3470-51-7Relevant academic research and scientific papers
ACYL HYDRAZONE LINKERS, METHODS AND USES THEREOF
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Paragraph 00240, (2019/07/04)
The present application is directed to compounds of Formula (I)-(VI): (I), (II), (III), (IV), (V) (VI), (VII) and (VIII), compositions comprising these compounds and their uses, for example as medicaments and/or diagnostics.
Substituted 6,7-dihydro-5H-benzo[7]annulene compounds, processes for their preparation and therapeutic uses thereof
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Page/Page column 197, (2017/08/26)
Compounds of formula (I): wherein R1 and R2 represent hydrogen or deuterium atoms; R3 represents a hydrogen atom or a —COOH, a —OH or a —OPO(OH)2 group; R4 represents a hydrogen atom or a fluorine atom; R5 represents a hydrogen atom or a —OH group; wherein at least one of R3 or R5 is different from a hydrogen atom; when R3 represents a —COOH, —OH or —OPO(OH)2 group, then R5 represents a hydrogen atom; when R5 represents a —OH group, then R3 and R4 represent hydrogen atoms; and R6 is selected from an optionally substituted phenyl, heteroaryl, cycloalkyl and heterocycloalkyl group; and the preparation and the therapeutic uses of the compounds of formula (I) as inhibitors and degraders of estrogen receptors, useful especially in the treatment of cancer.
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
Influence of the length and positioning of the antiestrogenic side chain of endoxifen and 4-hydroxytamoxifen on gene activation and growth of estrogen receptor positive cancer cells
Maximov, Philipp Y.,Fernandes, Daphne J.,McDaniel, Russell E.,Myers, Cynthia B.,Curpan, Ramona F.,Jordan, V. Craig
, p. 4569 - 4583 (2014/07/07)
Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains. Pharmacologic properties were documented in the MCF-7 cell line, and prolactin synthesis was assessed in GH3 rat pituitary tumor cells. The FR Z-isomers of 4OHT and endoxifen were equivalent to 4OHT and endoxifen. Other test compounds used possessed partial estrogenic activity. The E-isomers of FR 4OHT and endoxifen had no estrogenic activity at therapeutic serum concentrations. None of the newly synthesized compounds were able to down-regulate ER levels. Molecular modeling demonstrated that some compounds would each create a best fit with a novel agonist conformation of the ER. The results demonstrate modulation by the ER complex of cell replication or gene transcription in cancer.
A photo-favorskii ring contraction reaction: The effect of ring size
Kammath, Viju Balachandran,?olomek, Tomá?,Ngoy, Bokolombe Pitchou,Heger, Dominik,Klán, Petr,Rubina, Marina,Givens, Richard S.
, p. 1718 - 1729 (2013/03/29)
The effect of ring size on the photo-Favorskii induced ring-contraction reaction of the hydroxybenzocycloalkanonyl acetate and mesylate esters (7a-d, 8a-c) has provided new insight into the mechanism of the rearrangement. By monotonically decreasing the ring size in these cyclic derivatives, the increasing ring strain imposed on the formation of the elusive bicyclic spirocyclopropanone 20 results in a divergence away from rearrangement and toward solvolysis. Cycloalkanones of seven or eight carbons undergo a highly efficient photo-Favorskii rearrangement with ring contraction paralleling the photochemistry of p-hydroxyphenacyl esters. In contrast, the five-carbon ring does not rearrange but is diverted to the photosolvolysis channel avoiding the increased strain energy that would accompany the formation of the spirobicyclic ketone, the "Favorskii intermediate 20". The six-carbon analogue demonstrates the bifurcation in reaction channels, yielding a solvent-sensitive mixture of both. Employing a combination of time-resolved absorption measurements, quantum yield determinations, isotopic labeling, and solvent variation studies coupled with theoretical treatment, a more comprehensive mechanistic description of the rearrangement has emerged.
Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that Act as G protein-coupled receptor 40/free fatty acid receptor 1 agonists
Negoro, Nobuyuki,Sasaki, Shinobu,Ito, Masahiro,Kitamura, Shuji,Tsujihata, Yoshiyuki,Ito, Ryo,Suzuki, Masami,Takeuchi, Koji,Suzuki, Nobuhiro,Miyazaki, Junichi,Santou, Takashi,Odani, Tomoyuki,Kanzaki, Naoyuki,Funami, Miyuki,Tanaka, Toshimasa,Yasuma, Tsuneo,Momose, Yu
scheme or table, p. 1538 - 1552 (2012/04/10)
The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2′,6′-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl} propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to β-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-yl]methoxy} -2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.
Efficient Method for Preparing Functionalized Benzosuberenes
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Page/Page column 17, (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.
A convenient new method for 2-hydroxy-6,7,8,9-tetrahydro-5H- benzocyclohepten-5-one
Nagarapu, Lingaiah,Srinivasulu
, p. 479 - 482 (2007/10/03)
A novel approach has been developed for the synthesis of 2-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-one is reported using 4-carboxybutyl triphenyl phosphonium bromide (Wittig salt) in excellent yield.
