188586-91-6Relevant academic research and scientific papers
Design, synthesis and biological evaluation of non-covalent AmpC β-lactamases inhibitors
Genovese, Filippo,Lazzari, Sandra,Venturi, Ettore,Costantino, Luca,Blazquez, Jesus,Ibacache-Quiroga, Claudia,Costi, Maria Paola,Tondi, Donatella
, p. 975 - 986 (2017/04/14)
Abstract: Bacterial resistance represents a worldwide emergency threatening the efficacy of all available antibiotics. Among the several resistance mechanisms developed by bacteria, β-lactamase enzymes?(BLs), which are able to inactivate most β-lactam core antibiotics, represent a key target to block, thus prolonging antibiotics half-life. Several approaches aimed at inhibiting β-lactamases have been so far undertaken, mainly involving β-lactam-like or covalent inhibitors. Applying a structure-based de novo design approach, we recently discovered a novel, non-covalent and competitive inhibitor of AmpC β-lactamase:?lead 1. It has a Ki of 1 μM, a ligand efficiency of 0.38 kcal mol?1 and lead-like physical properties. Moreover, it reverts resistance to ceftazidime in bacterial pathogens expressing AmpC and does not up-regulate β-lactamases expression in cell culture. Its features make it a good candidate for chemical optimization: starting from lead 1 crystallographic complex with AmpC, 11 analogs were designed to complement additional AmpC sites, then synthesized and tested against clinically resistant pathogens. While the new inhibitors maintain similar in vitro activity as the starting lead, some of them, in biological assays, extert a higher potency showing improved synergic activity with ceftazidime in resistant clinically isolated strains. Graphical Abstract: [InlineMediaObject not available: see fulltext.].
Novel carboxaldehyde mediated synthetic pathway for 5′-amino adenosine analogues
Gibbons, Garrett S.,Showalter, Hollis D.,Nikolovska-Coleska, Zaneta
, p. 348 - 360 (2015/05/05)
Modifications of the 5′-position of adenosine have been prepared via a novel 5′-carboxaldehyde synthon. The described methodology should prove useful for making related compounds in which amine-derived moieties off the 5′-position of adenosine (or related nucleoside congeners) can be easily incorporated via reductive amination, especially for the incorporation of aromatic amines.
GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Paragraph 0425; 0427, (2015/06/24)
Disclosed are a gonadotropin releasing hormone receptor antagonist and a pharmaceutical composition including the same, which can be useful in preventing or treating a sex hormone-related disease such as endometriosis, amenorrhea, irregular menstruation, uterine myoma, uterine fibroids, polycystic ovarian disease, lupus erythematous, hypertrichosis, precocious puberty, short stature, acne, alopecia, gonadal steroid-dependent neoplasms, gonadotropin-producing pituitary adenoma, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hyperplasia, contraception, and infertility, as well as Alzheimer disease.
GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Page/Page column 87; 88, (2013/09/12)
The present invention provides gonadotropin releasing hormone receptor antagonists and the pharmaceutical composition comprising the same, which can be useful in preventing or treating a sex hormone-related disease such as endometriosis, amenorrhea, irregular menstruation, uterine myoma, uterine fibroids, polycystic ovarian disease, lupus erythematous, hypertrichosis, precocious puberty, short stature, acne, alopecia, gonadal steroid-dependent neoplasms, gonadotropin-producing pituitary adenoma, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hyperplasia, contraception, and infertility, as well as Alzheimer disease
