- Ketorolac derivative, pharmaceutical composition and preparation method and application thereof
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The present invention provides a ketorolac derivative shown in formula (I), a pharmaceutical composition and a method and application thereof. As a drug, the ketorolac derivative has better half-life, stability, good pharmacokinetic properties, high stabi
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Paragraph 0254-0257; 0262-0265; 0270-0273; 0286-0289
(2022/01/08)
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- New orally active dual enkephalinase inhibitors (DENKIs) for central and peripheral pain treatment
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Protecting enkephalins, endogenous opioid peptides released in response to nociceptive stimuli, is an innovative approach for acute and neuropathic pain alleviation. This is achieved by inhibition of their enzymatic degradation by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptidase N (APN, EC 3.4.11.2). Selective and efficient inhibitors of both enzymes, designated enkephalinases, have been designed that markedly increase extracellular concentrations and half-lives of enkephalins, inducing potent antinociceptive effects. Several chemical families of Dual ENKephalinase Inhibitors (DENKIs) have previously been developed but devoid of oral activity. We report here the design and synthesis of new pro-drugs, derived from co-drugs combining a NEP and an APN inhibitor through a disulfide bond with side chains improving oral bioavailability. Their pharmacological properties were assessed in various animal models of pain targeting central and/or peripheral opioid systems. Considering its efficacy in acute and neuropathic pain, one of these new DENKIs, 19-IIIa, was selected for clinical development.
- Poras, Hervé,Bonnard, Elisabeth,Dangé, Emilie,Fournié-Zaluski, Marie-Claude,Roques, Bernard P.
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supporting information
p. 5748 - 5763
(2014/08/05)
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- Cephalosporin ester derivatives
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A compound of the formula: STR1 wherein R1 is a hydrogen atom or a lower alkyl group; R2 is an unsubstituted or lower alkyl-substituted alicyclic alkyl group of 3 to 12 carbon atoms or a C3-6 alicyclic alkyl-substituted lower alkyl group or a pharmaceutically acceptable salt thereof, processes for preparing the same, a pharmaceutical composition thereof are provided. The compound has an improved absorbability and can be orally applied as antibiotics.
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