404-24-0Relevant articles and documents
Water catalyzed hydrolysis of p-nitrotrifluoroacetanilide and trifluoroacetanilide. Carbonyl 18O-exchange does not accompany the water reaction
Slebocka-Tilk,Rescorla, Christopher G.,Shirin, Salma,Bennet, Andrew J.,Brown
, p. 10969 - 10975 (1997)
The water catalyzed hydrolyses of p-nitrotrifluoroacetanilide (3) and trifluoroacetanilide (8) were studied at various pH's and temperatures. The activation parameters for the water reactions of 3 and 8 are: ΔH = 14.4 ± 0.6 and 11.7 ± 0.3 kcal/mol and ΔS = -36.1 ± 1.8 and -52.3 ± 0.7 calmol·K, respectively. These are consistent with reactions that involve considerable restriction of degrees of freedom of the solvent/substrate in the transition state. A proton inventory analysis of the rate constants for hydrolysis of 3 in media of different mole fraction D2O indicates the process involves two or more protons in flight or undergoing loosening of their bonding in the transition state. 18O-Labeled amides were subjected to the hydrolytic conditions for various times up to 3 half-times of hydrolysis and recovered. Mass analysis showed that the 180 content in the recovered amide did not change during the course of the reaction. All the data support a process where the rate-limiting step for the water reaction involves a concerted or nearly concerted formation of a diol which undergoes subsequent C-N cleavage in preference to OH expulsion.
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McBee,Burton
, p. 3902 (1952)
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Rochat,W.V.,Gard,G.L.
, p. 4173 - 4176 (1969)
Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy
Zhao, Chenxi,Tang, Chu,Li, Changhao,Ning, Wentao,Hu, Zhiye,Xin, Lilan,Zhou, Hai-Bing,Huang, Jian
, (2021/05/10)
Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.
Oxygen bridge bicyclo - [2.2.1] - heptene compounds containing different covalent bullet structures, and preparation and application thereof
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Paragraph 0139-0141, (2021/11/03)
The invention discloses an oxygen bridge bicyclo - [2.2.1] - heptene compound containing different covalent popping structures as well as preparation and application thereof, and belongs to the technical field of targeted drugs. As shown in general formula (I) or general formula (II), furan derivatives and vinylsulfonamide derivatives or vinylsulfonate derivatives containing different covalent popping heads are prepared by reacting Diels-Alder to obtain a compound of the present invention. The compound can be used for preparing anti-breast cancer drugs. A medicament for the degradation of estrogen receptors, a medicament for a mutant estrogen receptor. Compared with the existing anti-breast cancer drug tamoxifen, MCF-7 cells have stronger inhibitory activity and have the ability to down-regulate the estrogen receptor level, and the activity shown for the mutant estrogen receptor is 4 - times of 5-10 hydroxytamoxifen.
