5176-30-7Relevant academic research and scientific papers
RESORCINOL DERIVATIVE AS HSP90 INHIBITOR
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Paragraph 0077, (2017/12/27)
The present invention relates to a compound represented by formula (I) of a resorcinol derivative as an HSP90 inhibitor or pharmaceutically accepted salts thereof. The compound in the present invention has the activity of inhibiting heat shock protein HSP90. Therefore, the compound in the present invention is used to treat proliferative diseases such as cancer and neurodegenerative diseases. The present invention further provides the compounds and preparation methods for pharmaceutical compositions comprising the compounds, a method for treating diseases, and pharmaceutical compositions comprising the compounds.
7-Azabicyclo[2.2.1]heptane as a structural motif to block mutagenicity of nitrosamines
Ohwada, Tomohiko,Ishikawa, Satoko,Mine, Yusuke,Inami, Keiko,Yanagimoto, Takahiro,Karaki, Fumika,Kabasawa, Yoji,Otani, Yuko,Mochizuki, Masataka
experimental part, p. 2726 - 2741 (2011/06/11)
Nitrosamines are potent carcinogens and toxicants in the rat and potential genotoxins in humans. They are metabolically activated by hydroxylation at an α-carbon atom with respect to the nitrosoamino group, catalyzed by cytochrome P450. However, there has been little systematic investigation of the structure-mutagenic activity relationship of N-nitrosamines. Herein, we evaluated the mutagenicity of a series of 7-azabicyclo[2.2.1]heptane N-nitrosamines and related monocyclic nitrosamines by using the Ames assay. Our results show that the N-nitrosamine functionality embedded in the bicyclic 7-azabicylo[2.2.1]heptane structure lacks mutagenicity, that is, it is inert to α-hydroxylation, which is the trigger of mutagenic events. Further, the calculated α-C-H bond dissociation energies of the bicyclic nitrosamines are larger in magnitude than those of the corresponding monocyclic nitrosamines and N-nitrosodimethylamine by as much as 20-30 kcal/mol. These results are consistent with lower α-C-H bond reactivity of the bicyclic nitrosamines. Thus, the 7-azabicyclo[2.2.1]heptane structural motif may be useful for the design of nongenotoxic nitrosamine compounds with potential biological/medicinal applications.
Transnitrosation of thiols from aliphatic N-nitrosamines: S-nitrosation and indirect generation of nitric oxide
Yanagimoto, Takahiro,Toyota, Takeshi,Matsuki, Norio,Makino, Yumi,Uchiyama, Seiichi,Ohwada, Tomohiko
, p. 736 - 737 (2007/10/03)
S-Nitrosothiols and heme nitrosyl species are nitric oxide (NO)-derived metabolites that provide an endogenous reservoir of NO and also play roles in protein S-nitrosation, that is, transnitrosation of thiols (or thiolates) in proteins, thereby regulating protein functions and signal transduction pathways. Intriguingly, endogenous N-nitrosamines are present in similar abundance to S-nitrosothiols, and though they are thought to play similar physiological roles to S-nitrosothiols, their transnitrosation reactivities and their contribution to biological events are little understood. Herein we report aliphatic N-nitroso derivatives of 7-azabicyclo[2.2.1]heptanes, which do not act as NO donors themselves, but can transnitrosate thiols. On the basis of the calculated activation energies of transnitrosation and the aorta smooth-muscle relaxation activities of these N-nitrosamines, we present a possible scenario of S-transnitrosation from aliphatic N-nitrosamines, leading to indirect generation of NO. Copyright
Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers
Li, Bryan,Berliner, Martin,Buzon, Richard,Chiu, Charles K.-F.,Colgan, Stephen T.,Kaneko, Takushi,Keene, Nandell,Kissel, William,Le, Tung,Leeman, Kyle R.,Marquez, Brian,Morris, Ronald,Newell, Lisa,Wunderwald, Silke,Witt, Michael,Weaver, John,Zhang, Zhijun,Zhang, Zhongli
, p. 9045 - 9050 (2007/10/03)
(Chemical Equation Presented) Aqueous phosphoric acid (85 wt %) is an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis of clarithromycin derivative 4, in which a tert-butyl ester is removed in the presence of cyclic carbamate, lactone, ketal, acetate ester, and epimerizable methyl ketone functionalities. The reaction preserves the stereochemical integrity of the substrates. The reactions are high yielding, and the workup is convenient.
An Evaluation of Amide Group Planarity in 7-Azabicyclo[2.2.1]heptane Amides. Low Amide Bond Rotation Barrier in Solution
Otani, Yuko,Nagae, Osamu,Naruse, Yuji,Inagaki, Satoshi,Ohno, Masashi,Yamaguchi, Kentaro,Yamamoto, Gaku,Uchiyama, Masanobu,Ohwada, Tomohiko
, p. 15191 - 15199 (2007/10/03)
Here we show that amides of bicyclic 7-azabicyclo[2.2.1]heptane are intrinsically nitrogen-pyramidal. Single-crystal X-ray diffraction structures of some relevant bicyclic amides, including the prototype N-benzoyl-7-azabicyclo[2.2.1]heptane, exhibited nitrogen-pyramidalization in the solid state. We evaluated the rotational barriers about the amide bonds of various N-benzoyl-7-azabicyclo[2.2.1]heptanes in solution. The observed reduction of the rotational barriers of the bicyclic amides, as compared with those of the monocyclic pyrrolidine amides, is consistent with a nitrogen-pyramidal structure of 7-azabicyclo[2.2.1]heptane amides in solution. A good correlation was found between the magnitudes of the rotational barrier of N-benzoyl-7-azabicyclo[2.2.1]heptanes bearing para-substituents on the benzoyl group and the Hammett's σp+ constants, and this is consistent with the similarity of the solution structures. Calculations with the density functional theory reproduced the nitrogen-pyramidal structures of these bicyclic amides as energy minima. The calculated magnitudes of electron delocalization from the nitrogen nonbonding nN orbital to the carbonyl π* orbital of the amide group evaluated by application of the bond model theory correlated well with the rotational barriers of a variety of amides, including amides of 7-azabicyclo[2.2.1]heptane. The nonplanarity of the amide nitrogen of 7-azabicyclo[2.2.1]heptanes would be derived from nitrogen-pyramidalization due to the CNC angle strain and twisting of the amide bond due to the allylic strain.
Solvolysis of N-Chloro-1,4-dihydro-1,4-iminonaphthalenes (7-Azabenzonorbornadienes); Dependence of the Rearrangement Pathway on the Configuration at Nitrogen
Durrant, Michael L.,Malpass, John R.
, p. 7063 - 7076 (2007/10/02)
N-Chloro- derivatives of the 1,4-dihydro-1,4-iminonaphthalene (7-azabenzonorbornadiene) ring system undergo silver (I)-assisted rearrangement with participation of etheno- (syn-chloro- series) or benzo- (anti-chloro- series) ?-electrons.The high barriers to inversion at nitrogen together with some control over the ratio of invertomers allow observation of a different reaction pathway for each invertomer when reactions are performed at low temperatures; approaches which allow selection of the benzo- participation route (giving 6,7-benzo-derivatives of the 1-azabicyclohept-3-ene ring system) are described.
