Design and synthesis of some thieno[2,3-c]pyridazine derivatives of expected anticancer activity (original) (raw)
Related papers
Facile Synthesis of Some Novel Pyrido[3', 2': 4, 5]thieno[2,3-b][1,4]thiazine-8-carboxylic Acids
Molecules, 2007
Model tetrahydropyrido[3',2':4,5]thieno[2,3-b][1,4]thiazines 9a-c were synthesized via reductive lactamization, using sodium dithionite, of the respective 2-[(carboxyalkyl)thio]-3-nitro-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acids 7a-c. The latter derivatives were made via interaction of 2-chloro-7-cyclopropyl-3-nitro-4,7dihydrothieno[2,3-b]pyridine-5-carboxylic acid (6) with each of α-mercaptoacetic, αmercaptopropionic, and α-mercaptosuccinic acids and triethylamine in aqueous acetone at room temperature. The structures of 7a-7c and 9a-9c are supported by microanalytical and spectral (IR, MS, NMR) data. Compounds 9a and 9c showed potent inhibitory activity against the IGROV1 (Ovarian Cancer) cell line.
Journal of Heterocyclic Chemistry, 2019
On the basis of the proven activity of thieno[2,3-b]pyridines as anticancer, we have designed to synthesize a novel several heterocyclic compounds utilizing thieno[2,3-b]pyridine as a skeleton through various chemical reactions. The synthesized compounds bear rings that are either directly attached to the thieno[2,3-b]pyridine as in compounds 4 to 6 and 9 or connected through an amide bridge as compounds 2, 3a-b, 7, and 8. As well as, compounds 10, 12 to 28, 30, 31, and 33 to 36 bear fused rings to the thieno[2,3-b]pyridine backbone. The newly synthesized compounds were screened for their antiproliferative activity in vitro against hepatocellular carcinoma (HepG-2) and breast cancer (MCF-7) compared with the standard drug (doxorubicin). Compounds 3b, 4, 6, 22, and 28 exhibited promising growth inhibitory effect toward both HepG-2 and MCF-7 cell lines with IC 50 values ranging from 5.88 to 11.70 μg/ mL and 9.64 to 15.10 μg/mL, respectively.
Journal of Heterocyclic Chemistry, 2019
Ring opening reactions of benzoxazinones (6a,b) with oxygen, nitrogen and carbon nucleophiles gave the corresponding benzoates (7), benzamides (8), acrylamides (9 and 11) and the cyanoacetamides (10 a,b). Condensation of compounds (6) with amines under drastic conditions, Yield:ed the quinazolinone derivatives (13). When reacted with thiosemicarbazide and/or phenyl thiourea, compound 6b gave the triazole (14) and / or pyrimidoquinazolinone (15). Some of the new compounds (7a, 7b, 7c, 8b, 8d, 9, 11, 13a, 13b, 14 and 15) were tested for cytotoxic activity using tumor cell line (MCF7).
SYNTHESIS OF NEW PYRIDO [3',2':4,5]THIENO[2,3-e]PYRROLO[1,2-a]PYRAZINES
Heterocyclic Communications, 2003
The aim of the present paper is to describe the synthesis of several unknown polyfused heterocycles containing the pyrazine ring. Novel pyrido[3',2':4,5]thieno[2,3-e]pyiTolo[l,2-a]pyrazines derivatives have been synthesized starting from methyl 3-amino thieno[2,3-b] pyridines carboxylates via a Curtius rearrangement.
Acta Chimica Slovenica, 2021
A new series of substituted ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a-e were prepared by utilizing ethyl 2-chloro-7-cyclopropyl-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate (1) and replacing of the 2-chlorine with anions obtained from phenol (2a), salicylaldehyde derivatives 2b-d or thiophenol (2e), leading to the respective ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a-e. The new compounds were evaluated for their in vitro cytotoxicity towards sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. The screening revealed that compounds 3a, 3b, and 3e inhibited the growth of both cell lines. Compound 3b, with a phenol moiety, exhibited the highest growth inhibitory activity against CEM/ADR5000 and CCRF-CEM cells with IC 50 values 4.486 ± 0.286 and 2.580 ± 0.550 µM, respectively. Collectively, the presented results demonstrate that the synthesized thieno[2,3-b]pyridines warrant further exploration for potential use as anti-cancer agents.
Thieno[2,3- d ]pyrimidines in the Synthesis of Antitumor and Antioxidant Agents
Archiv Der Pharmazie, 2010
Dimethyl acetylenedicarboxylate, ethyl propiolate, and E-dibenzoylethylene react with thienopyrimidines (cyclo-pentyl, -hexyl, and -heptyl) derivatives to form thiazolo[3,2-a]thieno-[2,3-d]pyrimidin-2-ylidene) acetates, thieno[2,3-d]pyrimidin-2-ylthioacrylates, and thieno[2′,3′:4,5]pyrimido[2,1-b][1,3]thiazin-6-ones, respectively. Reactions proceed via cyclization and thio-addition processes. Some derivatives of thienopyrimidines showed high inhibition of Hep-G2 cell growth compared with the growth of untreated control cells. However, the fused heptyl of thienopyrimidothiazines indicates a promising specific antitumor agent against Hep-G2 cells with IC50 < 20 μM.
Tetrahedron, 1999
3-Alkylamino-pyrido[4,3-el-l.2.4-thiadiazine 1,1-dioxide represents a new class of heterocyclic compounds expressing important pharmacological properties. According to the position of the C=N double bond in the thiadiazine ring, this heterocyclic ring system may exist under three different tantomeric forms. 13)' means of spectral and X-ray data collected from selected compounds, the most favourable tautomeric form adopted by 3-alkylamino-pyrido[4,3-e]-l,2,4-thiadiazine 1,l-dioxides devoid of an alkyl substituent in the 2-or in the 4-position was determined. The present study giving new insights in the geometrical and conformational ~s of pyridothiadiazinedioxides is important considering the pharmacological potentialities of this class of heterocyclic compounds.
Design and Synthesis of Pyridazine Containing Compounds with Promising Anticancer Activity
Chemical & pharmaceutical bulletin, 2017
Certain pyridazine containing compounds 2a-f, 3a, b, 4a, b, 5a, b, 6a and b were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were screened for their cytotoxic activity in vitro on colon cancer cell line (HCT-116) and breast cancer cell line (MCF-7). In addition, the antitumor activity of the synthesized compounds was tested in vivo against Ehrlich's ascites carcinoma (EAC) solid tumor grown in mice. The in vitro vascular endothelial growth factor receptor (VEGFR) enzyme inhibition assay was carried out for the most active compounds at a single dose of 10 µM. The obtained results revealed that compound 5b, which showed potent cytotoxic activity against HCT-116 also, exhibited the highest inhibition in the VEGFR kinase assay (92.2%).