β-Lactam Derivatives as Enzyme Inhibitors: Peptidic Derivatives of (RS)-2-Oxo-4-phenylazetidine-1-alkanoic Acids

Elriati, Ali; Achilles, Karin; Loose, Jutta; Otto, Hans‐Hartwig

doi:10.1007/s00706-007-0639-9

Cited by 2 publications

(1 citation statement)

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“…Elriati et al reported the synthesis of new β‐lactams, namely a set of compounds with no substituents at C‐3 and others with mono‐ and di‐halogenation at C‐3; however, when tested for PPE inhibition they showed very weak inhibition and no further tests with HNE were performed. These results are in agreement with the suggestion of S1 subsite specificity of elastase toward small hydrophobic substituents.…”

Section: Acylating Inhibitorsmentioning

confidence: 99%

Targeting COPD: advances on low‐molecular‐weight inhibitors of human neutrophil elastase

Lucas

Costa

Guedes

et al. 2011

Medicinal Research Reviews

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Chronic obstructive pulmonary disease (COPD) is a major increasing health problem and the World Health Organization (WHO) reports COPD as the fifth leading cause of death worldwide. COPD refers to a condition of inflammation and progressive weakening of the structure of the lung as well as irreversible narrowing of the airways. Current treatment is only palliative and no available drug halts the progression of the disease. Human neutrophil elastase (HNE) is a serine protease, which plays a major role in the COPD inflammatory process. The protease/anti-protease imbalance leads to an excess of extracellular HNE hydrolyzing elastin, the structural protein that confers elasticity to the lung tissue. Although HNE was identified as a therapeutic target for COPD more than 30 years ago, only Sivelestat (ONO-5046), an HNE inhibitor from Ono Pharmaceutical, has been approved for clinical use. Nevertheless, Sivelestat is only approved in Japan and its development in the USA was terminated in 2003. Other inhibitors in pre-clinical or phase I trials were discontinued for various reasons. Hence, there is an urgent need for low-molecular-weight synthetic elastase inhibitors and the present review discusses the recent advances on this field covering acylating agents, transition-state inhibitors, mechanism-based inhibitors, relevant natural products, and major patent disclosures.

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Section: Acylating Inhibitorsmentioning

confidence: 99%