Synthesis Of New Thieno Research Articles

New modified thieno[2,3-d]pyrimidine derivatives as VEGFR-2 inhibitors: Design, synthesis, in vitro anti-cancer evaluation and divers in silico studies

Angiogenesis is a critical regulatory mechanism for tumor development and metastasis. Tumor growth is closely related to the production of the vascular endothelial growth factor (VEGF), which is mediated by the cell-surface kinase VEGFR-2. Accordingly, blocking of VEGFR-2 is an important approach to find new treatments for malignancies. The aim of this research is the synthesis of new thieno[2,3-d]pyrimidine derivatives that could be potential anticancer leads inhibiting VEGFR-2. The prepared thieno[2,3-d]pyrimidine derivatives were tested in vitro for their inhibitory effects against the kinase activity of VEGFR-2. In addition, the synthesized compounds were assessed for their anti-proliferative activities against MCF-7 and HepG2 cell lines. Compound 4c displayed the strongest anti-VEGFR-2 potentiality with an IC50 value of 0.15 µM and exhibited good anti-proliferative effects against HepG2 and MCF-7 cells with IC50 of 17.14 and 11.56 µM, respectively. Compound 4c induced cell cycle arrest at the S phase and boosted early and late apoptosis in MCF-7 cells. Additionally, compound 4c increased BAX (4.5-fold), decreased Bcl-2 (3.5-fold), and demonstrated a notable increase in caspase-8 (2.9-fold) and caspase-9 (3.3-fold) levels. Furthermore, compound 4c significantly reduced TNF-α (3.6-fold) and IL-6 (3.2-fold) levels in MCF-7 cells. Molecular docking studies indicated good binding affinities as well as energies of the thieno[2,3-d]pyrimidine derivatives against the VEGFR-2. Molecular dynamics (MD) simulations were utilized to study the structural, energetic, and conformational changes of the VEGFR-2–4c complex, and the results indicated its stability. The MM-GBSA study of the VEGFR-2–4c complex showed a stable thermodynamic behavior with a binding free energy of -44 kcal/mol. The PLIP analysis identified the 3D interactions and binding conformation through the VEGFR-2–4c complex. Moreover, the DFT studies have been performed to study, Mullikan atomic charge distribution, FMO, ESP, the total density of state, and the QTAIM maps of compound 4c to theoretically verify its reactivity. Finally, computational ADMET and toxicity studies were conducted to assess the drug development potential of the thieno[2,3-d]pyrimidine derivatives.

Synthesis of New Thieno[2,3-b]pyridine Derivatives Based on Fused Thiophenes

Conditions for the Gewald synthesis of 2-amino-5,5-dimethyl-4,7-dihydro-5H-thieno[2,3-c]pyrans from 2,2-dimethyltetrahydropyran-4-ones have been optimized, and the yields have been improved. A procedure has been developed for the synthesis of new pyrano[4′,3′:4,5]thieno[2,3-b]pyridines by the Thorpe–Ziegler reaction of thieno[2,3-c]pyrans. Anticonvulsant activity of the synthesized compounds was studied.

Synthesis of New Thieno[3, 2‐b]pyridines and Thieno[2, 3‐b]pyrazines by Palladium Cross‐Coupling.

AbstractSeveral new 3‐(hetero)aryl‐2‐phenylthieno[3, 2‐b]pyridines and 7‐(hetero)aryl‐6‐phenyl thieno[2, 3‐b]pyrazines were prepared by Suzuki cross‐coupling of 3‐bromo‐2‐phenylthieno[3, 2‐b]pyridine and 7‐bromo‐6‐phenylthieno[2, 3‐b]pyrazine and (hetero)arylboronic acids after optimization of the reaction conditions, in moderate to excellent yields. The 3‐ and 7‐brominated compounds were prepared by bromination using Br2 in CH2Cl2 at 0 °C of the 2‐phenylthieno[3, 2‐b]pyridine and 6‐phenylthieno[2, 3‐b]pyrazine, respectively. The latter were synthesized in a two‐step one‐pot procedure by Pd/Cu catalyzed Sonogashira coupling of 2‐bromo‐3‐chloropyridine or 2,3‐dichloropyrazine with phenylacetylene, followed by treatment with Na2S. We show the wide scope of the synthesis of Suzuki cross‐coupling products, after optimization of the reaction conditions, from both brominated biheterocyclic systems and different (hetero)arylboronic acids. The final compounds may show interesting biological activity.

Synthesis of new thieno[2,3-b]pyridine derivatives as pim-1 inhibitors

Three series of 5-bromo-thieno[2,3-b]pyridines bearing amide or benzoyl groups at position 2 were prepared as pim-1 inhibitors. All the prepared compounds were tested for their pim-1 enzyme inhibitory activity. Two compounds (3c and 5b) showed moderate pim-1 inhibitory activity with IC50 of 35.7 and 12.71 μM, respectively. Three other compounds (3d, 3g and 6d) showed poor pim-1 inhibition. The most active compounds were tested for their cytotoxic activity on five cell lines [MCF7, HEPG2, HCT116, A549 and PC3]. Compound 3g was the most potent cytotoxic agent on almost all the cell lines tested.

ChemInform Abstract: Efficient Synthesis of New Thieno[2,3‐d]pyrimidin‐4(3H)‐one Derivatives for Evaluation as Anticancer Agents.

AbstractSome of the new compounds (IV) show good cytotoxicity against human breast and lung cancer cell lines, with compound (IVf) possessing the best inhibitory activity against lung cancer cell line (A459).

Efficient Synthesis of New Thieno[2,3‐d]pyrimidin‐4(3H)‐one Derivatives for Evaluation as Anticancer Agents

Thieno[2,3‐d]pyrimidinones were reported to act as potent anticancer agents; in this work, a series of new substituted thieno[2,3‐d]pyrimidinone (6) were synthesized via the aza‐Wittig reaction in satisfactory yields. The structures of these compounds were confirmed by elemental analysis, IR, 1H‐NMR, and mass spectral data, and compound 6h was further analyzed by single crystal X‐ray diffraction. Cytotoxic effect of all the compounds was carried out on human breast and lung cancer cell lines (MCF‐7 and SPC‐A‐1, A459). Compound 6f exhibited the best inhibition activities against A459 with IC50 4.1 μM.

DBU Promoted Facile Synthesis of New Thieno[2,3‐b]pyridine/quinoline Derivatives and Their Antimicrobial Evaluation

Several new thieno[2,3‐b]pyridine and thieno[2,3‐b]quinoline derivatives are synthesized in an efficient manner catalyzed by DBU as a base. Simple workup procedure, good yields, and mild reaction conditions are the salient features of this method. All the synthesized compounds are screened for antimicrobial activity against several organisms.

Facile and Convenient Synthesis of New Thieno[2,3-b]-Thiophene Derivatives

A facile and convenient synthesis of bis(2-(1H-benzo[d]imidazol-2(3H)-ylidene)-3-oxopropanenitrile), bis((3-amino-5-(methylthio)-1H-pyrazol-4-yl)methanone) and bis(2-thioxo-1,2-dihydropyrimidine-5-carbonitrile) derivatives incorporating a thieno- [2,3-b]thiophene moiety via versatile, readily accessible diethyl 3,4-dimethylthieno-[2,3-b]thiophene-2,5-dicarboxylate (1) is described.

ChemInform Abstract: Synthesis of New Thieno[3,2‐b]pyridine Derivatives by Palladium‐Catalyzed Couplings and Intramolecular Cyclizations.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of new thieno[3,2- b]pyridine derivatives by palladium-catalyzed couplings and intramolecular cyclizations

Two methyl 3-aminothieno[3,2- b]pyridine-2-carboxylates were prepared from 3 -fluoro or 3-nitropicolinonitriles and methyl thioglycolate in DMF/KOH(aq). From the unsubstituted precursor in the pyridine ring, di(hetero)arylamines were obtained by C–N Buchwald–Hartwig coupling with bromonitrobenzenes and with 2-bromopyridine. In the latter case a tetracyclic compound was formed by intramolecular cyclization. Using a brominated derivative in the pyridine ring as a coupling component, it was possible to synthesize C–C (Suzuki and Sonogashira) and C–N (Buchwald–Hartwig) coupling products and a tetracyclic compound obtained by bifunctionalization of the thienopyridine system.

Synthesis of New Thieno‐ and Pyrazolo‐pyridazine Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of New Thieno- and Pyrazolo- pyridazine Derivatives

5,6-Di(pyridin-2-yl)-3-thioxo-2,3-dihydropyridazine-4-carbonitrile 2 has been reacted with ahalocompounds, such as chloroacetone, chloroacetamide, ethyl chloroacetate and chloroacetic acid gave the corresponding 2-S-alkylated pyridazine derivatives 3, 6, 10 and 13 which have been cyclised to give the corresponding thienopyridazine derivatives 4, 7, 11, and 14 respectively. Reaction of 15 with hydrazine hydrate gave the corresponding pyrazolopyridazine 16.

Synthesis of New Thieno[b]azepinediones from α‐Methylene Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of New Thieno[b]azepinediones from α-Methylene Ketones

New substituted 6,7-dihydro-4H-thieno[3,2-b]azepine-5,8-diones were synthesized in seven steps, starting from substituted u-methylene ketones, via 3-aminothiophene-2-carboxylic acid alkyl esters.

Synthesis of new thieno and pyrazolo[2,1]benzothiazepine derivatives with potential antidepressant properties

AbstractIn this paper we describe a series of new thieno and pyrazolo[2,1]benzothiazepine derivatives 7a‐o which were synthesized by two different methods both starting from the previously described tricyclic alcohols 1–3. Several components of this series were effective p. o. (per os, orally) in different pharmacological tests currently employed in the evaluation of antidepressant activity.

Synthesis of some new thieno[3,4‐d]pyrimidines and their C‐nucleosides

AbstractThe synthesis of several new thieno[3,4‐d]pyrimidine C‐nucleosides 5‐8 is described. The known 5‐ribosyl‐ated methyl 4‐(formylamino)thiophene‐3‐carboxylate key intermediate 20 was obtained as a mixture of anomers in significantly improved yield by condensation of the sugar 15 with methyl 4‐(formylamino)thio‐phene‐3‐carboxylate 19 in nitromethane at 60° in the presence of stannic chloride. Attempts to prepare the C‐7 ribosylated compound 21β by direct condensation of the bicyclic base 10 with 15 gave instead the N‐1 ribosylated nucleoside 16. The synthesis of the corresponding and previously unknown thieno[3,4‐d]pyrimi‐dine bases 12 and 13 is described along with stability studies on the 4‐methylthio derivative 12. Preliminary biological studies indicate that adenosine analogue 7 is a potent growth inhibitor of several mammalian tumor cell lines.

ChemInform Abstract: Synthesis of New Thieno(3,4‐c)thiophene Derivatives by Reaction of Diformyl Substituted Thieno(3,4‐c)thiophenes with Malononitrile and N,N‐Dimethylhydrazine.

ChemInformVolume 21, Issue 48 Heterocyclic Compounds ChemInform Abstract: Synthesis of New Thieno(3,4-c)thiophene Derivatives by Reaction of Diformyl Substituted Thieno(3,4-c)thiophenes with Malononitrile and N,N-Dimethylhydrazine. A. TSUBOUCHI, A. TSUBOUCHI Dep. Appl. Chem., Coll. Eng., Univ. Osaka Prefect., Sakai, Osaka 593, JapanSearch for more papers by this authorN. HAMASAKI, N. HAMASAKI Dep. Appl. Chem., Coll. Eng., Univ. Osaka Prefect., Sakai, Osaka 593, JapanSearch for more papers by this authorN. MATSUMURA, N. MATSUMURA Dep. Appl. Chem., Coll. Eng., Univ. Osaka Prefect., Sakai, Osaka 593, JapanSearch for more papers by this authorH. INOUE, H. INOUE Dep. Appl. Chem., Coll. Eng., Univ. Osaka Prefect., Sakai, Osaka 593, JapanSearch for more papers by this author A. TSUBOUCHI, A. TSUBOUCHI Dep. Appl. Chem., Coll. Eng., Univ. Osaka Prefect., Sakai, Osaka 593, JapanSearch for more papers by this authorN. HAMASAKI, N. HAMASAKI Dep. Appl. Chem., Coll. Eng., Univ. Osaka Prefect., Sakai, Osaka 593, JapanSearch for more papers by this authorN. MATSUMURA, N. MATSUMURA Dep. Appl. Chem., Coll. Eng., Univ. Osaka Prefect., Sakai, Osaka 593, JapanSearch for more papers by this authorH. INOUE, H. INOUE Dep. Appl. Chem., Coll. Eng., Univ. Osaka Prefect., Sakai, Osaka 593, JapanSearch for more papers by this author First published: November 27, 1990 https://doi.org/10.1002/chin.199048134Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue48November 27, 1990 RelatedInformation

ChemInform Abstract: Synthesis of New Thieno(3,4‐c)thiophene Derivatives Having Formyl Substituents.

AbstractThe known thienothiophene (I) reacts with Vilsmeier's reagent to give the aldehydes (III) and (IV).

Synthesis of new thieno[3,4-c]thiophene derivatives having formyl substituents

The relatively stable new thieno[3,4-c]thiophene derivatives, 1-formyl-3,4,6-tris(isopropylthio)thieno[3,4-c]thiophene (3) and 1,6-diformyl-3,4-bis(isopropylthio)thieno[3,4-c]thiophene (4), have been prepared from 1,3,4,6-tetrakis(isopropylthio)thieno[3,4-c]thiophene (2) by substitution with the Vilsmeier reagent, and the structure of (4) has been determined by X-ray diffraction.