Organic Chemicals
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
Aromatic and heterocyclic amines are chemicals composed of single- and multiple-ring systems with an exocytic amino group. They do not occur in nature except for complex heterocyclines that are generated during pyrolysis. They are synthetics used in dye and drug manufacturing and as antioxidants.383 The typical monoarylamines and polyarylamines with carcinogenic potential include aniline and o-toluidine (sarcoma), o-anisidine and p-cresidine (bladder cancer), and phenacetin384 (Table 5.48). At high doses, anilines are carcinogenic, and through its metabolite phenylhydroxylamine, aniline is a powerful hematopoietic poison producing methemoglobinemia. o-Toluidine and 2,6-dimethylaniline are released from the local anesthetics prilocaine and lidocaine.385 High-level chronic abuse, but not ordinary intermittent drug use, of phenacetin has led to human bladder cancer.386 These aforementioned aromatic amines have been observed to trigger chemical sensitivity.
Toxicokinetics
Frank A. Barile in Barile’s Clinical Toxicology, 2019
The associated and dissociated structures of a base and an acid are illustrated in Figure 10.3 with aniline and benzoic acid, which possess strong basic and acidic characteristics, respectively. The structure of benzoic acid shows the carboxyl anion after dissociation. Since its pKa = 4, the Ka = 1 × 10−4, resulting in a higher dissociation constant and strong acidic properties. Similarly, aniline is a highly protonated species, with a pKb of 10 and corresponding Kb of 1 × 10−10 (pKa + pKb = 14; thus, although it is a base, the pKa of aniline can also be expressed as 4). The low dissociation constant of the base indicates that the H+ ions are closely held to the nitrogen and contribute to its strongly basic nature. Structures of aniline and benzoic acid.
Spectroscopy and Fluorimetry
Joseph Chamberlain in The Analysis of Drugs in Biological Fluids, 2018
The pH of samples used for measurement can dramatically affect the absorption spectrum, and this property should also be utilized in the development of a spectro-photometric method. The classic examples of this phenomenon are phenol and aniline. Phenol in its un-ionized form absorbs at 270 nm with a molar absorptivity of 1450. In alkaline solution, however, the phenate ion absorbs at 287 nm with an ɛ value of 2600. This increased absorbance is due to the presence of additional unshared electrons available for conjugation with the phenyl ring. Aniline, on the other hand, already has a pair of unshared electrons available for conjugation in the nonprotonated form; the absorption maximum of aniline in neutral or alkaline solution is at 280 nm with an ɛ value of 1430. The addition of acid results in protonation of the unpaired electrons, conjugation is decreased, and the absorption maximum shifts to 254 nm with an ɛ value of 160.
Pyrrolo[3,2-c]pyridine derivatives with potential inhibitory effect against FMS kinase: in vitro biological studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Mohammed I. El-Gamal, Chang-Hyun Oh
The 4-benzamidopyrrolo[3,2-c]pyridine derivatives 1a–k were synthesised as per the pathway illustrated in Scheme 1. Pyrrolo[2,3-b]pyridine (2) was treated with m-chloroperoxybenzoic acid to produce the m-chlorobenzoate salt 3. Heating compound 3 with phosphorus oxychloride yielded 4-chloropyrrolo[2,3-b]pyridine (4)22. Fusion of compound 4 with the appropriate nitroaniline yielded 1-aryl-4-aminopyrrolo[3,2-c]pyridine HCl salts (5a,b) after ring rearrangement23. The amines 5a,b were treated with benzoyl chloride in the presence of diisopropylamine to produce the corresponding benzamido analogues 6a,b. The nitro group of compounds 6a,b was reduced using hydrogen gas and Pd/C to yield the corresponding aniline derivatives 7a,b. In order to get the diarylurea products 1a–e, compounds 7a,b were reacted with appropriate aryl isocyanate at room temperature. On the other hand, heating the amines 7a,b with the appropriate benzoic acid derivative in the presence of EDCI, HOBt, and triethylamine led to condensation reaction and formation of the bisamide products 1f–k18–20.
Research progress of natural products and their derivatives against Alzheimer’s disease
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Jin-Ying Liu, Hong-Yan Guo, Zhe-Shan Quan, Qing-Kun Shen, Hong Cui, Xiaoting Li
Fonseca et al. modified the structure of coumarin and chromone, and evaluated their MAO-A and MAO-B inhibitory activities. The results showed that there was no significant difference between the two natural product derivatives in their activities. They had inhibitory effect on MAO-B and no significant activity on MAO-A. The MAO-B inhibitory activity of coumarin derivative 9 (IC50=5.07 nM), chromone derivative 10 (IC50=4.2 nM) and compound 11 (IC50=3.94 nM) is strong. The introduction of aniline has a good effect. The introduction of chlorine substituents at the same time can enhance the MAO-B inhibitory activity. The results of pharmacokinetics showed that compounds 9 and 10 had good binding power and selectivity through non-competitive inhibition23 (Figure 2, Table 1).
Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yuan Gao, Nian-Dong Mao, Hao Che, Li Xu, Renren Bai, Li-Wei Wang, Xiang-Yang Ye, Tian Xie
As mentioned above, compound 11h has better activity than 11b, and could serve as a new starting point for further optimisation. Since the aniline group is a known functional group for carcinogenicity, we decided to incorporate a nitrogen atom on the phenyl ring to mitigate such liability. Analog 11i was designed and synthesised for head-to-head comparison in biological testing. Notably, 11i exhibited more than 6-fold potency enhancement compared to 11h in anti-proliferative activities against A549 cells. To determine which portion of 11i contributed more to the activity, we designed two analogs 11j and 15. The absence of NH2 on pyridyl ring (i.e. 11j) tenuate the activity significantly (17.56 µM vs 1.67 µM to H1975 cell lines, 2.5 µM vs <1 µM to A549 cell lines, 5.71 vs 1.37 µM to H460 cell lines) compared to 11i, while the replacement of N-hydroxyl group with N-cyclopropyl group (i.e. 15) significantly reduce the anticancer activities in both H1975 (IC50 > 30 µM) and H460 cells lines (IC50 > 30 µM). These results pointed to a conclusion that both N-hydroxyl carboximate moiety and NH2 group on pyridyl ring were very important contributors for good biological activities of 11i.
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