- LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism
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Oxytocin (OT) and its receptor (OT-R) are implicated in the etiology of autism spectrum disorders (ASD), and OT-R is a potential target for therapeutic intervention. Very few nonpeptide oxytocin agonists have currently been reported. Their molecular and in vivo pharmacology remain to be clarified, and none of them has been shown to be efficient in improving social interaction in animal models relevant to ASD. In an attempt to rationalize the design of centrally active nonpeptide full agonists, we studied in a systematic way the structural determinants of the affinity and efficacy of representative ligands of the V1a and V2 vasopressin receptor subtypes (V1a-R and V2-R) and of the oxytocin receptor. Our results confirm the subtlety of the structure-affinity and structure-efficacy relationships around vasopressin/oxytocin receptor ligands and lead however to the first nonpeptide OT receptor agonist active in a mouse model of ASD after peripheral ip administration.
- Frantz, Marie-Céline,Pellissier, Lucie P.,Pflimlin, Elsa,Loison, Stéphanie,Gandiá, Jorge,Marsol, Claire,Durroux, Thierry,Mouillac, Bernard,Becker, Jér?me A. J.,Le Merrer, Julie,Valencia, Christel,Villa, Pascal,Bonnet, Dominique,Hibert, Marcel
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supporting information
p. 8670 - 8692
(2018/10/05)
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- KDM1A INHIBITORS FOR THE TREATMENT OF DISEASE
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Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.
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Paragraph 0553; 0555
(2016/09/26)
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- ANTI-HCMV COMPOSITIONS AND METHODS
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Novel compounds useful for treating and/or preventing HCMV infections are provided.
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Page/Page column 44; 45
(2016/06/06)
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- Benzoimidazole derivatives and pharmaceutical composition comprising the same
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Disclosed herein are novel benzoimidazole derivatives functioning as antagonists to vanilloid receptor-1, and a pharmaceutical composition comprising the same. They are useful in preventing or treating pain, acute pain, chronic pain, neuropathic pain, pos
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Page/Page column 16; 36
(2015/12/17)
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- PYRROLIDINE OR THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERSAS AS AGONISTS OF G- PROTEIN COUPLED RECEPTOR 43 (GPR43)
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The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases.
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Page/Page column 204
(2011/07/07)
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- Pyrrolobenzodiazepine pyridine carboxamides and derivatives as follicle-stimulating hormone receptor antagonists
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This invention provides pyrrolobenzodiazepine pyridine carboxamides selected from those of Formula (1), which act as follicle stimulating hormone receptor antagonists. The invention also provides pharmaceutical compositions and methods of treatment utilizing the compounds of Formulae (1) and (2).
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Page/Page column 51
(2010/11/25)
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- Biarylcarboxybenzamide derivatives as potent vanilloid receptor (VR1) antagonistic ligands
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Seventeen biarylcarboxybenzamide derivatives were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor (VR1) in rat DRG neurons. The replacement of the piperazine moiety of the lead compound 1 with phenyl ring showed quite enhanced antagonistic activity. Among the prepared derivatives, N-(4-tert-butylphenyl)-4-pyridine-2-yl-benzamide (2, IC 50 = 31 nM) and N-(4-tert-butylphenyl)-4-(3-methylpyridine-2-yl) benzamide (3g, IC50 = 31 nM), showed 5-fold higher antagonistic activity than 1 in 45Ca2+-influx assay.
- Park, Hyeung-Geun,Choi, Ji-Yeon,Kim, Mi-Hyun,Choi, Sea-Hoon,Park, Mi-Kyung,Lee, Jihye,Suh, Young-Ger,Cho, Hawon,Oh, Uhtaek,Kim, Hee-Doo,Joo, Yung Hyup,Shin, Song Seok,Kim, Jin Kwan,Jeong, Yeon Su,Koh, Hyun-Ju,Park, Young-Ho,Jew, Sang-Sup
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p. 631 - 634
(2007/10/03)
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- A convenient synthesis of heteroaryl benzoic acids via Suzuki reaction
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An one step approach to heteroaryl benzoic acids from readily accessible heteroaryl halides and carboxybenzene boronic acids is described. The Suzuki coupling is carried out in the presence of Pd(PPh3)4 and sodium carbonate in aqueous acetonitrile. The scope and limitations of the reaction are discussed.
- Gong, Yong,Pauls, Henry W.
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p. 829 - 831
(2007/10/03)
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