185384-16-1Relevant articles and documents
Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping
Ji, Haitao,Li, Huiying,Martásek, Pavel,Roman, Linda J.,Poulos, Thomas L.,Silverman, Richard B.
supporting information; experimental part, p. 779 - 797 (2009/12/07)
Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopping. On the basis of the structure of lead molecule 6, fragment hopping effectively extracted the minimal pharmacophoric elements in the active site of nNOS for ligand hydrophobic and steric interactions and generated appropriate lipophilic fragments for lead optimization. More potent and selective inhibitors with better druglike properties were obtained within the design of 20 derivatives (compounds 7-26). Our structure - based inhibitor design for nNOS and SAR analysis reveal the robustness and efficiency of fragment hopping in lead discovery and structural optimization, which implicates a broad application of this approach to many other therapeutic targets for which known druglike small-molecule modulators are still limited.
Design, synthesis and SAR studies of tripeptide analogs with the scaffold 3-phenylpropane-1,2-diamine as aminopeptidase N/CD13 inhibitors
Shang, Luqing,Fang, Hao,Zhu, Huawei,Wang, Xuejian,Wang, Qiang,Mu, Jiajia,Wang, Binghe,Kishioka, Shiroh,Xu, Wenfang
experimental part, p. 2775 - 2784 (2009/08/15)
Aminopeptidase N (APN), belonged to metalloproteinase, is an essential peptidase involved in the process of tumor invasion and metastasis. A series of tripeptide analogs with the scaffold 3-phenylpropane-1,2-diamine were designed, synthesized and evaluate
Synthesis and evaluation of inhibitors of cytochrome P450 3A (CYP3A) for pharmacokinetic enhancement of drugs
Flentge, Charles A.,Randolph, John T.,Huang, Peggy P.,Klein, Larry L.,Marsh, Kennan C.,Harlan, John E.,Kempf, Dale J.
supporting information; experimental part, p. 5444 - 5448 (2010/05/02)
The HIV protease inhibitor ritonavir (RTV) is also a potent inhibitor of the metabolizing enzyme cytochrome P450 3A (CYP3A) and is clinically useful in HIV therapy in its ability to enhance human plasma levels of other HIV protease inhibitors (PIs). A nov
POTENT AND HIGHLY SELECTIVE HETEROAROMATIC INHIBITORS OF NEURONAL NITRIC OXIDE SYNTHASE
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, (2008/06/13)
Peptidomimetic compounds as can inhibit neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as but not limited to stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease.
Novel 3-phenylpropane-1,2-diamine derivates as inhibitors of aminopeptidase N (APN)
Shang, Luqing,Wang, Qiang,Fang, Hao,Mu, Jiajia,Wang, Xuejian,Yuan, Yumei,Wang, Binghe,Xu, Wenfang
experimental part, p. 9984 - 9990 (2009/04/06)
Aminopeptidase N (APN) is an essential peptidase involved in the process of tumor invasion and metastasis. Here we describe a novel class of inhibitor with 3-phenylpropane-1,2-diamine as scaffold to APN. Preliminary activity evaluation with enzyme inhibition studies showed that compound 12i exhibited potent and selective inhibitory activity towards APN with the IC50 value 15.5 ± 1.2 μM.
Novel compounds that are useful for improving pharmacokinetics
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Page/Page column 39, (2008/06/13)
Novel compounds of formula 1 or a pharmaceutically acceptable salt thereof inhibit cytochrome P450 monooxygenase.
HETEROAROMATIC SELECTIVE INHIBITORS OF NEURONAL NITRIC OXIDE SYNTHASE
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Page/Page column 18, (2008/06/13)
Compounds inhibiting neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, such compounds of a formula.
MONOCYCLIC COMPOUNDS WITH FOUR BIFUNCTIONAL RESIDUES HAVING NK-2 ANTAGONIST ACTION
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, (2008/06/13)
Disclosed are monocyclic compounds containing four bifunctional residues linked together via peptide or pseudopeptide bonds of the general formula (I):having tachykinin receptor antagonist activity. In particular, compounds of formula I are shown to be ne
Synthesis of C2-symmetric (S,S)-1,4-dibenzyl-DTPA and 1,4-meso-dibenzyl-DTPA via chiral diamines
Sajiki, Hironao,Ong, Karen Y.
, p. 14507 - 14514 (2007/10/03)
Novel routes to C2-symmetric (S,S)-1,4-dibenzyl-DTPA and 1,4-meso-dibenzyl-DTPA are described. The methodology utilizes readily available starting materials.
