- 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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- CYCLOALKANE DERIVATIVE
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PROBLEM TO BE SOLVED: To provide a novel cycloalkane derivative having a somatostatin receptor subtype 4 selective agonist activity useful as a therapeutic and/or preventive agent for improving symptoms of Alzheimer disease. SOLUTION: There is provided a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof. (I), where R1 and R2 are the same or different and each represent C1-4 alkyl which may be substituted or the like, n represent an integer of 1 to 3, R3 represents C1-4 alkyl which may be substituted, a hydrogen atom or the like, R4 represents C1-4 alkyl which may be substituted or the like, R5a and R5b are the same or different and each represent C6-14 aryl which may be substituted, C1-14 alkyl which may be substituted, C1-3 alkoxy which may be substituted or the like and A represents C6-14 aryl which may be substituted or 5 to 11-membered heteroaryl which may be substituted. COPYRIGHT: (C)2015,JPO&INPIT
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Paragraph 0115-0117
(2018/09/27)
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- Microwave-accelerated fluorodenitrations and nitrodehalogenations: expeditious routes to labeled PET ligands and fluoropharmaceuticals
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Methods for the expeditious fluorination of arenes have been investigated, using readily available fluoride sources. An optimized procedure for microwave-accelerated fluorodenitration has been developed, giving good to excellent yields in less than 10 min, rendering it practical for use in the preparation of F18 labeled ligands for PET imaging. Application of the method in the synthesis of CNS agents is demonstrated, and a practical method for the preparation of substrates is also presented.
- LaBeaume, Paul,Placzek, Michael,Daniels, Mathew,Kendrick, Ian,Ng, Patrick,McNeel, Melissa,Afroze, Roushan,Alexander, Abigail,Thomas, Rhiannon,Kallmerten, Amy E.,Jones, Graham B.
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experimental part
p. 1906 - 1909
(2010/09/07)
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- PYRIDAZINONE DERIVATIVES CYTOKINES INHIBITORS
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A pyridazinone derivative shown by the following formula (I): wherein; which is useful as a medicament for cytokines mediated diseases.
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Page/Page column 50
(2010/10/20)
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- Selective fluorodenitration of chloronitroaromatics
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Nucleophilic fluorination of chloronitrobenzenes shows a strong bias for fluorodenitration rather than halogen exchange.
- Beaumont, Andrew J.,Clark, James H.,Boechat, Nubia A.
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- Tetrahydrophthalimide compounds, as post-emergence herbicides for use in soybean fields
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A tetrahydrophthalimide compound of the formula: STR1 wherein R is methyl or n-pentyl, which is useful as a post emergent herbicide for a soybean field.
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- N-(2-Fluoro-4-halo-5-substituted phenyl) hydantoins
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A composition comprising an N-(2-fluoro-4-halo-5-substituted phenyl) hydantoin of the formula: STR1 wherein X is a chlorine atom or a bromine atom and R1 and R2 are, same or different, each a C1 -C4 alkyl group, a cyclopropyl group, a C3 -C4 alkenyl group or a C3 -C4 alkynyl group and an inert carrier, which is useful as a herbicide.
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- Tetrahydrophthalimides, and their production and use
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A compound of the formula: STR1 wherein X is a chlorine atom or a bromine atom, which is useful as a herbicide.
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- 2-(2-Fluoro-4-halo-5-substituted phenyl) hydantoins and use
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A herbicidal composition which comprises as an active ingredient a compound of the formula: STR1 wherein X is a chlorine atom or a bromine atom, Y is --CH2 --, --S-- or --SO2 -- and R is a C1 -C4 alkyl group, an allyl group or a propargyl group, and an inert carrier.
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- 4-(2-Fluoro-4-halo-5-substituted phenyl)urazols, and their production and use
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A condensed phenylurazol of the formula: STR1 wherein X is a chlorine atom or a bromine atom, Y and Z are each an oxygen atom or a sulfur atom and R is a C1 -C3 alkyl group, an allyl group or a propargyl group and n is an integer of 4 or 5, which is useful as a herbicide.
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