- Practical Synthesis of N-{4-[(2-Methyl-4,5-dihydroimidazo[4,5-d][1] benzazepin-6(1H)-yl)carbonyl]phenyl}biphenyl-2-carboxamide Monohydrochloride: An Arginine Vasopressin Antagonist
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A novel, reliable, and cost-effective synthetic route to N-{4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl] -phenyl}biphenyl-2-carboxamide monohydrochloride (1, YM087), a potent Arginine vasopressin antagonist, has been developed. Using moisture-controlled potassium carbonate, imidazole formation from α-bromoketone furnished imidazobenzazepine, avoiding potential oxazole-ring formation. Catalytic reduction of nitro imidazobenzazepine afforded the corresponding amine in high yields. Treatment of the imidazole-containing amine directly, with a carbonyl chloride, afforded the target amide circumventing protection of the imidazole.
- Tsunoda, Takashi,Yamazaki, Atsuki,Iwamoto, Hidenori,Sakamoto, Shuichi
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- Photochemical Fries Rearrangement of N-Phenyl-2-pyrrolidone
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Photochemical Fries rearrangement of 1-phenyl-2-pyrrolidone (1) proceeded smoothly in methanol especially in the presence of piperylene.Continous photo-irradiation of 1 successfully was carried out to raise the yield by utilizing a reaction mixture-circulation system containing of a spiral quartz cell, a pump, a uv light source and a column packed with appropriate absorbents for the Fries rearranged product (3) and pigments.
- Ohta, Shunsaku,Sano, Atsunori,Yamashita, Masayuki,Okamoto, Masao
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- Benzo [b] aza-chalcone heterocomplex as well as preparation method and application thereof
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The invention discloses a benzo [b] aza-chalcone heterocomplex as well as a preparation method and application thereof, and relates to the technical field of medicinal chemistry, the benzo [b] aza-chalcone heterocomplex is prepared by retaining a natural chalcone parent structure (1, 3-diphenyl propenone) with certain anti-tumor activity by adopting a medicine combination principle and meanwhile introducing a benzo [b] aza structure with a special structure type and electron cloud distribution to obtain the novel benzo [b] aza-chalcone heterocomplex; and pharmacological studies show that the compound can significantly inhibit the activity of human gastric cancer cells HGC-27, the activity of the compound is obviously higher than that of positive control cis-platinum, and meanwhile, the compound has low toxicity to human normal gastric mucosa cells GES-1 and is obviously lower than that of the positive control cis-platinum.
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- 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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p. 8670 - 8692
(2018/10/05)
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- Stereochemistry of N-Benzoyl-5-substituted-1-benzazepines Revisited: Synthesis of the Conformationally Biased Derivatives and Revision of the Reported Structure
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The syn (aR?,5R?) and anti (aS?,5R?) diastereomers of N-benzoyl-C5-substituted-1-benzazepines originating in the chiralities at C5 and the Ar-N(C=O) axis were first stereoselectively synthesized by biasing the conformation with a substituent at C6 and C9, respectively. Detailed examination of the stereochemistry (i.e., conformation and configuration) of these N-benzoyl-1-benzazepines by X-ray crystallographic analysis, VT NMR, and DFT calculations revealed new physicochemical aspects of these heterocycles including revision of the stereochemistry previously reported.
- Tabata, Hidetsugu,Yoneda, Tetsuya,Tasaka, Tomohiko,Ito, Shigekazu,Oshitari, Tetsuta,Takahashi, Hideyo,Natsugari, Hideaki
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p. 3136 - 3148
(2016/05/19)
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- VASOPRESSIN V1A ANTAGONISTS
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The present invention concerns compounds inter alia according to general formula 1a. Compounds according to the invention are vasopressin V 1a receptor antagonists. Pharmaceutical compositions of the compounds are useful as treatment of dysmenorrhoea.
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Page/Page column 34
(2008/06/13)
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- COMPOUNDS AND METHODS FOR TREATING DYSLIPIDEMIA
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Compounds of formula I wherein n, m, p, q, Y, R1 R2, R3, R4, R5, and R6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating artherosclerosis and its sequelae.
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Page/Page column 39
(2008/06/13)
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