Synthesis of ertugliflozin from d-glucose

Triantakonstanti, Virginia V.; Andreou, Thanos; Koftis, Theoharis V.; Gallos, John K.

doi:10.1016/j.tetlet.2019.03.009

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…The first, ertugliflozin ( 44 ), was approved by the FDA in 2017 as a cocrystal formulation with 5-oxo-proline and launched in the USA in 2018. The commercial route from 2,3,4,6-tetra- O -benzyl- d -glucose (commercially available) together with descriptions of the other methods/routes considered and/or attempted was published in 2014 by Bowles et al from Pfizer, and a short synthesis, though not on a commercial scale, starting from d -glucose was published by Triantakonstanti et al in 2019 . In 2019, sotagliflozin ( 43 ) was approved in the EU as an adjunct oral therapy for adults with type I diabetes who could not achieve suitable glycemic control just using insulin.…”

Section: Full Discussion Of Resultsmentioning

confidence: 99%

“…The commercial route from 2,3,4,6-tetra-Obenzyl-D-glucose (commercially available) together with descriptions of the other methods/routes considered and/or attempted was published in 2014 by Bowles et al from Pfizer, 145 and a short synthesis, though not on a commercial scale, starting from D-glucose was published by Triantakonstanti et al in 2019. 146 In 2019, sotagliflozin (43) was approved in the EU as an adjunct oral therapy for adults with type I diabetes who could not achieve suitable glycemic control just using insulin. The third "flozin" in this classification was remogliflozin etaborate (44), which was approved in India in 2019 for the treatment of diabetes 2, though it was originated by Kissei in Japan and was in trials under GSK for use in diabetes 1 and 2.…”

Section: ■ Full Discussion Of Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019

Newman¹,

Cragg²

2020

J. Nat. Prod.

3,541

2,843

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For all approved therapeutic agents, the time frame has been extended to cover the almost 39 years from the first of January 1981 to the 30th of September 2019 for all diseases worldwide and from ∼1946 (earliest so far identified) to the 30th of September 2019 for all approved antitumor drugs worldwide. As in earlier reviews, only the first approval of any drug is counted, irrespective of how many "biosimilars" or added approvals were subsequently identified. As in the 2012 and 2016 reviews, we have continued to utilize our secondary subdivision of a "natural product mimic", or "NM", to join the original primary divisions, and the designation "natural product botanical", or "NB", to cover those botanical "defined mixtures" now recognized as drug entities by the FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/ or synthetic variations using their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over the time frame from 1946 to 1980, of the 75 small molecules, 40, or 53.3%, are N or ND. In the 1981 to date time frame the equivalent figures for the N* compounds of the 185 small molecules are 62, or 33.5%, though to these can be added the 58 S* and S*/NMs, bringing the figure to 64.9%. In other areas, the influence of natural product structures is quite marked with, as expected from prior information, the anti-infective area being dependent on natural products and their structures, though as can be seen in the review there are still disease areas (shown in Table 2) for which there are no drugs derived from natural products. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, we are still able to identify only two de novo combinatorial compounds (one of which is a little speculative) approved as drugs in this 39-year time frame, though there is also one drug that was developed using the "fragment-binding methodology" and approved in 2012. We have also added a discussion of candidate drug entities currently in clinical trials as "warheads" and some very interesting preliminary reports on sources of novel antibiotics from Nature due to the absolute requirement for new agents to combat plasmid-borne resistance genes now in the general populace. We continue to draw the attention of readers to the recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated"; thus we consider that this area of natural product research should be expanded significantly.

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Section: Full Discussion Of Resultsmentioning

confidence: 99%