54130-94-8Relevant academic research and scientific papers
Structural interrogation of benzosuberene-based inhibitors of tubulin polymerization
Herdman, Christine A.,Devkota, Laxman,Lin, Chen-Ming,Niu, Haichan,Strecker, Tracy E.,Lopez, Ramona,Liu, Li,George, Clinton S.,Tanpure, Rajendra P.,Hamel, Ernest,Chaplin, David J.,Mason, Ralph P.,Trawick, Mary Lynn,Pinney, Kevin G.
, p. 7497 - 7520 (2015/12/18)
The discovery of 3-methoxy-9-(3′,4′,5′-trimethoxyphenyl)-6,7-dihydro-5H-benzo[7]annulen-4-ol (a benzosuberene-based analogue referred to as KGP18) was originally inspired by the natural products colchicine and combretastatin A-4 (CA4). The relative struct
Synthesis of structurally diverse benzosuberene analogues and their biological evaluation as anti-cancer agents
Tanpure, Rajendra P.,George, Clinton S.,Strecker, Tracy E.,Devkota, Laxman,Tidmore, Justin K.,Lin, Chen-Ming,Herdman, Christine A.,Macdonough, Matthew T.,Sriram, Madhavi,Chaplin, David J.,Trawick, Mary Lynn,Pinney, Kevin G.
, p. 8019 - 8032 (2014/01/06)
Diversely functionalized, fused aryl-alkyl ring systems hold a prominent position as well-established molecular frameworks for a variety of anti-cancer agents. The benzosuberene (6,7 fused, also referred to as dihydro-5H-benzo[7] annulene and benzocycloheptene) ring system has emerged as a valuable molecular core component for the development of inhibitors of tubulin assembly, which function as antiproliferative anti-cancer agents and, in certain cases, as vascular disrupting agents (VDAs). Both a phenolic-based analogue (known as KGP18, compound 39) and its corresponding amine-based congener (referred to as KGP156, compound 45), which demonstrate strong inhibition of tubulin assembly (low micromolar range) and potent cytotoxicity (picomolar range for KGP18 and nanomolar range for KGP156) are noteworthy examples of such benzosuberene-based compounds. In order to extend the structure-activity relationship (SAR) knowledge base related to benzosuberene anti-cancer agents, a series of eleven analogues (including KGP18) were prepared in which the methoxylation pattern on the pendant aryl ring as well as functional group incorporation on the fused aryl ring were varied. The synthetic approach to these compounds featured a sequential Wittig olefination, reduction, Eaton's reagent-mediated cyclization strategy to achieve the core benzosuberone intermediate, and represented a higher-yielding synthesis of KGP18 (which we prepared previously through a ring-expansion strategy). Incorporation of a fluorine or chlorine atom at the 1-position of the fused aryl ring or replacement of one of the methoxy groups with hydrogen (on the pendant aryl ring of KGP18) led to benzosuberene analogues that were both strongly inhibitory against tubulin assembly (IC50 approximately 1.0 μM) and strongly cytotoxic against selected human cancer cell lines (for example, GI50 = 5.47 nM against NCI-H460 cells with fluoro-benzosuberene analogue 37). A water-soluble phosphate prodrug salt of KGP18 (referred to as KGP265, compound 44) and a water-soluble serinamide salt (compound 48) of KGP156 were also synthesized and evaluated in this study.
Efficient Method for Preparing Functionalized Benzosuberenes
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Page/Page column 10, (2012/06/01)
The disclosed process can efficiently synthesize functionalized benzosuberenes. The process provides an improved method of production of benzosuberene and compounds containing a benzosuberene moiety, which is characterized by a ring closing methodology comprising reaction of a 5-phenylpentanoic acid with Eaton's reagent to form the benzosuberone. The process, optionally, further includes steps for adding a functional group at the ketone position.
On the conformation of 8-membered ring heterocycles - Dynamic and static conformational analysis of acylated hexahydrobenzazocines
Hassner, Alfred,Amit, Boaz,Marks, Vered,Gottlieb, Hugo E.
, p. 1256 - 1261 (2007/10/03)
A high-field NMR analysis of several acylated hexahydrobenzazocines indicates that, surprisingly, ring methylene groups are typically diastereotopic at room temperature, as the barriers for the process of enantiomerization of the eight - membered ring are
Meldrum's acids as acylating agents in the catalytic intramolecular Friedel-Crafts reaction
Fillion, Eric,Fishlock, Dan,Wilsily, Ashraf,Goll, Julie M.
, p. 1316 - 1327 (2007/10/03)
(Chemical Equation Presented) The intramolecular Friedel-Crafts acylation of aromatics with Meldrum's acid derivatives catalyzed by metal trifluoromethanesulfonates is reported. Meldrum's acids are easily prepared, functionalized, handled, and purified. The synthesis of polysubstituted 1-indanones from benzyl Meldrum's acids was investigated thoroughly, and it was shown that a variety of catalysts were effective, while accommodating a diversity of functional groups under mild conditions. The scope, limitations, and functional group tolerance (terminal alkene and alkyne, ketal, dialkyl ether, dialkyl thioether, aryl methyl ether, aryl TIPS and TBDPS ethers, nitrile- and nitro-substituted aryls, alkyl and aryl halides) for a variety of 5-benzyl (enolizable Meldrum's acids) and 5-benzyl-5-substituted Meldrum's acids (quaternized Meldrum's acids), forming 1-indanones and 2-substituted-1- indanones, respectively, are delineated. This method was further applied to the synthesis of 1-tetralones, 1-benzosuberones, and the potent acetylcholinesterase inhibitor donepezil. Rate of cyclization as a function of ring size was established for various benzocyclic ketones via competition experiments: 1-tetralones form faster than both 1-indanones and 1-benzosuberones, and 1-benzosuberones cyclize faster than 1-indanones.
Catecholamines in Rigid Framework: Synthesis and Pharmacological Evaluation of cis- and trans-6-Amino-1,2-dihydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ols
Kumar, Ashok,Singh, Rajeshwar,Khanna, J. M.,Anand, Nitya,Srimal, R. C.
, p. 880 - 884 (2007/10/02)
6-Amino-1,2-dihydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ols (cis-1 and trans-2), incorporating the α-rotameric form of norepinephrine in the trans-extended conformation have been synthesized and evaluated for their biological activity. trans-6-Amino-1,2-dihydroxy-6,7,8,9-tetrahydro-5H-benzocylohepten-5-ol (2) is found to possess marked β2-stimulant activity.
