Unprotected primary sulfonamide group facilitates ring-forming cascade en route to polycyclic [1,4]oxazepine-based carbonic anhydrase inhibitors

Sapegin, Alexander; Kalinin, Stanislav; Angeli, Andrea; Krasavin, Mikhail

doi:10.1016/j.bioorg.2017.11.014

Cited by 20 publications

(10 citation statements)

References 40 publications

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“…Moreover, compound 130 was 4975‐, 10‐, and 403‐fold selective for hCA II over hCA I, hCA IV, and hCA IX, respectively. Indeed, analogue 131 was found to be 7443‐, 9‐, and 489‐fold selective for hCA II over hCA I, hCA IV, and hCA IX, respectively 250 …”

Section: Drug Design and Development Strategies For Selective Caismentioning

confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

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190

166

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Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H + ions and play a crucial role in regulating many physiological processes. CAs are wellstudied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.

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Section: Drug Design and Development Strategies For Selective Caismentioning

confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

Self Cite

190

166

View full text Add to dashboard Cite

show abstract

“…The resulting trifluoromethylated heterocycles 3 have a benzo[ c ][1,5]oxazonine skeleton, and are not only medicinally attractive fluorine-containing heterocycles, 1 but also expanded variants of well-known [1,4]oxazepine pharmaceuticals. 15 Synthesis of the titled nine-membered compounds 3 were achieved from previously unknown trifluoromethylated benzoxazinanones 1 (six-membered ring) via a formal ring-expansion pathway under palladium catalysis. The reaction proceeded via the double decarboxylation (DDC) 16 of 1 and vinylethylene carbonates 2 followed by a [5 + 4] cycloaddition reaction.…”

Section: Introductionmentioning

confidence: 99%

Access to benzo-fused nine-membered heterocyclic alkenes with a trifluoromethyl carbinol moiety via a double decarboxylative formal ring-expansion process under palladium catalysis

et al. 2018

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“…The tumor-associated h CA-IX isoform was strongly inhibited by all the examined compounds, with IC 50 ranging between 4.4 and 23.7 nM with statistical significance ( p < 0.05) as compared to reference control. These high-activity data came superior over several reported hCA-IX inhibitors such as the polycyclic sulfonamides (IC 50 = 260–21.2 nM) [ 46 ] and close related aromatic sulfamates (IC 50 = 27,719–17.6 nM) [ 47 ]. On the other hand, the presented compounds were found, to a certain degree, comparable to some members of celecoxib-mimic sulfonamides as reported hCA-IX inhibitors (IC 50 = 640–5 nM) [ 48 ].…”

Section: Resultsmentioning

confidence: 73%

The Anticancer Activity for the Bumetanide-Based Analogs via Targeting the Tumor-Associated Membrane-Bound Human Carbonic Anhydrase-IX Enzyme

et al. 2020

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The membrane-bound human carbonic anhydrase (hCA) IX is widely recognized as a marker of tumor hypoxia and a prognostic factor within several human cancers. Being undetected in most normal tissues, hCA-IX implies the pharmacotherapeutic advent of reduced off-target adverse effects. We assessed the potential anticancer activity of bumetanide-based analogues to inhibit the hCA-IX enzymatic activity and cell proliferation of two solid cancer cell lines, namely kidney carcinoma (A-498) and bladder squamous cell carcinoma (SCaBER). Bumetanide analogues efficiently inhibit the target hCA-IX in low nanomolar activity (IC50 = 4.4–23.7 nM) and have an excellent selectivity profile (SI = 14.5–804) relative to the ubiquitous hCA-II isoform. Additionally, molecular docking studies provided insights into the compounds’ structure–activity relationship and preferential binding of small-sized as well as selective bulky ligands towards the hCA-IX pocket. In particular, 2,4-dihydro-1,2,4-triazole-3-thione derivative 9c displayed pronounced hCA-IX inhibitory activity and impressive antiproliferative activity on oncogenic A-498 kidney carcinoma cells and is being considered as a promising anticancer candidate. Future studies will aim to optimize this compound to fine-tune its anticancer activity as well as explore its potential through in-vivo preclinical studies.

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Unprotected primary sulfonamide group facilitates ring-forming cascade en route to polycyclic [1,4]oxazepine-based carbonic anhydrase inhibitors

Cited by 20 publications

References 40 publications

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Access to benzo-fused nine-membered heterocyclic alkenes with a trifluoromethyl carbinol moiety via a double decarboxylative formal ring-expansion process under palladium catalysis

The Anticancer Activity for the Bumetanide-Based Analogs via Targeting the Tumor-Associated Membrane-Bound Human Carbonic Anhydrase-IX Enzyme

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