| 1. |
- Shahid, Shereena, et al.
(författare)
-
A Review on the Scope of TFDO-Mediated Oxidation in Organic Synthesis-Reactivity and Selectivity
- 2018
-
Ingår i: Current Organic Synthesis. - : Bentham Science Publishers Ltd.. - 1570-1794 .- 1875-6271. ; 15:8, s. 1091-1108
-
Forskningsöversikt (refereegranskat)abstract
- Dioxiranes are three-membered strained ring peroxides that are typical archetype examples of electrophilic entities. A dioxirane-based oxidant named 3-methyl(trifluoromethyl)dioxirane (TFDO) is a fluorinated analogue of the extremely valuable oxidant dimethyldioxirane (DMDO). Owing to the strained three-membered ring and presence of electron-withdrawing trifluoromethyl group, TFDO is several times more reactive than DMDO and acts as a significant chemical reagent. Moreover, TFDO exhibits high regio-, chemo- and stereo-selectivity even under unusual reaction conditions, i.e. at pH values close to neutrality and at sub-ambient temperatures. The TFDO transfers an oxygen atom to "unactivated" carbon-hydrogen bonds of alkanes as well as to the double bonds of alkenes and also helps in oxidation of compounds containing heteroatoms having a lone pair of electrons, such as sulfides and amines. TFDO-mediated oxidation is considered to be one of the main procedures in the 21st century for the synthesis of oxygen-containing organic molecules. This review throws light on the applications of TFDO in organic syntheses to provide an insight into the future research and gives a comprehensive summary of the selective functionalization of activated and non-activated organic compounds.
|
|
| 2. |
- Channar, Pervaiz Ali, et al.
(författare)
-
Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid
- 2018
-
Ingår i: Bioorganic chemistry (Print). - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0045-2068. ; 79, s. 293-300
-
Tidskriftsartikel (refereegranskat)abstract
- Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC50 = 1.568 +/- 0.01 mu M) showed relatively better potential compared to reference kojic acid (IC50 = 16.051 +/- 1.27 mu M). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 angstrom which might be responsible for higher activity compared to Kojic acid.
|
|
| 3. |
- Ujan, Rabail, et al.
(författare)
-
Drug-1,3,4-Thiadiazole Conjugates as Novel Mixed-Type Inhibitors of Acetylcholinesterase : Synthesis, Molecular Docking, Pharmacokinetics, and ADMET Evaluation
- 2019
-
Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:5
-
Tidskriftsartikel (refereegranskat)abstract
- A small library of new drug-1,3,4-thiazidazole hybrid compounds (3a-3i) was synthesized, characterized, and assessed for their acetyl cholinesterase enzyme (AChE) inhibitory and free radical scavenging activities. The newly synthesized derivatives showed promising activities against AChE, especially compound 3b (IC50 18.1 +/- 0.9 nM), which was the most promising molecule in the series, and was substantially more active than the reference drug (neostigmine methyl sulfate; IC50 2186.5 +/- 98.0 nM). Kinetic studies were performed to elucidate the mode of inhibition of the enzyme, and the compounds showed mixed-type mechanisms for inhibiting AChE. The Ki of 3b (0.0031 mu M) indicates that it can be very effective, even at low concentrations. Compounds 3a-3i all complied with Lipinski's Rule of Five, and showed high drug-likeness scores. The pharmacokinetic parameters revealed notable lead-like properties with insignificant liver and skin-penetrating effects. The structure-activity relationship (SAR) analysis indicated pi-pi interactions with key amino acid residues related to Tyr124, Trp286, and Tyr341.
|
|
| 4. |
- Larik, Fayaz Ali, et al.
(författare)
-
Synthetic approaches towards the multi target drug spironolactone and its potent analogues/derivatives
- 2017
-
Ingår i: Steroids. - : Elsevier BV. - 0039-128X .- 1878-5867. ; 118, s. 76-92
-
Forskningsöversikt (refereegranskat)abstract
- Spironolactone is a well-known multi-target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment of edema, cirrhosis of the liver, malignant, pediatric, nephrosis and primary hyperaldosteronism. Spironolactone in association with thiazide diuretics treats hypertension and in association with furosemide treats bronchopulmonary dyspepsia. The therapeutic mechanism of action of spironolactone involves binding to intracellular mineralocorticoids receptors (MRs) in kidney epithelial cells, thereby inhibiting the binding of aldosterone. Since its first synthesis in 1957 there are several synthetic approaches have been reported throughout the years, Synthetic community has devoted efforts to improve the synthesis of spironolactone and to synthesize its analogues and derivatives. This review aims to provide comprehensive insight for the synthetic endeavors devoted towards the synthesis of a versatile drug spironolactone and its analogues/derivatives.
|
|
| 5. |
- Larik, Fayaz Ali, et al.
(författare)
-
The role of Lawesson's reagent in the total synthesis of macrocyclic natural products
- 2017
-
Ingår i: Phosphorus Sulfur and Silicon and the Related Elements. - : TAYLOR & FRANCIS LTD. - 1042-6507 .- 1563-5325. ; 192:5, s. 490-502
-
Forskningsöversikt (refereegranskat)abstract
- This review, including 111 references, describes the applications of Lawesson's reagent (LR) [2,4-bis(p-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-dithione] for the total synthesis of macrocyclic natural products. LR is a versatile reagent and shows excellent regioselectivity, chemoselectivity, and offers the products in high yield. The thionation of carbonyl moieties present in macrocyclic natural products, and cyclization to construct key heterocyclic fragments is described. Moreover, this review highlights the medicinal significance of the natural products. [GRAPHICS] .
|
|
| 6. |
- Saeed, Aamer, et al.
(författare)
-
Advances in transition-metal-catalyzed synthesis of 3-substituted isocoumarins
- 2017
-
Ingår i: Journal of Organometallic Chemistry. - : ELSEVIER SCIENCE SA. - 0022-328X .- 1872-8561. ; 834, s. 88-103
-
Forskningsöversikt (refereegranskat)abstract
- 3-Substituted isocoumarins are the most abundant class of naturally isocoumarins, found in several biologically active scaffolds and are precursors towards complex natural products. Considerable attempts have been devoted to the synthesis of these isocoumarins both by metal free or transition-metalcatalyzed reactions. Among the metal catalyzed reactions, the use of palladium, copper, gold, iron, nickel, rhodium, ruthenium, zinc, chromium, iridium, silver or thallium salts/complexes for the construction of 3-substituted isocoumarin ring is noteworthy due to being economical and good functional group tolerance. The current review focusses the recent reports on the Pd-, Cu-, Ag-, Fe-, Ni-, Rh-, Ru-, Zn, Cr-, Ir-, Ag- and Ti -catalyzed synthesis of isocoumarins.
|
|
| 7. |
- Saeed, Aamer, et al.
(författare)
-
Developments in the synthesis of the antiplatelet and antithrombotic drug (S)-clopidogrel
- 2017
-
Ingår i: Chirality. - : Wiley. - 0899-0042 .- 1520-636X. ; 29:11, s. 684-707
-
Forskningsöversikt (refereegranskat)abstract
- S-(+)-Methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate, also known as (S)-clopidogrel, is marketed under the trade names Plavix and Iscover. It is a potent thienopyridine-class of antithrombotic and antiplatelet drug (antiaggregant). Among the two available stereoisomers of clopidogrel, for pharmaceutical activities only the S-enantiomer is applicable, as no antithrombotic activity is observed in the R-enantiomer and causes political upheavals and social turmoil in animal experiments. Worldwide sales of Plavix amounted to $6.4 billion yearly, which ranks second. Attributed to the increased demand of (S)-clopidogrel drug, it provoked the synthetic community to devise facile synthetic approaches. This review aims to summarize the synthetic methods of (S)-clopidogrel drug reported in the literature. The present review discusses the pros and cons of each synthetic methodology, which would be beneficial to the scientific community for further developments in the synthetic methodologies for (S)-clopidogrel. In addition, the compilation approach of literature-reported synthetic strategies of (S)-clopidogrel in one platform is advantageous, supportive, and crucial for the synthetic community to elect the best synthetic methodology of (S)-clopidogrel and to create new synthesis ideas.
|
|
| 8. |
- Saeed, Aamer, et al.
(författare)
-
Recent Progress in Pyridine Containing Heterocycles as High Performance Host Materials for Blue PHOLEDs
- 2018
-
Ingår i: Mini-Reviews in Organic Chemistry. - 1570-193X .- 1875-6298. ; 15:4, s. 261-273
-
Forskningsöversikt (refereegranskat)abstract
- Phosphorescent Organic Light-Emitting Diodes (PHOLEDs) have an advantage of stability for a lifetime in comparison with the conventional Organic Light-Emitting Diodes (OLEDs). Green and red OLEDs have already achieved success, but for the last decade, blue OLEDs have observed a surge in the attention towards them from academia as well as the industry. There are incessant efforts devoted towards the improvement of external quantum efficiency from 25-30%. The host materials (or host compounds), hole transporting and electron transporting are the preeminent factors for the enhancement of External Quantum Efficiency (EQE). This review aims at highlighting the role of pyridine as an efficient Electron Transporting Material (ETM) for blue PHOLEDs. Pyridine having electron withdrawing nature can serve as valuable host compounds for electron transport material in PHOLEDs of a blue color. The presence of nitrogen atom in pyridine facilitates in lowering HOMO/LUMO energy levels compared to benzene ring and this assists in adding phenyl rings at the periphery of pyridine ring.
|
|
| 9. |
- Saeed, Aamer, et al.
(författare)
-
Recent resurgence toward the oxidation of heteroatoms using dimethyldioxirane as an exquisite oxidant
- 2017
-
Ingår i: Synthetic Communications. - : TAYLOR & FRANCIS INC. - 0039-7911 .- 1532-2432. ; 47:9, s. 835-852
-
Forskningsöversikt (refereegranskat)abstract
- This review covers the literature from 2005 to till date. Oxidation chemistry is a dynamic field of organic synthesis as it keeps evolving with the passage of time. There is a recent surge in that area to switch over from inorganic oxidants to organic oxidants. The oxidation of heteroatom is an intriguing task for the synthetic chemists, as it requires mild oxidant with no harmful side products. Dimethyldioxirane serves as a super-effective oxidant as it shows high functional group tolerance and possess acetone as byproducts which is also eco-friendly. This review summarizes the heteroatom oxidation of sulfur, nitrogen, iodine, selenium, phosphorous, and platinum atoms using DMDO as an oxidant.
|
|
| 10. |
- Shahzad, Danish, et al.
(författare)
-
Novel C-2 Symmetric Molecules as -Glucosidase and -Amylase Inhibitors : Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics
- 2019
-
Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:8
-
Tidskriftsartikel (refereegranskat)abstract
- A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a-5h, have been synthesized, characterized by H-1-NMR and C-13-NMR, and evaluated for their in vitro -glucosidase and -amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both -glucosidase and -amylase. The IC50 of 5g against -glucosidase was 0.35917 +/- 0.0189 mu M (standard acarbose IC50 = 6.109 +/- 0.329 mu M), and the IC50 value of 5g against -amylase was 0.4379 +/- 0.0423 mu M (standard acarbose IC50 = 33.178 +/- 2.392 mu M). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of -glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 angstrom, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results
|
|
