Chemistry:Sarecycline
Sarecycline, sold under the brand name Seysara, is a narrow-spectrum tetracycline-derived antibiotic medication.[1][2] It is specifically designed for the treatment of acne, and was approved by the FDA in October 2018 for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older.[3] Two randomized and well-controlled clinical trials reported efficacy data on both facial and truncal acne (back and chest).[4] Efficacy was assessed in a total of 2002 subjects 9 years of age and older.[3] Unlike other tetracycline-class antibiotics, sarecycline has a long C7 moiety that extends into and directly interact with the bacterial messenger RNA (mRNA) via hydrogen bonding of the oxygen atom in the N-oxide moiety to nucleotide residues.[5] The spectrum of activity is limited to clinically relevant Gram-positive bacteria, mainly Cutibacterium acnes, with little or no activity against Gram-negative bacterial microflora commonly found in the human gastrointestinal tract.[6]
Medical uses
Sarecycline, is indicated for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris.[3]
Synthesis
The chemical synthesis of sarecycline was reported:[7]
The iodination of sancycline [808-26-4] (1) with N-iodosuccinimide gave 7-iodotetracycline [113164-67-3] (2). Carbonylation catalyzed by palladium acetate and Xantphos followed by treatment with triethylsilane provided the corresponding aldehyde [1035655-10-7] (3). Reductive amination with methoxymethylamine [1117-97-1] using sodium cyanoborohydride as the reductant provided an overall yield of 23% of sarecycline (4).
References
- ↑ "Microbiological Profile of Sarecycline, a Novel Targeted Spectrum Tetracycline for the Treatment of Acne Vulgaris". Antimicrobial Agents and Chemotherapy 63 (1). January 2019. doi:10.1128/AAC.01297-18. PMID 30397052.
- ↑ "Sarecycline". U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/54681908.
- ↑ 3.0 3.1 3.2 Cite error: Invalid
<ref>tag; no text was provided for refs namedSeysara FDA label - ↑ "Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials". Journal of Drugs in Dermatology 17 (9): 987–996. September 2018. PMID 30235387.
- ↑ "Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome". Proceedings of the National Academy of Sciences of the United States of America 117 (34): 20530–20537. August 2020. doi:10.1073/pnas.2008671117. PMID 32817463. Bibcode: 2020PNAS..11720530B.
- ↑ "Microbiological Profile of Sarecycline, a Novel Targeted Spectrum Tetracycline for the Treatment of Acne Vulgaris". Antimicrobial Agents and Chemotherapy 63 (1). January 2019. doi:10.1128/AAC.01297-18. PMID 30397052.
- ↑ "Synthetic Approaches to New Drugs Approved during 2018". Journal of Medicinal Chemistry 63 (19): 10652–10704. 8 October 2020. doi:10.1021/acs.jmedchem.0c00345. https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00345.
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