- Pd(II)-Catalyzed [4 + 2] Heterocyclization Sequence for Polyheterocycle Generation
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A new Pd(II)-catalyzed cascade sequence for the formation of polyheterocycles, from simple starting materials, is reported. The sequence is applicable to both indole and pyrrole substrates, and a range of substituents are tolerated. The reaction is thought to proceed by a Pd(II)-catalyzed C-H activated Heck reaction followed by a second Pd(II)-catalyzed aza-Wacker reaction with two Cu(II)-mediated Pd(0) turnovers per sequence. The sequence can be considered a formal [4 + 2] heterocyclization.
- Glaisyer, Elizabeth L.,Watt, Michael S.,Booker-Milburn, Kevin I.
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supporting information
p. 5877 - 5880
(2018/09/25)
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- [(Indole -3 - yl) pyrimidine -2 - yl] amino haloalkylpropanamide -2 - enamide derivatives and salts, preparation method, application
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The invention provides a [(indole-3-yl)pyrimidine-2-yl]aminophenylpropyl-2-eneamide derivative and its salt, a preparation method of the derivative, and application of the derivative and the salt. The [(indole-3-yl)pyrimidine-2-yl]aminophenylpropyl-2-eneamide derivative has a structure shown in the formula I below. Deuterium-carbon bonds in the derivative enable the derivative to decompose slowly in a human body, a medicament of the derivative has a longer half-life period and a higher concentration in blood, the dosage of the medicament is finally reduced, and toxic and side effects of the medicament are decreased. Experiments show that compared with AZD 9291 mesylates, AZD 929-D9 mesylate of the deuterium-substituted derivative has Cmax which is 1.32 times as high as that of AZD 9291, exposed dose 1.41 times as high as that of AZD 9291, and elimination half-life 1.31 times as long as that of AZD 9291.
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Paragraph 0034; 0117; 0118; 0128; 0129
(2018/08/03)
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- Synthesis and biological evaluation of santacruzamate A analogues for anti-proliferative and immunomodulatory activity
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Santacruzamate A (SCA) is a natural product isolated from a Panamanian marine cyanobacterium, previously reported to have potent and selective histone deacetylase (HDAC) activity. To optimize the enzymatic and cellular activity, 40 SCA analogues were synthesized in a systematic exploration of the zinc-binding group (ZBG), cap terminus, and linker region. Two cap group analogues inhibited proliferation of MCF-7 breast cancer cells, with analogous increased degranulation of cytotoxic T cells (CTLs), while one cap group analogue reduced CTL degranulation, indicative of suppression of the immune response. Additional testing of these analogues resulted in reevaluation of the previously reported SCA mechanism of action. These analogues and the resulting structure–activity relationships will be of interest for future studies on cell proliferation and immune modulation.
- Gromek, Samantha M.,deMayo, James A.,Maxwell, Andrew T.,West, Ashley M.,Pavlik, Christopher M.,Zhao, Ziyan,Li, Jin,Wiemer, Andrew J.,Zweifach, Adam,Balunas, Marcy J.
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supporting information
p. 5183 - 5196
(2016/10/24)
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- SANTACRUZAMATE A COMPOSITIONS AND ANALOGS AND METHODS OF USE
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The compositions and methods described herein relate generally to Santacruzamate A compositions and analogs, which, among other features, are useful as histone deacetylase (HDAC) inhibitors.
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Page/Page column 63
(2014/02/16)
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- Flash vacuum pyrolysis of stabilised phosphorus ylides. Part 17. Preparation of aliphatic amino acid derived γ-alkoxycarbonyl-amino-β-oxo ylides and pyrolysis to give α,β-acetylenic γ-amino acid and GABA analogues
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A series of eleven α-aminoacyl stabilised phosphorus ylides 9-19 have been prepared by condensation of N-alkoxycarbonyl protected amino acids with Ph3P = CHCO2Et using a carbodiimide peptide coupling reagent. Upon flash vacuum pyrolysis at 600 °C, these undergo extrusion of Ph3PO to give the corresponding α,β-acetylenic γ-amino esters 21-29, 33 and 34 in moderate yield. In two cases the terminal alkynes 30 and 31 are also formed. The β-aminoacyl ylide 20 from β-alanine similarly gives the α,β-acetylenic δ-amino ester 35 upon pyrolysis. Regioselective addition of HBr to the triple bond of one acetylenic ester 25 was observed giving a mixture of E and Z α-bromoacrylates 36. Hydrogenation of the N-Cbz acetylenic esters 21-23 and 33 results in N-deprotection and hydrogenation of the triple bond to afford the chiral GABA analogues 37-40 in 70 ->95% ee as determined by 19F NMR of their Mosher amides. Fully assigned 13C NMR spectra of all the ylides and acetylenic ester derivatives are presented.
- Aitken, R. Alan,Karodia, Nazira,Massil, Tracy,Young, Robert J.
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p. 533 - 541
(2007/10/03)
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