In the course of studies on compounds with expected antiinflammatory and immunosuppressive activity a series of new derivatives of tetrahydro [1,3]-thiazine-4-one-6-carboxylic acid, tetrahydro [1,3]-thiazine-4,6-dione and 2-thiobarbituric acid have been synthetized. Several new and unexpected details of the chemical behavior of these compounds were revealed. The chemical structure of the new compounds was confirmed by degradation and identification of the decomposition products and spectral analysis. Pharmacologic analysis showed that some of the compounds exerted an antiinflammatory and immunosuppressive activity.
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RSC Adv
January 2025
Department of Organic Chemistry, University of Debrecen Egyetem Square 1 Debrecen 4032 Hungary
Domino Knoevenagel-cyclization reactions of styrene substrates, containing an -(-formyl)aryl subunit, were carried out with -substituted 2-cyanoacetamides to prepare tetrahydro-4-pyrano[3,4-]quinolone and hexahydrobenzo[]phenanthridine derivatives by competing IMHDA and IMSDA cyclization, respectively. The diastereoselective IMHDA step with α,β-unsaturated amide, thioamide, ester and ketone subunits as a heterodiene produced condensed chiral tetrahydropyran or thiopyran derivatives, which in the case of Meldrum's acid were reacted further with amine nucleophiles in a multistep domino sequence. In order to simplify the benzene-condensed tricyclic core of the targets and get access to hexahydro-1-pyrano[3,4-]pyridine derivatives, a truncated substrate was reacted with cyclic and acyclic active methylene reagents in diastereoselective Knoevenagel-IMHDA reactions to prepare novel condensed heterocyclic scaffolds.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of General Surgery, the Second Xiang-Ya Hospital, Central South University, Changsha 410011 China. Electronic address:
The transforming growth factor β (TGF-β) type 1 receptor (ALK5) plays a key role in tumor microenvironment. Small-molecule inhibitors of TGFβR1 provides a prospective approach for the treatment of malignant tumors. In this study, a series of 4-((3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)oxy)quinoline derivatives were identified as novel, potential TGFβR1 inhibitors.
View Article and Find Full Text PDFBioorg Med Chem
January 2025
School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, 4701 W. Thunderbird Road, Glendale, AZ 85308, USA. Electronic address:
Six pyridine analogs of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid-or CD3254 (11)-in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzo[d][1,2,3]triazole-5-carboxylic acid (CBt-PMN or 23) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), an FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Treatment with 1 often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay.
View Article and Find Full Text PDFOrg Lett
January 2025
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
The cascade reaction of 3-diazo-2-sulfonyliminoindolines and -methoxymethyl--[(trimethylsilyl)methyl]benzylamines generates 2-sulfonylimino-1',3',4',6'-tetrahydro-2'-spiro[indoline-3,5'-pyrimidine] and spiro[indoline-3,3'-pyrrolidine] derivatives simultaneously under the catalysis of TFA and blue light irradiation. Their formation mechanisms were proposed on the basis of isotope-labeled experiments and HRMS analysis of the controlled experiment mixture, showing new reaction pathways. The current reaction provides a new strategy for the synthesis of biologically important spiro[indoline-3,3'-pyrrolidine]-2-one derivatives.
View Article and Find Full Text PDFChem Pharm Bull (Tokyo)
December 2024
Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
Osteoporosis is treated with oral and parenteral resorption inhibitors and parenteral osteogenic drugs. However, orally active small-molecule osteogenic drugs are not clinically available. Natural coumarin derivatives, such as osthole, exert osteoblastogenic effects.
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