- Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp3)?H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates
-
A novel mild, visible-light-induced palladium-catalyzed hydrogen atom translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been developed. This protocol involves a 1,5-HAT process of previously unknown hybrid vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and heterocyclic structures.
- Ratushnyy, Maxim,Parasram, Marvin,Wang, Yang,Gevorgyan, Vladimir
-
supporting information
p. 2712 - 2715
(2018/03/02)
-
- Novel small molecule compounds, preparation method thereof and method for treating/preventing HIV-1 infected aids by using compound
-
The invention provides novel small molecule compounds inhibiting HIV, especially HIV-1 virus infection, a preparation method thereof and a method for inhibiting HIV, especially HIV-1 virus infection, to treat/prevent aids and relevant diseases by using th
- -
-
Paragraph 0051
(2017/09/26)
-
- Containing difluoro methylene key bridge of the liquid crystal compound and its preparation method and composition
-
The invention discloses a liquid crystal compound containing difluoro-methylene key bridge, a preparation method of the liquid crystal compound containing difluoro-methylene key bridge and a composition containing the liquid crystal compound. The liquid c
- -
-
Paragraph 0157; 0158; 0159
(2016/10/07)
-
- Using the same hydroxamic acid derivative and HDAC8 inhibitor (by machine translation)
-
Disclosed are: a compound which is capable of inhibiting the function of HDAC8; and an HDAC8 inhibitor. Specifically disclosed is a hydroxamic acid derivative which is characterized by being composed of a compound represented by general formula (1) (wherein X represents an aromatic substituent or an optionally substituted 3-8 membered ring, and n represents an integer of 0-20), or a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof.
- -
-
Paragraph 0065; 0066
(2016/10/09)
-
- Indole derivatives and pharmaceutical composition comprising the same for treating or preventing disease related to RAGE
-
A novel indole-based derivative acceptable salt, and manufacturing method thereof including RAGE associated pharmaceutical composition for the prevention or the treatment of disorders the disclosure. Herein a derivative indole-based according to by antagonism in RAGE, nerve cells with the Amyloid-beta peptide loses purpose: a method of fabricating a apparatus move into brain, Alzheimer's disease associated RAGE disease, cerebrovascular dementia, dementia due to damage bean curd, multi blockade dementia, Alzheimer's disease or the like dementia alcoholic or mixed dementia multi blockade and including dementia, pick (pick) bottle, a smartcrew [...] -Jakob (Creutzfeldt-jakob) bottle, that thyroid gland symptoms , bean curd a blade Parkinson (Parkinson) bottle, Huntington's disease (Huntington) which is useful in preventing or treating, can be used.
- -
-
Paragraph 0519-0524
(2021/10/25)
-
- ITRACONAZOLE ANALOGS AND USE THEREOF
-
Provided herein are Itraconazole analogs. Also provided herein are methods of inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis and treatment of disease with Itraconazole analogs.
- -
-
Paragraph 0261
(2013/03/26)
-
- Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries
-
To find HDAC8-selective inhibitors, we designed a library of HDAC inhibitor candidates, each containing a zinc-binding group that coordinates with the active-site zinc ion, linked via a triazole moiety to a capping structure that interacts with residues on the rim of the active site. These compounds were synthesized by using click chemistry. Screening identified HDAC8-selective inhibitors including C149 (IC50 = 0.070 μM), which was more potent than PCI-34058 (6) (IC50 = 0.31 μM), a known HDAC8 inhibitor. Molecular modeling suggested that the phenylthiomethyl group of C149 binds to a unique hydrophobic pocket of HDAC8, and the orientation of the phenylthiomethyl and hydroxamate moieties (fixed by the triazole moiety) is important for the potency and selectivity. The inhibitors caused selective acetylation of cohesin in cells and exerted growth-inhibitory effects on T-cell lymphoma and neuroblastoma cells (GI50 = 3-80 μM). These findings suggest that HDAC8-selective inhibitors have potential as anticancer agents.
- Suzuki, Takayoshi,Ota, Yosuke,Ri, Masaki,Bando, Masashige,Gotoh, Aogu,Itoh, Yukihiro,Tsumoto, Hiroki,Tatum, Prima R.,Mizukami, Tamio,Nakagawa, Hidehiko,Iida, Shinsuke,Ueda, Ryuzo,Shirahige, Katsuhiko,Miyata, Naoki
-
p. 9562 - 9575
(2013/01/16)
-
- Itraconazole Side Chain Analogues: Structure-Activity Relationship Studies for Inhibition of Endothelial Cell Proliferation, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Glycosylation, and Hedgehog Signaling
-
Itraconazole is an antifungal drug that was recently found to possess potent antiangiogenic activity and anti-hedgehog (Hh) pathway activity. To search for analogues of itraconazole with greater potency and to understand the structure-activity relationship in both antiangiogenic and Hh targeting activity, 25 itraconazole side chain analogues were synthesized and assayed for inhibition of endothelial cell proliferation and Gli1 transcription in a medulloblastoma (MB) culture. Through this analysis, we have identified analogues with increased potency for inhibiting endothelial cell proliferation and the Hh pathway, as well as VEGFR2 glycosylation that was recently found to be inhibited by itraconazole. An SAR analysis of these activities revealed that potent activity of the analogues against VEGFR2 glycosylation was generally driven by side chains of at least four carbons in composition with branching at the α or β position. SAR trends for targeting the Hh pathway were divergent from those related to HUVEC proliferation or VEGFR2 glycosylation. These results also suggest that modification of the sec-butyl side chain can lead to enhancement of the biological activity of itraconazole.
- Shi, Wei,Nacev, Benjamin A.,Aftab, Blake T.,Head, Sarah,Rudin, Charles M.,Liu, Jun O.
-
supporting information; experimental part
p. 7363 - 7374
(2011/12/04)
-
- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
-
Disclosed herein are cannabinoid receptor ligands of formula (I) wherein A1, A5, Rx, X4, and z are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
- -
-
Page/Page column 69
(2010/04/23)
-
- An unexpected example of protein-templated click chemistry
-
(Figure Presented) It all happened with a click: In a search for histone deacetylase (HDAC) inhibitors using in situ click chemistry, the first example of protein-Cu acceleration of the azide-alkyne cycloaddition reaction was uncovered. The copper center
- Suzuki, Takayoshi,Ota, Yosuke,Kasuya, Yuki,Mutsuga, Motoh,Kawamura, Yoko,Tsumoto, Hiroki,Nakagawa, Hidehiko,Finn,Miyata, Naoki
-
supporting information; experimental part
p. 6817 - 6820
(2010/12/19)
-
- Peptide deformylase inhibitors with retro-amide scaffold: Synthesis and structure-activity relationships
-
Peptide deformylase (PDF) is a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins. Thus inhibition of PDF activity is considered to be one of the most effective antibiotic strategies. Reported herein are the synthesis
- Lee, Seung Kyu,Choi, Kwang Hyun,Lee, Sang Jae,Suh, Se Won,Kim, B. Moon,Lee, Bong Jin
-
body text
p. 4317 - 4319
(2010/10/03)
-
- PYRIDAZINONE COMPOUNDS
-
The invention is directed to pyridazinone compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.
- -
-
Page/Page column 69
(2008/12/07)
-
- PHENYL COMPOUNDS
-
Compounds of formula (I) or derivatives thereof: wherein A, B, Z, R, R, R, R, R, and R are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.
- -
-
-
- Benzazine derivatives as phosphodiesterase 4 inhibitors
-
Compounds of formula I: wherein A is a heterocycle containing a nitrogen atom and optionally saturated or unsaturated and optionally further substituted by an oxo group (═O); R is: hydrogen, cyano, (C1-4)alkoxycarbonyl, carbamoyl; optionally substituted (C4-7)-cycloalkyl, aryl or heterocycle; (C1-8)alkyl, (C2-8)alkenyl or (C2-8)alkynyl optionally branched and/or substituted by (C4-7) cycloalkyl, aryl or heterocycle; aryloxy, heterocyclyloxy, aryl(C1-4)alkoxy, heterocyclyl(C1-4)alkoxy, amino substituted by one or two (C1-4)alkyl group(s), aryl-amino, heterocyclyl-amino, aryl(C1-4)alkyl-amino, or heterocyclyl(C1-4)alkylamino; Y is methylene or ethylene; W is an optionally substituted aryl or heterocycle; R1is hydrogen, (C4-7)cycloalkyl or a (C2-8)alkyl, (C2-8)alkenyl or (C2-8)alkynyl group optionally substituted by hydroxy, oxo, (C4-7)cycloalkyl, aryl or heterocycle, and optionally interrupted by one or more heteroatom(s) or heterogroup(s); R2is a (C1-6)alkyl or polyfluoro(C1-6)alkyl group; the N→O derivatives of the compounds of formula I and the pharmaceutically acceptable salts thereof. The compounds of formula (I) are PDE 4 inhibitors and may be used in compositions and methods involving PDE 4 inhibition.
- -
-
-
- Kinetics and mechanism of the aminolysis of cycloalkylmethyl arenesulfonates
-
Nucleophilic substitution reactions of cycloalkylmethyl arenesulfonates (CmH2n-1 CH2OSO2C6H4Z) with anilines (XC6H4NH2) in methanol at 65.0 °C were studied. The reactivity order (n=4>6>7>5) reflects largely the order of steric effect of the ring size (SEs term) except for n=5, which exhibits the least reactivity. This reversal of the order for n=5 is considered to result from large rate retardation due to polar effect of the ρ*σ* term. Application of the Taft equation to the rate data for n=5 and 6 gives ρ=17·4 and 5=2·3 with correlation coefficient of 0·90. The σ* values for n=4 and 7 are estimated to be - 0·23 and - 0·11, respectively. The positive ρxz values of ca 0·3 are consistent with previous results for the reactions at primary reaction centers.
- Oh, Hyuck Keun,Song, Se Jeong,Jo, Dong-Soo,Lee, Ikchoon
-
-