Raymond F. Horvath
Aventis Pharma
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Publication
Featured researches published by Raymond F. Horvath.
Bioorganic & Medicinal Chemistry Letters | 2008
Taeyoung Yoon; Stéphane De Lombaert; Robbin Brodbeck; Michael Gulianello; Jayaraman Chandrasekhar; Raymond F. Horvath; Ping Ge; Mark T. Kershaw; James E. Krause; John H. Kehne; Diane Hoffman; Dario Doller; Kevin J. Hodgetts
The design, synthesis and structure-activity relationships of a novel series of CRF-1 receptor antagonist, the 1-aryl-4-alkylaminoisoquinolines, is described. The effects of substitution on the aromatic ring, the amino group and the isoquinoline core on CRF-1 receptor binding were investigated.
Journal of Medicinal Chemistry | 2011
Kevin J. Hodgetts; Ping Ge; Taeyoung Yoon; Stéphane De Lombaert; Robbin Brodbeck; Michael Gulianello; Andrzej Kieltyka; Raymond F. Horvath; John H. Kehne; James E. Krause; George D. Maynard; Diane Hoffman; Younglim Lee; Laurence Fung; Dario Doller
The design, synthesis, and structure-activity relationships of a novel series of pyrazines, acting as corticotropin releasing factor-1 (CRF-1) receptor antagonists, are described. Synthetic methodologies were developed to prepare a number of substituted pyrazine cores utilizing regioselective halogenation and chemoselective derivatization. Noteworthy, an efficient 5-step synthesis was developed for the lead compound 59 (NGD 98-2), which required no chromatography. Compound 59 was characterized as an orally bioavailable, brain penetrant, and highly selective CRF-1 receptor antagonist. Occupancy of rat brain CRF-1 receptors was quantified using ex vivo receptor occupancy assays, using both brain tissue homogenates as well as brain slices receptor autoradiography. Behaviorally, oral administration of 59 significantly antagonized CRF-induced locomotor activity at doses as low as 10 mg/kg and dose-dependently reduced the restraint stress-induced ACTH increases.
Bioorganic & Medicinal Chemistry Letters | 2008
Taeyoung Yoon; Stéphane De Lombaert; Robbin Brodbeck; Michael Gulianello; James E. Krause; Alan Hutchison; Raymond F. Horvath; Ping Ge; John H. Kehne; Diane Hoffman; Jayaraman Chandrasekhar; Dario Doller; Kevin J. Hodgetts
The design, synthesis and structure-activity relationship studies of a novel series of CRF-1 receptor antagonists, the 2-arylpyrimidines, are described. The effects of substitution on the aromatic ring and the pyrimidine core on CRF-1 receptor binding were investigated. A number of compounds with K(i) values below 10 nM and lipophilicity in a minimally acceptable range for a CNS drug (cLogP<5) were discovered.
Bioorganic & Medicinal Chemistry Letters | 2016
Charles-Henry Fabritius; Ullamari Pesonen; Josef Messinger; Raymond F. Horvath; Harri Salo; Michal Galezowski; Mariusz Galek; Klaudia Stefańska; Joanna Szeremeta-Spisak; Marta Olszak-Płachta; Anna Małgorzata Buda; Justyna Adamczyk; Marcin Król; Peteris Prusis; Magdalena Sieprawska-Lupa; Maciej Mikulski; Katja Kuokkanen; Hugh Chapman; Radosław Obuchowicz; Timo Korjamo; Niina Jalava; Mateusz Nowak
A series of 1-Sulfonyl-6-Piperazinyl-7-Azaindoles, showing strong antagonistic activity to 5-HT6 receptor (5-HT6R) was synthesized and characterized. The series was optimized to reduce activity on D2 receptor. Based on the selectivity against this off-target and the analysis of the ADME-tox profile, compound 1c was selected for in vivo efficacy assessment, which demonstrated procognitive effects as shown in reversal of scopolamine induced amnesia in an elevated plus maze test in mice. Compound 3, the demethylated version of compound 1c, was profiled against a panel of 106 receptors, channels and transporters, indicating only D3 receptor as a major off-target. Compound 3 has been selected for this study over compound 1c because of the higher 5-HT6R/D2R binding ratio. These results have defined a new direction for the design of our pseudo-selective 5-HT6R antagonists.
Archive | 1999
Raymond F. Horvath; James W. Darrow; George D. Maynard
Archive | 2004
Ping Ge; Raymond F. Horvath; Lu Yan Zhang; Yasuchika Yamaguchi; Bernd Kaiser; Xuechun Zhang; Suoming Zhang; He Zhao; Stanly John; Neil Moorcroft; Greg Shutske
Archive | 2004
Kevin J. Hodgetts; Stanly John; Neil Moorcroft; Greg Shutske; Bernd Kaiser; Yasuchika Yamaguchi; Ping Ge; Raymond F. Horvath
Archive | 2002
Raymond F. Horvath; Alan Hutchison
Archive | 2001
Lombaert Stephane De; Ping Ge; Raymond F. Horvath; Taeyoung Yoon
Archive | 1999
Ping Ge; Raymond F. Horvath; Stéphane De Lombaert