay outputs showed that the physiologically relevant hCA II isoform was affected by herein reported carboxylic acids bearing enaminones 5a–q and carboxylic acids 7a–b. Both the ortho and meta carboxylic acids bearing enaminones (5a–e and 5f–k) moderately inhibited hCA II isoform with inhibition constants spanning in the ranges 24.3–49.0 µM and 68.2–92.3 µM, respectively, whereas the para carboxylic acids bearing enaminones 5l–q effectively inhibited this isoform (KI range: 7.4–15.3 µM). In addition, carboxylic acids 7a–b with a saturated 3-oxo-propylamine linker displayed KI values equal to 64.3 µM and 16.7 µM, respectively. In particular, the best inhibitory activity in the CO2 hydrase assay was demonstrated by the para carboxylic acids bearing enaminones 5l, 5m and 5q that showed KI values in the single-digit micromolar range equal to 9.8 µM, 8.7 µM and 7.4 µM, respectively. Also, carboxylic acids 5n, 5o, 5p and 7b exhibited good activity against hCA II isoform with KI = 13.5 µM, 15.3 µM, 12.6 µM and 16.7 µM, respectively.
Design, synthesis, and anticonvulsant effects evaluation of nonimidazole histamine H3 receptor antagonists/inverse agonists containing triazole moiety
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Mingxia Song, Rui Yan, Yanhui Zhang, Dongfu Guo, Naiming Zhou, XianQing Deng
Simple structure–activity relationships (SARs) could be obtained from Table 1. In the series of 3a-3j, the different tertiary amines significantly influenced the H3R antagonistic activities. The N-ethyl derivative 3a showed an IC50 of 2.9 µM, while the activity declined sharply for the N-propyl derivative 3b. Interestingly, compounds containing piperazine or morpholine (3d-3g) exhibited weaker activities than those with piperidine or pyrrolidine (3c and 3h). This probably attributed to the increase of the molecular polarity. The introduction of phenyl or amide group on the piperidine ring of compound 3h, gave the compounds 3i and 3j, which also decreased the H3R antagonistic activities when compared to compound 3h. Based on the facts above, it could be concluded that the N,N-diethyl group, pyrrolidine and piperidine were more of benefit to the H3R antagonistic activities of the 3-(4-(4H-1,2,4-triazol-4-yl)phenoxy)-propylamine skeleton, and piperidine derivative (3h) was the best one with the IC50 of 0.127 µM.
Related Knowledge Centers
- Acid Dissociation Constant
- Amine
- 1-Propanol
- Ammonium Chloride
- Iron(Iii) Chloride