1699-03-2Relevant articles and documents
Dihydrodibenzothiepine: Promising hydrophobic pharmacophore in the influenza cap-dependent endonuclease inhibitor
Akiyama, Toshiyuki,Hasegawa, Yasushi,Kawai, Makoto,Miyagawa, Masayoshi,Noshi, Takeshi,Shishido, Takao,Taoda, Yoshiyuki,Tomita, Kenji,Yoshida, Ryu
, (2020/09/22)
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.
Asymmetric synthesis of carbocycles: Use of intramolecular conjugate displacement
Sreedharan, Dinesh T.,Clive, Derrick L. J.
, p. 3128 - 3144 (2013/06/04)
Intramolecular conjugate displacement (ICD), the process illustrated in eqn (1), has been applied to the Morita-Baylis-Hillman adducts formed from (5S)-5-(l-menthyloxy)-2(5H)-furanone and aldehydes that are substituted in the γ- or δ-position by geminal phenylthio groups. When the initial Morita-Baylis-Hillman alcohols are acetylated and oxidized to geminal sulfones, deprotonation causes ring closure by ICD (2.5→2.6). Hydrogenation, DIBAL-H reduction and desulfonylation releases an optically pure carbocycle. The Royal Society of Chemistry 2013.
Investigation of the solvent enclathration potentials of 5-phenyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol and related seven-membered ring alcohols
Taljaard, Benjamin,Barton, Benita,McCleland, Cedric W.
, p. 44 - 48 (2007/10/03)
Four previously reported tricyclic alcohols containing seven-membered central B-rings, 5-phenyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol, 5-phenyl-5H-dibenzo[a,d]cyclohepten-5-ol, 11-phenyl-6,11-dihydrodibenzo[b,e] oxepin-11-ol and 11-phenyl-6,11-dihydrodibenzo[b,e]thiepin-11-ol have been synthesized and their solvent enclathration (inclusion) properties investigated and compared by using 1H-NMR and differential scanning calorimetry (DSC). The presence of an oxygen or a sulphur atom, respectively, in the B-ring of the latter two compounds had a detrimental effect on the solvent enclathration properties of the host compounds as compared to those containing an ethane or ethylene bridge. This suggests that, although enclathration is highly dependent on the hydrogen bonding ability of the host, rigidity of the structure plays a crucial role in the formation and stability of these complexes.
Piperidine derivative and pharmaceutical composition containing it
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, (2008/06/13)
Piperidine derivatives of formula (I) and their pharmaceutically acceptable salts have antihypertensive action. The compounds may be included in pharmaceutical compositions for oral or parenteral administration.
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
Kurokawa,Sato,Masuda,Yoshida,Ochi,Zushi,Fujiwara,Naruto,Uno,Matsumoto
, p. 2564 - 2573 (2007/10/02)
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.
SYNTHESIS OF DOTHIEPIN AND DOXEPIN BY GRIGNARD REACTIONS IN TOLUENE
Jalander, Lars,Oksanen, Lasse,Taehtinen, Johanna
, p. 3349 - 3352 (2007/10/02)
The tricyclic antidepressant agents 11-(3-N,N-dimethylaminopropylidene)-6H,11H-dibenzo--thiepin hydrochloride (Dothiepin) and 11-(3-N,N-dimethylaminopropylidene)-6H,11H-dibenzo-oxepin hydrochloride (Doxepin) have been prepared in good yield by Grignard reactions in toluene.
