858677-31-3Relevant academic research and scientific papers
Novel Potent Proline-Based Metalloproteinase Inhibitors: Design, (Radio)Synthesis, and First in Vivo Evaluation as Radiotracers for Positron Emission Tomography
Kalinin, Dmitrii V.,Wagner, Stefan,Riemann, Burkhard,Hermann, Sven,Schmidt, Frederike,Becker-Pauly, Christoph,Rose-John, Stefan,Sch?fers, Michael,Holl, Ralph
supporting information, p. 9541 - 9559 (2016/11/11)
As dysregulation of matrix metalloproteinase (MMP) activity is associated with a wide range of pathophysiological processes like cancer, atherosclerosis, and arthritis, MMPs represent a valuable target for the development of new therapeutics and diagnostic tools. We herein present the chiral pool syntheses, in vitro evaluation, and SAR studies of a series of d- and l-proline- as well as of (4R)-4-hydroxy-l-proline-derived MMP inhibitors possessing general formula 1. Some of the synthesized hydroxamic acids were found to be potent MMP inhibitors with IC50 values in the nanomolar range, also demonstrating no off-target effects toward the other tested Zn2+-dependent metalloproteases (ADAMs and meprins). Utilizing the structure of the (2S,4S)-configured 4-hydroxyproline derivative 4, a selective picomolar inhibitor of MMP-13, the radiolabeled counterpart [18F]4 was successfully synthesized. The radiotracer's biodistribution in mice as well as its serum stability were evaluated for assessing its potential use as a MMP-13 targeting PET imaging agent.
3-(4-PIPERIDINE-1YLMETHYL-PHENYL)-PROPION ACID-PHENYLAMIDE-DERIVATIVES AND RELATED COMPOUNDS USED IN THE FORM OF MCH ANTAGONISTS (MELANINE CONCENTRATING HORMONE) FOR TREATING EATING DISORDERS
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Page/Page column 90, (2008/06/13)
The invention relates to amid compounds of general formula (I), wherein groups and residuals A, B, b, W, X, Y, Z, R1, R2 and R3 have significances given in a claim 1. In addition, said invention relates to drugs containing at least one type of inventive amid. Because of the antagonist activity of an MCH-receptor, the inventive drugs are suitable for treating metabolic disturbances and/or eating disorders, in particular adiposity, bulimia, anorexia, hyperphagia and diabetes.
