CEFILAVANCIN

CEFILAVANCIN, TD-1792

CAS 722454-12-8

C₈₇H₉₆Cl₃N₁₆O₂₈S₂, _1984.28

F76229E21M

Vancomycin, 26-[[[3-[[(Z)-[1-(2-amino-5-chloro-4-thiazolyl)-2-[[(6R,7R)-2-carboxy-8-oxo-3-(pyridiniomethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]amino]-2-oxoethylidene]amino]oxy]propyl]amino]carbonyl]-26-decarboxy-

1-{[(6R,7R)-7-[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-[(3-{[(1S,2R,18R,19R,22S,25R,28R,40S)-48-{[(2S,3R,4S,5S,6R)-3-{[(2S,4S,5S,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl]oxy}-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-22-(carbamoylmethyl)-5,47-dichloro-2,18,32,35,37-pentahydroxy-19-[(2R)-4-methyl-2-(methylamino)pentanamido]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2^{3,6}.2^{14,17}.1^{8,12}.1^{29,33}.0^{10,25}.0^{34,39}]pentaconta-3,5,8,10,12(48),14,16,29(45),30,32,34(39),35,37,46,49-pentadecaen-40-yl]formamido}propoxy)imino]acetamido]-2-carboxylato-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl}pyridin-1-ium

Phase III Skin and soft tissue infections

• OriginatorGlaxoSmithKline; Theravance
• DeveloperR-Pharm; Theravance Biopharma
• ClassAcetamides; Antibacterials; Azabicyclo compounds; Beta-lactams; Cephalosporins; Peptide antibiotics; Pyridines; Thiazoles
• Mechanism of ActionCell wall inhibitors

BUILDING BLOCK

Vancomycin,

• 1404-90-6 

• 31 Jan 2020Cefilavancin is still in phase III trials for Skin and soft tissue infection in Russia and Georgia (R-Pharm pipeline, January 2020)
• 17 Jun 2015Phase II development is ongoing the USA
• 02 Jun 2014Theravance Biopharma is formed as a spin-off of Theravance

SCHEME

SYN

WO2003031449

https://patentscope.wipo.int/search/en/WO2003031449

cheme A

REF

Li, Huijuan; ET AL, Medicine (Philadelphia, PA, United States) (2022), 101(34), e30120

References

1. ^ Long DD, Aggen JB, Chinn J, Choi SK, Christensen BG, Fatheree PR, et al. (October 2008). “Exploring the positional attachment of glycopeptide/beta-lactam heterodimers”. The Journal of Antibiotics. 61 (10): 603–614. doi:10.1038/ja.2008.80. PMID 19168974.
2. ^ Tyrrell KL, Citron DM, Warren YA, Goldstein EJ (April 2012). “In vitro activity of TD-1792, a multivalent glycopeptide-cephalosporin antibiotic, against 377 strains of anaerobic bacteria and 34 strains of Corynebacterium species”. Antimicrobial Agents and Chemotherapy. 56 (4): 2194–2197. doi:10.1128/AAC.06274-11. PMC 3318369. PMID 22290981.
3. ^ Stryjewski ME, Potgieter PD, Li YP, Barriere SL, Churukian A, Kingsley J, et al. (November 2012). “TD-1792 versus vancomycin for treatment of complicated skin and skin structure infections”. Antimicrobial Agents and Chemotherapy. 56 (11): 5476–5483. doi:10.1128/aac.00712-12. PMC 3486540. PMID 22869571.
4. ^ Douglas EJ, Laabei M (September 2023). “Staph wars: the antibiotic pipeline strikes back”. Microbiology. 169 (9). Reading, England. doi:10.1099/mic.0.001387. PMC 10569064. PMID 37656158.
5. ^ Surur AS, Sun D (2021). “Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates”. Frontiers in Chemistry. 9: 659845. Bibcode:2021FrCh….9..317S. doi:10.3389/fchem.2021.659845. PMC 8120311. PMID 33996753.
6. ^ Saxena D, Maitra R, Bormon R, Czekanska M, Meiers J, Titz A, et al. (December 2023). “Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens”. npj Antimicrobials and Resistance. 1 (1): 17. doi:10.1038/s44259-023-00016-1. PMC 11721184. PMID 39843585.
7. ^ Koh AJ, Thombare V, Hussein M, Rao GG, Li J, Velkov T (2023). “Bifunctional antibiotic hybrids: A review of clinical candidates”. Frontiers in Pharmacology. 14: 1158152. doi:10.3389/fphar.2023.1158152. PMC 10313405. PMID 37397488.
8. ^ Homer JA, Johnson RM, Koelln RA, Moorhouse AD, Moses JE (2024). “Strategic re-engineering of antibiotics”. Nature Reviews Bioengineering. doi:10.1038/s44222-024-00250-w.

////////////CEFILAVANCIN, TD-1792, TD 1792, F76229E21M, цефилаванцин, 头孢拉凡星, سيفيلافانسين , GlaxoSmithKline, Theravance, PHASE 3