HIV Integrase Inhibitors
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
It was soon realized that polyhydroxylated aromatic compounds (catechol) are not selective inhibitors against IN 3′-processing or strand transfer reactions, show significant cytotoxicity, have low oral bioavailability, and are not metabolically stable. It could be because the cellular oxidation of catechol to semiquinone or orthoquinone results in reactive intermediate capable of interacting with other cellular targets. Attempts to improve the biological activity of catechol derivatives by substitution or removal of the hydroxyl group resulted in the complete loss of IN inhibitory activity. The National Cancer Institute (NCI) 3D database of pharmacophore-based searches and computational molecular modeling approaches identified several active structures devoid of catechol moiety (Neamati 2011). Among them, coumarins, hydrazides, quinones, sulfones, sulfonamides, diketo acids (DKAs), naphthyridines, and pyrimidinones were explored extensively. Raltegravir, the first FDA-approved IN inhibitor drug, was the result of research on pyrimidinone carboxamides, whereas elvitegravir, the second FDA-approved IN inhibitor drug, resulted from research on quinolinoyl carboxylic acids. Several other diverse compounds uniquely different from many examples mentioned earlier have been reported to inhibit IN. Some of them, such as thiazolothiazepines, chalcones, dihydropyridine carboxylic acids, benzoxazoles, tetrazoles, and benzene tricarboxamides, were extensively optimized in search of potent and selective IN inhibitors. Many QSAR studies on these inhibitors were reported and are discussed in this section.
Identification of New Diflunisal Derivatives as Potent In Vitro Transthyretin Fibril Inhibitors
Gilles Grateau, Robert A. Kyle, Martha Skinner in Amyloid and Amyloidosis, 2004
It is known that certain classes of compounds such as salicylates, steroids, antibiotics (penicillin, triiodophenol), flavonoids, inotropic agents (milrinone) and PCBs bind with high affinity to transthyretin (TTR). More recently, some members of a number of these and other families of already known therapeutic compounds such as flavones, tetrahydroquinolines, dihydropyridines, benzodiazepines, NSAIDs, phenoxazines, stilbenes, benzoxazoles and natural products (resveratrol) have also been identified and characterized as in vitro TTR fibril inhibitors by limited screening studies (2).
Classifications
Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani in Pharmacology in 7 Days for Medical Students, 2018
Centrally-acting muscle relaxantsBenzodiazepinesClorazepateDiazepamKetazolamMedazepamBenzoxazole derivativesBenzimidazoleChlorzoxazoneZoxazolamineGABA analogueBaclofenMiscellaneous compoundsCyclobenzaprineChlormezanoneChlorphensinMethocarbamolOrphenadrine HClOrphendrine citratePropanediol derivativesCarisoprodolMephenesinMeprobamateStyramate
Therapeutic potential of oxazole scaffold: a patent review (2006–2017)
Published in Expert Opinion on Therapeutic Patents, 2018
Ramandeep Kaur, Kezia Palta, Manoj Kumar, Meha Bhargava, Lalita Dahiya
Oxazole (1) is a well-known important heterocyclic motif characterized as 1,3-azole possessing oxygen and nitrogen atoms in 1,3 relationship of five membered ring. This was first reported by Hantzsch in 1887 and synthesized in 1947. Annuloline was the first demonstration of oxazole ring in nature. Benzo derivatives of oxazole are called as benzoxazole (2). Partially reduced oxazoles are called oxazolines and depending upon the position of the double bond are named as 2-oxazoline (3), 3-oxazoline (4), and 4-oxazoline (5), whereas, the fully saturated analog is called as oxazolidine (6). Oxazole is weakly basic liquid, miscible with water and organic solvents and has dipole moment of 1.5 D. Although the sextet of π-electrons is present in oxazole ring, its properties have demonstrated incomplete delocalization of π-electrons that attributes to its little aromaticity and greater dienic character. This lower aromaticity is not to be equated with instability [5–8].
Design, synthesis, and biological evaluation of benzoheterocyclic sulfoxide derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Shen Mao, Qiaoqiang Li, Zhikun Yang, Yasheng Li, Xinyi Ye, Hong Wang
Next, to further explore the effect of Rʺ as substitution on the anti-biofilm activity, compounds 7, 8, and 9 were synthesised. Antibiofilm activity was enhanced when chloro-substitution on aromatic ring involved. When 5- or 6-position of benzoxazole ring was substituted by chloro, 6b and 7b showed good inhibitory activities (Table 2). Especially, the inhibition rate of 7b was 43.64 ± 2.49%, which meant that there was no difference between the chloro-substitutions at the 5- and 6-position on benzoxazole ring. However, when we changed the chloro-substitution on 5-position of benzoxazole ring to methyl or methoxy group, the inhibition rate of 8b and 9b were 19.93 ± 0.57% and 29.44 ± 0.39%. 8 and 9 with various substitutions had no particularly excellent inhibition effects except for 9b and 9f. A comparison with the serials data of 6 indicated that both the benzoxazole ring and the chloro-substitution were the key active functional group. Preliminary structure-activity relationships indicated that the benzoxazole heterocyclic ring was critical for optimal activity. In addition, the para-position on aromatic ring of benzyl group was an excellent choice for inhibitors design.
New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Hazem Elkady, Alaa Elwan, Hesham A. El-Mahdy, Ahmed S. Doghish, Ahmed Ismail, Mohammed S. Taghour, Eslam B. Elkaeed, Ibrahim H. Eissa, Mohammed A. Dahab, Hazem A. Mahdy, Mohamed M. Khalifa
The target benzoxazole derivatives 14a–o were synthesised following the general methodologies outlined in Schemes 1–3. The starting compounds, 2-mercapto-benzoxazoles 8a–c were synthesised by refluxing the appropriate 2-aminophenol derivatives 7a–c, carbon disulphide, and potassium hydroxide in methanol following the reported procedure33. Then, compounds 8a–c were treated with alcoholic KOH to afford the corresponding potassium salts, 9a–c (Scheme 1). On the other hand, 4-aminobenzoic acid 10 was reacted with chloroacetyl chloride in DMF to afford the chloroacetamide intermediate 11. Acylation of compound 11 was performed using thionyl chloride to yield 4–(2-chloroacetamido)benzoyl chloride 12 as described in the reported procedures14,34. Treating of 12 with commercially available amines namely, 2-methoxyaniline, 2,6-dimethoxyaniline, 2,6-dimethylaniline, 2,4-dichloroaniline, and 4-hydroxyaniline, in acetonitrile containing triethylamine (TEA), afforded the target key intermediates 13a–e (Scheme 2).
Related Knowledge Centers
- Aromaticity
- Atom
- Benzene
- Organic Compound
- Oxygen
- Pyridine
- Oxazole
- Flunoxaprofen
- Tafamidis
- Optical Brightener