Tricyclic boronic acids as broad-spectrum serine and metallo-β-lactamase inhibitors with in vitro activity against acinetobacter baumannii : a patent evaluation (US 2025/0223303)

Krajnc, Alen (author)

Introduction With β-lactams remaining the most widely prescribed antibacterials worldwide, their continuing clinical efficacy remains an important therapeutic goal. Rapid spread of serine and metallo-ß-lactamases (SBLs and MBLs, respectively), which can inactivate β-lactams, is increasingly threatening this objective. Finding clinically useful inhibitors of MBLs, for which no FDA approved treatment currently exists, is of interest. Areas covered This article concisely reviews structurally novel xeruborbactam-inspired tricyclic boronates (reported in US 2025/0223303) with promising inhibitory activities in vitro. The literature search was conducted using SciFinder and Patentscope. By introducing novel thioether-based C5 sidechains onto the previously optimized bicyclic boronate core, the inventors explored novel chemical space yielding SBL/MBL inhibitors with seemingly improved activities against carbapenem-resistant (CR) Escherichia coli, Klebsiella pneumoniae, and, importantly, Acinetobacter baumannii, when used in combination with meropenem and/or biapenem (at least with respect to taniborbactam, i.e. boronate inhibitor in late-stage clinical development). Expert opinion Due to the major societal importance of β-lactams for modern medicine, and the clearly demonstrated clinical potential of functionalized cyclic boronates as potent dual-acting SBL/MBL inhibitors when used in combination therapies, there is ample opportunity and scope for continued investigation of this pharmacophore, particularly in the context of discovering new therapeutic options for CR infections.

• Language: English
• Keywords: antimicrobial resistance, boronic acids, β-lactamase inhibitors, β-lactamsserine and metallo-β-lactamase, combination therapy
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 19 str.
• Numbering: Vol. 36, no. 2
• PID: 20.500.12556/RUL-179113
• UDC: 615.015.8
• ISSN on article: 1744-7674
• DOI: 10.1080/13543776.2025.2602703
• COBISS.SI-ID: 261052419
• Publication date in RUL: 05.02.2026

Record is a part of a journal

• Title: Expert opinion on therapeutic patents
• Shortened title: Expert opin. ther. pat.
• Publisher: Informa Healthcare
• ISSN: 1744-7674
• COBISS.SI-ID: 521644825

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: odpornost na protimikrobna zdravila, boronske kisline, inhibitorji β-laktamaz, β-laktamazserin in metalo-β-laktamaza, kombinirana terapija, farmacevtska kemija, protimikrobna odpornost

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: J1-60023
• Name: Boj proti karbapenemazam z novimi terapevtiki, ki vsebujejo bor