- Pyridazone derivative and its uses
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The present invention belongs to the pharmaceutical field, specifically relates to a pyridazone derivative and its uses, compounds thereof and pharmaceutically acceptable salts, solvates including hydrates, polycrystallines, prodrugs, co-crystallines, tau
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Paragraph 0163
(2022/01/12)
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- Dihydrodibenzothiepine: Promising hydrophobic pharmacophore in the influenza cap-dependent endonuclease inhibitor
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This work describes a set of discovery research studies of an influenza cap-dependent endonuclease (CEN) inhibitor with a carbamoyl pyridone bicycle (CAB) scaffold. Using influenza CEN inhibitory activity, antiviral activity and pharmacokinetic (PK) parameters as indices, structure activity relationships (SAR) studies were performed at the N-1 and N-3 positions on the CAB scaffold, which is a unique template to bind two metals. The hydrophobic substituent at the N-1 position is extremely important for CEN inhibitory activity and antiviral activity, and dihydrodibenzothiepine is the most promising pharmacophore. The compound (S)-13i showed potent virus titer reduction over oseltamivir phosphate in an in vivo mouse model. The CAB compound described herein served as the lead compound of baloxavir marboxil with a tricyclic scaffold, which was approved in Japan and the USA in 2018.
- Akiyama, Toshiyuki,Hasegawa, Yasushi,Kawai, Makoto,Miyagawa, Masayoshi,Noshi, Takeshi,Shishido, Takao,Taoda, Yoshiyuki,Tomita, Kenji,Yoshida, Ryu
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- Piperazinyl-substituted pyridylalkane, alkene and alkine carboxamides
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The invention relates to new piperazinyl-substituted pyridylalkane, alkene, and alkine acid amides substituted with saturated or one or several-fold unsaturated hydrocarbon residue in the carboxylic acid group according to the general formula (I) as well as methods for the production of these compounds, medicaments containing these and their production as well as their therapeutic use, especially as cytostatic agents and immunosuppressive agents, for example in the treatment or prevention of various types of tumors and control of immune reactions such as autoimmune diseases.
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Page/Page column 167
(2010/02/11)
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- Reinvestigatioan of base-induced skeletal conversion via a spirocyctic intermediate of dibenzodithiocinium derivatives and a computational study using the HF/6-31G* basis set
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Treatment of 6-methyl-12-oxo-5H,7H-dibenzo[b,g][1,5]dithiocinium salt (1a) with methanolic KOH afforded a mixture of dibenzothiepin derivative 5 in 66% yield. The rearrangement was explained in terms of usual [2,3]-sigmatropic shift via a spirocyclic inte
- Okada, Keiji,Tanaka, Masato
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p. 2704 - 2711
(2007/10/03)
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- Synthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders
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A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e]oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3-phenyl-2-prop enyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.
- Kurokawa,Sato,Masuda,Yoshida,Ochi,Zushi,Fujiwara,Naruto,Uno,Matsumoto
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p. 2564 - 2573
(2007/10/02)
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- POTENTIAL ANTIDEPRESSANTS. SYNTHESIS OF 6,11-DIHYDRODIBENZOTHIEPIN-11-YL (DIMETHYLAMINOMETHYL)PHENYL ETHERS, SULFIDES, AMINES AND SOME RELATED COMPOUNDS
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Reactions of 11-chloro-6,11-dihydrodibenzothiepin and its 2-bromo derivative with the isomeric (dimethylaminomethyl)phenols, (dimethylaminomethyl)thiophenols, and (dimethylaminomethyl)anilines in toluene afforded the title compounds IIIb,c, Va, VIIIa,b,c, and Xa,b,c.Reactions of 11-chloro-6,11-dihydrodibenzothiepin and its 2-chloro and 2-methyl derivatives with N,N-dimethyl-2-(4-aminophenoxy)ethylamine and N,N-dimethyl-3-(4-aminophenoxy)propylamine by heating in dimethylformamide in the presence of sodium carbonate gave the diamino ethers XI-XIV.Thecompounds showed only indications of the antidepressant agents profile and some antimicrobial effects in vitro.
- Sindelar, Karel,Valenta, Vladimir,Holubek, Jiri,Matousova, Oluse,Protiva, Miroslav
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p. 282 - 295
(2007/10/02)
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- POTENTIAL ANTIHISTAMINE AGENTS: 4-(6,11-DIHYDRODIBENZOTHIEPIN-11-YLIDENE)-1-METHYLTETRAHYDROTHIOPYRANIUM IODIDE AND SIMILAR SULFONIUM SALTS DERIVED FROM RELATED TRICYCLIC SYSTEMS
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Thioxanthone, 10,11-dihydrodibenzocyclohepten-5-one, dibenzothiepin-11(6H)-one, its 2-methyl derivative, and thieno-2-benzothiepin-4(9H)-one were reacted with 4-tetrahydrothiopyranylmagnesium bromide and the obtained tertiary alcohols IVabc, VIc, and XIX were dehydrated to the olefinic sulfides IXabc, Xc, and XXI.Addition of methyl iodide afforded the title compounds XIabc, XIIc, and XXII.The Grignard reactions were accompanied by the 1,6-addition giving the ketones XVI-XVIII as by-products.The reductive properties of tetrahydrothiopyranylmagnesium bromide were most striking in the case of reaction with 2-chlorothioxanthone; the isolation of thioxanthene and thioxanthone showed that nuclear dehalogenation took also place.Reactions of 11-chloro-6,11-dihydrodibenzothiepin and benzhydryl chloride with tetrahydrothiopyran-4-ol gave the sulfides XXV and XXVIII; whereas the latter reacted with methyl iodide under the formation of sulfonium salt XXIX, the former was cleaved and gave 4-hydroxyl-1-methyltetrahydrothiopyranium iodide (XXVI).The sulfonium salts are free of the central effects but their antihistamine activity is rather low.
- Polivka, Zdenek,Holubek, Jiri,Budesinsky, Milos,Matousova, Oluse,Svatek, Emil,et al.
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p. 2758 - 2774
(2007/10/02)
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- HETEROCYCLIC ETHERS DERIVED FROM 6,11-DIHYDRODIBENZOTHIEPIN-11-OLS AND 4,9-DIHYDROTHIENO-2-BENZOTHIEPIN-4-OL; A NEW SERIES OF POTENTIAL ANTIDEPRESSANTS AND ANTIHISTAMINE AGENTS
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Reactions of 11-chloro-6,11-dihydrodibenzothiepin and methanesulfonates of 6,11-dihydrodibenzothiepin-11-ol (I), its 2-methyl derivative II and 4,9-dihydrothieno-2-benzothiepin-4-ol (III) with 1-methylpiperidin-4-ol, 1-methylperhydroazepin-4-ol (XIX), and tropine gave the ethers V-X.Their methanesulfonates were pharmacologically tested and showed antireserpine, anticataleptic, and antihistamine activities of various degree.The most active compounds were the ethers V and VI.
- Polivka, Zdenek,Metys, Jan,Protiva, Miroslav
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p. 2034 - 2049
(2007/10/02)
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- BASE INDUCED SKELETAL REARRANGEMENTS VIA SPIROCYCLIC IPSO INTERMEDIATES IN DIBENZODITHIOCINIUM SALTS
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Treatment of 6-methyl-12-oxo-5H,7H-dibenzo-dithiocinium salt (1a) with methanolic KOH afforded the ring contracted product (2a), i. e., thiepin derivatives, trans-2a (44percent) and cis-2a (19percent).However, the corresponding deoxodithiocinium salt (1b) gave an unexpected isomer (2b) with the same thiepin skeleton.These are explained by tandem sigmatropy.
- Ohkata, Katsuo,Okada, Keiji,Maruyama, Kohji,Akiba, Kin-ya
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p. 3257 - 3260
(2007/10/02)
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- N,N-diethyl-N'-{dibenzo[b,e]thiepin-11(6H)-ylidene}-1,3-propanediamine and derivatives thereof
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Dibenzo[b,e]thiepin derivatives of the formula SPC1 Wherein X is sulfur or sulfonyl and R is hydrogen or methyl, are described. The compounds of formula I are useful as diuretic agents.
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