Green synthesis,molecular docking and pharmacological evaluation of new triazolo-thiadiazepinylcoumarine derivatives as sedative-hypnotic scaffold

4-Amino-5-mercapto-4H-1,2,4-triazole derivative 1 was used as a key intermediate for the preparation of 1,2,4-triazolo[3,4-b][1,3,4]thiadiazepine derivatives 5a-d , 12a-g , and 16 via reactions with the appropriate chalcones 2a-d , α,β-unsaturated carbonitrile derivatives 9a-g and 13 , respectively. The identity of the synthesized compounds was elucidated via their spectral data and elemental analysis. Moreover, the sedative-hypnotic activity of the newly synthesized compounds were evaluated and showed excellent activities especially compounds 12b , 12f , and 16 . Also, their structure activity relationship (SAR) was clearly demonstrated and showed that the electron-donating groups enhance activities while electron-withdrawing groups decrease activities. The molecular docking of the most active derivative 16 against γ-amino butyric acid (GABA) receptor was performed by the MOE 2014 0901program. The acquired outcomes demonstrated that the most active compounds could be a helpful model for future structure, adjustment, and examination to build more active analogs.     

Thiophene aldehyde and its derivatives. II

Condensation of thiophene-2-aldehyde with p-aminobenzoic and barbituric acids gives 2-thenylidene -p-aminobenzoic acid and 2-thenyl-idenebarbituric acid. Similarly, 5-nitro-thiophene-2-aldehyde gives 5-nitro-2-thenylidene-p-aminobenzoic acid and 5-nitro-2-thenyl-idenebarbituric acid. Condensation of thiophene-2-aldehyde with nitroethane gives 1-(2-thienyl)-2-nitroprop-1-ene; and 1-nitro-2-(2-thienyl-5-nitro) ethene is synthesized by nitrating thienylnitroethylene.     

Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent antihypertensive agents with antiplatelet aggregation activity

A series of 1-aminoalkyl-pyrrolo[2,3-c]azepin-8-one derivatives was synthesized and evaluated as alpha 1 adrenergic and serotonin 2 (5-HT2) receptor antagonists, with the aim of finding a novel antihypertensive agent potently exhibiting both activities. Some compounds with a 4-[4-(4-fluorobenzoyl)piperidino]butyl group at the 1-position exhibited both activities, and varied significantly in terms of the substituents at the 4-position of the pyrroloazepine ring. Among the compounds obtained in this study, (E)-1-[4-[4-(4-fluorobenzoyl)piperidino]-butyl]-4-hydroxyimino-7- methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-one (15a, SUN9221) displayed potent alpha 1-adrenergic antagonistic activity (pA2 = 8.89 +/- 0.21) and 5-HT2 antagonistic activity (pA2 = 8.74 +/- 0.22) in isolated guinea pig arteries. This compound exhibited antihypertensive activity and a duration of action equivalent to orally administered prazosin or doxazosin, 3 mg/kg, in conscious spontaneously hypertensive rats, as well as potent antiplatelet aggregation activity.     

Synthesis,molecular modeling,and pharmacological evaluation of new 2-substituted benzoxazole derivatives as potent anti-inflammatory agents

Structural Chemistry - In the present work, 2-substituted benzoxazole derivatives were synthesized from 2-(benzo[d]oxazol-2-yl) aniline. All the synthesized compounds were purified and...     

Decoquinate derivatives: A new class of potent antischistosomal agents against Schistosoma japonicum

Decoquinate (1), an old and inexpensive coccidiostat, exhibited potent antimalarial activity, however, its antischistosomal activity against Schistosoma japonicum has not yet been evaluated. Based on decoquinate, a series of decoquinate derivatives was designed, synthesized, evaluated as a new class of antischistosomal agents against S. japonicum adult worms in vitro. Among them, compound 15 killed 100% of adult S. japonicum in 72 h at the concentration of 10 μmol/L in vitro, exhibited stronger wormkilling activity than PZQ in vitro and could serve as a promising lead compound to develop new antischistosomal agents.     

Synthesis and novel structure-activity relationships of potent sansalvamide A derivatives

Synthesis of twelve Sansalvamide A derivatives and their SAR against colon cancer (HT-29).     

Thiophene Scaffold as Prospective Antimicrobial Agent: A Review

Thiophene has emerged as a potent scaffold that has pulled the keen interest of the researchers because of its considerable diversity in biological activities. The versatility of the thiophene nucleus is demonstrated by the successful introduction of its derivatives, which have anti‐inflammatory (Thenaldine), anticancer (Ralitrexed), antioxidant (Erdosteine), and antimicrobial (Cefoxitin and Temocillin) activities. This decent variety in the biological response profile has pulled in the consideration of numerous researchers to research this skeleton to its distinctive potential against several activities. This review is integral to prior reviews and plans to review the work regarding antibacterial and antifungal activities of thiophene, substituted thiophene and thiophene‐like compounds, and also Schiff bases of thiophene and substituted thiophenes from year 1995 to the beginning of 2018.     

A highly potent and selective PKCalpha inhibitor generated via combinatorial modification of a peptide scaffold

A potent and highly selective inhibitor of protein kinase C alpha has been generated via the combinatorial modification of a consensus sequence peptide. The inhibitor displays a Ki of 800 pM versus variable peptide substrate and good selectivity versus other members of the PKC family, including PKCbeta (385-fold), PKCgamma (580-fold), PKCdelta (2730-fold), PKCepsilon (600-fold), PKCeta (1310-fold), PKCtheta (1210-fold), PKCiota (940-fold), and PKCzeta (640-fold). The parallel synthesis strategy employed is easily automated and straightforward to implement.     

Synthesis and pharmacological activity of diterpenylnaphthoquinone derivatives

New diterpenylquinones, combining a diterpene diacid and a naphthoquinone, were prepared from junicedric acid and lapachol. The new derivatives were assessed as gastroprotective agents by the HCl-EtOH-induced gastric lesions model in mice as well as for basal cytotoxicity on the following human cell lines: Normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), and hepatocellular carcinoma (Hep G2). Several of the new compounds were significantly active as antiulcer agents and showed selective cytotoxicity against AGS cells.     

A solid-phase, library synthesis of natural-product-like derivatives from an enantiomerically pure tetrahydroquinoline scaffold

With the goal of developing a library synthesis of tetrahydroquinoline-derived natural-product-like small molecules, a practical synthesis of enantiomerically pure tetrahydroquinoline scaffold was achieved. An asymmetric aminohydroxylation reaction was the key step in this strategy. This scaffold was further immobilized onto the solid support for the library generation. The library was obtained from three diversity sites: (i) acylation of the hydroxyl group (R(1)), (ii) coupling of the Fmoc-protected amino acid to the amino group (R(2)), and (iii) amidation of the N-terminal amine group (R(3)).     

Polygodial: A viable natural product scaffold for the rapid synthesis of novel polycyclic pyrrole and pyrrolidine derivatives

The dialdehyde polygodial was utilised as a chiral scaffold for the unified synthesis of novel polycyclic pyrrole and pyrrolidine derivatives. Mechanistic insight into the reaction of primary amines with this dialdehyde was obtained. In addition, one of these polycyclic pyrroles was transformed further to prepare novel pentacyclic frameworks.     

Syringaldehyde as a scaffold for the synthesis of some biologically potent heterocycles

Syringaldehyde was utilized in synthesis of different heterocyclic systems. Some of the synthesized compounds 2 , 7 , 8 , 10 , 11 , and 13 were tested for antioxidant activity where they showed ability to inhibit oxidation in kidney and rat brain homogenates using 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Also, the activity against cancer was examined using the standard MTT method for two human tumor cell lines namely; mammary gland breast cancer MCF-7 and hepatocellular carcinoma HepG2. The highest activity as antioxidant and antitumor agents was exhibited by compounds 8 and 11 . However, moderate activities were shown by compounds 10 and 13 . While, compounds 2 , 7 showed weak activities.     

Synthesis and pharmacological activity evaluation of curcumin derivatives

Curcumin 3,4-dihydropyrimidinones/thiones/imines have been synthesized using one-pot cyclocondensation of curcumin with substituted aromatic aldehydes and urea/thiourea/guanidine in the presence of chitosamine hydrochloride as a biodegradable and nontoxic catalyst under solvent-free microwave irradiation. The synthesized product was purified by crystallization from ethanol and the process does not involve any hazardous solvent. All the synthesized curcumin derivatives 4a-o were screened for antioxidant and anti-inflammatory activity. Biological activity data of the synthesized showed that most of the synthesized compounds exhibited greater antioxidant and anti-inflammatory activity than curcumin.     

X-ray structures and pharmacological activities of lidocaine derivatives

The molecular and crystal structures of the lidocaine analogs 2-(pyrazol-1-yl)-2′-methylacetanilide (1), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-2′-methylacetanilide (2), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-3′-methylacetanilide (3), and 2-(pyrazol-1-yl)-4′-methylacetanilide (4), are reported, with a summary of their pharmacological activities. In this series, the moiety comprising the heterocyclic ring and the amide alkyl linker displays a common conformation. Molecules of 1–4 form identical hydrogen bonded motifs in their crystals, namely linear chains via intermolecular N–H···O=C hydrogen bonding. Moderate anesthetic and anti-arrhythmic potencies recorded for 1–4 relative to lidocaine are countered by their significantly lower toxicities.     

Synthesis of novel phthalazine derivatives as pharmacological activities

Phthalazine derivatives attached to amino acid derivatives were synthesized with high yields. The reaction of phthalazine derivatives with different phthalyl and tosylamino acids such as glycine, alanine, phenylalanine, valine, serine, and threonine in the presence of N,N-dicyclo hexylcarbodiimide (DCC) as a dehydrating agent reagent yielded high yields of the afforded compounds. Phthalylamino acids derivatives were obtained by deprotection of phthalazine derivatives, with the latter heating with hydrazine hydrate. The chemical structures of all phthalazine derivatives were affirmed by elemental analysis and spectral data (IR, MS, ¹HNMR, and ¹³C NMR). Screening out and estimation of the synthesized derivatives for their cytotoxic and antioxidant activity were done, and most of them showed powerful activity in comparison with standard drugs.     

Charge control of phenol complexation with unsaturated compounds containing organosilicon substituents. Thiophene derivatives

The frequency shifts of the O-H stretching modes and the resonance components _R of these shifts in the IR spectra of H-complexes of phenol with thiophene derivatives having organic and organosilicon substituents have been analyzed. Relationship of and _R parameters to values calculated by nonempirical methods that characterize the electronic effect of organic substituents on the effective charges of the thiophene ring atoms has been established. It has been shown that in the complexation of phenol (hard acid) with thiophene derivatives charge control prevails over frontier orbital control. The changes in the effective charges of the thiophene ring atoms due to the effect of organosilicon substituents have been calculated.For the previous publication of this series see Ref. 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2163–2168, December, 1994.This work was supported by the Russian Foundation for Basic Research, Project No. 93-03-18725.