Dr. HERVE PORAS
PhD in 1996: Synthesis and In Vitro Antibacterial Activity of Catechol-Spiramycin Conjugates: Spiramycine Transport inside negative Gram bacteria” (Gerhard Kunesch, ICCMO, Université de Paris Sud Orsay)
Post-Doctoral fellowship 1996-1998: “Asymmetric synthesis and reactivity of polyfluorated hemiketals: synthesis of optically active polyfluorated secondary alcohols” (Tamejiro Hiyama, Sagami Chemical Research Center, Japan)
Post-Doctoral fellowship 1999-2002: “Synthesis of hypertensor, dual or triple inhibitors of Angiotensin Converting Enzyme (ACE), Endothelin Converting Enzyme (ECE) or Neprilysin (NEP)” (Bernard Roques, Laboratoire de Pharmacochimie Moléculaire et Structurale, University of Pharmaceutical Sciences – Paris V)
CMC Director and Chief Scientific Officer in 2002-2023: Preclinical and clinical development of first-in-class non opioid new painkillers, DENKIs, double enkephalinase inhibitors (Pharmaleads, Paris)
‘’Synergistic effect of combining dual enkephalinase inhibitor PL37 and sumatriptan in a preclinical model of migraine’’ Headache 2024, 64, 243-252.
‘’Efficacy of Dual ENKephalinase Inhibition in a preclinical migraine model is mediated by activation of peripheral delta opioid receptors’’ Headache 2023, 63, 621-633.
‘’The inhibition of Enkephalin Catabolism by Dual ENKephalinase Inhibitor: A novel possible therapeutic approach for opioid use disorders’’ Br. J. Pharmacol. 2023, 180, 879-893.
‘’Dual ENKephalinase Inhibitor (DENKI) PL37 as a potential novel acute and preventive treatment of Migraine’’ Brain 2022, 145, 2664-2670.
‘’Process for industrial preparation of the disodium salt of ((2S)-3-([1,1′-biphenyl]-4-yl)-2-((hydroxy((1R)-1-(((1-(isobutyryloxy)ethoxy)carbonyl)amino)ethyl)phosphoryl) methyl)propanoyl)-L-alanine WO2021/116617.
‘’N-Formylhydroxylamines as Neprilysin (NEP) inhibitors, in particular as mixed inhibitors of aminopeptidase N (APN) and Neprilysin (NEP)’’ WO2021/005294.
‘’Dual enkephalinase inhibitor (DENKI) PL265: a novel topical treatment to alleviate corneal inflammation and ocular pain’’ Pain 2019, 160, 307-321.
‘’Amino acid derivatives containing a disulfanyl group in the form of a NEP and APN inhibitor for the prevention and treatment of trigeminal nerve pain’’ WO2019/145507.
‘’Aminophosphinic derivatives for preventing and treating ocular inflammation’’ WO2018/162860.
‘’Aminophosphinic derivatives for preventing and treating eye pain’’ WO2017/093322.
‘’Substituted α-mercaptoketones, new types of specific neprilysin inhibitors” Bioorg. Med. Chem. Lett. 2017, 3883-3389.
‘’Industrial process of (5S,10S)-10-benzyl-16-methyl-11,14,18-trioxo-15,17,19-trioxa-2,7,8-trithia-12-azahenicosan-5-aminium (E)-3-carboxyacrylate salt’’ WO2017/064250.
‘’Synergistic combinations of the dual enkephalinase inhibitor PL265 given orally with various analgesic compounds acting on different targets, in a murine model of cancer-induced bone pain’’ Scand. J. Pain 2017, 14, 25-38.
‘’Preventive and alleviative effects of the dual enkephalinase inhibitor (Denki) PL265 in a murine model of neuropathic pain’’ Eur. J. Pharmacol. 2016, 788, 176-182.
‘’Modulation of Disulfide Dual Enkephalinase Inhibitors (DENKIs) Activity by a Transient N-protection for Pain Alleviation by Oral Route’’ Eur. J. Med. Chem. 2015, 102, 58-67.
‘’Long lasting oral analgesic effects of N-Protected Aminophosphinic Dual ENKephalinase Inhibitors (DENKIs) in peripherally-controlled pain’’ Pharm. Res. Per. 2015, 3, e00116.
‘’New orally active Dual ENKephalinase Inhibitors (DENKIs) for central and peripheral pain treatment’’”5763″ Med. Chem. 2014, 57, 5748-5763.
‘’Mixed inhibitors of aminopeptidase N and Neprilysin’’ WO2014/064162.
‘’Neprilysin Inhibitors’’ WO2014/064166.
‘’A sensitive fluorigenic substrate for selective in vitro and in vivo assay of leukotriene A4 hydrolase activity’’ Anal. Biochem. 2013, 441, 152-161.
‘’Comparison of fluorigenic peptide substrates PL50, SNAPtide and BoTest A/E for BoNT/A detection and quantification: exosite binding confers high assay sensitivity’’ J. Biomol. Screen. 2013, 18, 726-735.
‘’A highly sensitive fluorescent quenched substrate of the Legionella Major Secretory Protein (Msp) based on its structural analysis’’ J. Biol. Chem. 2012, 287, 20221-20230.
‘’Novel substrates the fluorescence of which is suppressed, preparation thereof, for identifying, detecting, and assaying Legionella Pneumophila’’ WO2012/010668.
‘’Agents for the molecular imaging of serine-protease in human pathologies’’ WO2012/072819.
‘’Pluripotentialities of a quenched fluorescent peptide substrate library: enzymatic detection, characterization, and isoenzymes differentiation’’ Anal. Biochem. 2011, 419, 95-105.
‘’Identification of an endothelin-converting enzyme-2-specific fluorigenic substrate and development of an in Vitro and ex Vivo enzymatic assay’’ J. Biol. Chem. 2010, 285, 34390-34400.
‘’Aminophosphinic derivatives that can be used in the treatment of pain’’ WO2010/010106.
‘’Structure of aminopeptidase N from Escherichia coli complexed with the transition-state analogue aminophosphinic inhibitor PL250’’ Acta Crystallogr., Sect. D: Biol. Crystallogr. 2009, D65, 814-822.
‘’Detection and quantification of botulinum neurotoxin type A by a novel rapid in vitro fluorimetric assay’’ Appl. Env. Microbiol. 2009, 75, 4382-4390.
‘’Novel amino acid derivatives, method for preparing same, and therapeutic use thereof’’ WO2009/138436.
‘’Inhibition of osteosarcoma-induced thermal hyperalgesia in mice by the orally active dual enkephalinase inhibitor PL37. Potentialisation by gabapentin’’ Eur. J. Pharmacol. 2008, 596, 50-55.
‘’Vasopeptidases inhibitors of ACE, NEP and ECE’’ PharmaChem 2004, 3, 41-45.
‘’In vivo properties of thiol inhibitors of the three vasopeptidases NEP, ACE and ECE are improved by introduction of a 7-azatryptophan in P’2 position’’ J. Pept. Res. 2004, 63, 99-107.
‘’N-[2-(indan-1-yl)-3-mercapto-propionylamino] derivatives of the α-aminoacids as highly potent inhibitors of the three vasopeptidases. In vitro and in vivo activities’’ Bioorg. Med. Chem. Lett. 2002, 12, 2001-2005.
‘’Towards an optimal joint recognition of the S’1 subsites of endothelin converting enzyme-1 (ECE-1), angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP)’’ J. Med. Chem. 2002, 45, 1477-1486.
‘’Amino acid derivatives and use thereof as NEP, ACE and ECE inhibitors’’ WO2001/060822.
‘’Stereospecific nucleophilic substitution of optically active 1-benzyloxy-2,2,2-trifluoroethyl tosylate with lithium tetraalkylaluminates prepared by Ti-catalyzed hydroalumination of olefins’’ Synlett 1998, 1353-1354.
‘’Nucleophilic substitution of optically active 1-Alkoxy(polyfluoro)alkyl sulfonate’’ Chem. Commun. 1998, 1259-1260.
‘’Asymmetric Synthesis of 1-Alkoxy-2,2,2-Trifluoroethanol Derivatives’’ Chem. Lett. 1998, 665-666.
‘’Synthesis and In Vitro Antibacterial Activity of Catechol-Spiramycin Conjugates’’ J. Antibiotics 1998, 51, 786-794.
‘’Easy access to some chiral 2- or 3-substitued 1-indanones and 3,4-dihydrocoumarins’’ Chemistry and Industry 1993, 206-208.
