- An Assessment of the Causes of the "Cesium Effect"
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Cesium alkanoates (chiefly the propionate) have been investigated for their solubility, nucleophilic, reactivity and degree of ion pairing in dimethylformamide (DMF) and, in some cases, dimethyl sulfoxide (DMSO) solutions. 133Cs NMR has been used to establish the degree of ion pairing.From the data obtained it is concluded that the cesium ion is virtually completely solvated and that the carboxylates are essentially free and highly reactive.The consequences of this effect on macrocyclization by means of nucleophilic substitution are discussed.
- Dijkstra, Gerard,Kruizinga, Wim H.,Kellogg, Richard M.
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Read Online
- Electrochemical Deoxygenative Thiolation of Preactivated Alcohols and Ketones
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This work describes an electrochemically promoted nickel-catalyzed deoxygenative thiolation of alcohols and ketones under mild conditions. Excellent substrate tolerance and good chemical yields can be achieved by graphene/nickel foam electrodes in an undivided cell. Further study to gain mechanistic insight into this electrochemical cross-coupling has been carried out.
- Zhang, Feng,Wang, Yang,Wang, Yi,Pan, Yi
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supporting information
p. 7524 - 7528
(2021/10/02)
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- Identification of organophosphorus simulants for the development of next-generation detection technologies
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Organophosphorus (OP) chemical warfare agents (CWAs) represent an ongoing threat but the understandable widespread prohibition of their use places limitations on the development of technologies to counter the effects of any OP CWA release. Herein, we describe new, accessible methods for the identification of appropriate molecular simulants to mimic the hydrogen bond accepting capacity of the PO moiety, common to every member of this class of CWAs. Using the predictive methodologies developed herein, we have identified OP CWA hydrogen bond acceptor simulants for soman and sarin. It is hoped that the effective use of these physical property specific simulants will aid future countermeasure developments.
- Ellaby, Rebecca J.,Clark, Ewan R.,Allen, Nyasha,Taylor, Faith R.,Ng, Kendrick K. L.,Dimitrovski, Milan,Chu, Dominique F.,Mulvihill, Daniel P.,Hiscock, Jennifer R.
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p. 2008 - 2014
(2021/03/16)
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- TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS
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Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.
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Page/Page column 410-411
(2020/10/21)
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- Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis
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Calcium dependent protein kinase 1 (CDPK1) is an essential Ser/Thr kinase that controls invasion and egress by the protozoan parasite Toxoplasma gondii. The Gly gatekeeper of CDPK1 makes it exquisitely sensitive to inhibition by small molecule 1H-pyrazolo
- Janetka, James W.,Hopper, Allen T.,Yang, Ziping,Barks, Jennifer,Dhason, Mary Savari,Wang, Qiuling,Sibley, L. David
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supporting information
p. 6144 - 6163
(2020/07/10)
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- CEREBLON BINDERS FOR THE DEGRADATION OF IKAROS
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The present invention provides cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway along with their use in therapeutic applications as described herein.
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Page/Page column 310
(2019/10/23)
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- Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity
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Wogonin, a natural product isolated from the plant Scutellaria baicalensis, has been shown to be a potent and selective inhibitor of CDK9. With the purpose of investigating the activity and selectivity of this chemical scaffold, several series of wogonin derivatives were prepared and screened for CDK9 inhibition and cellular antiproliferative activity. Among these compounds, the drug-like compound 51 showed potent activity against CDK9 (IC50 = 19.9 nM) and MV4-11 cell growth (IC50 = 20 nM). In addition, compound 51 showed much improved physicochemical properties, such as water solubility, compared with the parent compound wogonin. The follow-up studies showed that the compound 51 is selective toward CDK9-overexpressing cancer cells over normal cells. Preliminary mechanism studies on the anticancer effect indicated that 51 inhibited the proliferation of MV4-11 cells via caspase-dependent apoptosis. In addition, highlighted compound 51 showed significant antitumor activity in mouse acute myeloid leukemia (AML) models without producing apparent toxic effects in vivo, which gave us a new tool for further investigation of CDK9-targeted inhibitor as a potential antitumor drug especially for AML.
- Wang, Jubo,Li, Tinghan,Zhao, Tengteng,Wu, Tizhi,Liu, Chuang,Ding, Hong,Li, Zhiyu,Bian, Jinlei
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p. 782 - 801
(2019/06/25)
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- AMINOPYRIDINE DERIVATIVES AS TAM FAMILY KINASE INHIBITORS
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Provided herein are aminopyridine derivatives and pharmaceutical compositions that are useful as TAM family kinase inhibitors.
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Page/Page column 75
(2015/06/11)
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- Iron(III)-catalyzed halogenations by substitution of sulfonate esters
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A novel halogenation reaction from sulfonates catalyzed by iron(III) is described. The reaction can be performed as a stoichiometric or a catalytic version. This reaction provides a convenient strategy for the efficient access to structurally diverse secondary chlorides, bromides and iodides. The stereochemical course of the reaction is governed by the substrate and the experimental conditions. Secondary alcohols modified as quisylates or pysylates are substantially more reactive. Aliphatic quisylates proceed with overall inversion of configuration under catalytic conditions. Chemoselectivity in bismesylates was observed in favour of the secondary mesylate. Additionally, based on the experimental results, a possible catalytic cycle for the halogenation has been proposed.
- Ortega, Nuria,Feher-Voelger, Andres,Brovetto, Margarita,Padron, Juan I.,Martin, Victor S.,Martin, Tomas
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supporting information; experimental part
p. 963 - 972
(2011/06/20)
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- PYRAZOLE COMPOUNDS AS JAK INHIBITORS
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The present invention relates to compounds of formula (I), wherein R1, R2, R1a, R1b have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.
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Page/Page column 43
(2011/11/13)
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- Novel convenient synthesis of biologically active esters of hydroxylamine
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Alkylation of ethyl N-hydroxyacetimidate with readily available methanesulfonates of functionally substituted alcohols and subsequent deprotection of aminooxy group is a novel and convenient method to prepare functionally substituted esters of hydroxylamine with high overall yield. This approach is a good alternative to wellknown reaction of N-hydroxyphthalimide with alcohols under the Mitsunobu conditions. The properties of ethoxyethylidene protection of aminooxy group on the contrary to that of N-alkoxyphthalimide group allow to perform a wide spectra of the transformations in the radical of N-protected hydroxylamine derivatives. This is essential for synthetic strategies consisting in the introduction of N-protected aminooxy group at one of the first steps of synthesis and subsequent transformations of the radical. The inhibitory effect of one of the newly synthesized compound, 1-guanidinooxy-3-aminopropane (GAPA), was compared with that of well-known inhibitors of ornithine decarboxylase namely, α-difluoromethylornithine (DFMO) and 1-aminooxy-3-aminopropane (APA) on Leishmania donovani, a protozoan parasite that causes visceral leishmaniasis. GAPA, on the contrary with APA and DFMO, in micromolar concentrations, inhibited the growth of both amastigotes and promastigotes of sodium antimony gluconate-resistant forms of L. donovani. Springer-Verlag 2009.
- Khomutov, Maxim A.,Mandal, Swati,Weisell, Janne,Saxena, Neiha,Simonian, Alina R.,Vepsalainen, Jouko,Madhubala, Rentala,Kochetkov, Sergey N.
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scheme or table
p. 509 - 517
(2010/11/05)
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- SPIROINDOLINONE DERIVATIVES
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There are provided compounds of the formula and pharmaceutically acceptable salts and esters thereof wherein W, V, X, Y, A, R and R' are as described herein. The compounds are useful as anticancer agents.
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Page/Page column 101
(2009/07/03)
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- An efficient one-pot conversion of THP and TMS ethers to sulfonate esters using FeCl3-montmorillonite K-10 clay
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Various tetrahydropyranyl and trimethylsilyl ethers are efficiently transformed into the corresponding sulfonate esters with sulfonyl chlorides in the presence of FeCl3-Montmorillonite K-10 clay.
- Movassagh, Barahman,Shokri, Salman
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p. 763 - 765
(2007/10/03)
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- Montmorillonite clay catalyzed tosylation of alcohols and selective monotosylation of diols with p-toluenesulfonic acid: An enviro-economic route
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An enviro-economic route for tosylation of alcohols and selective monotosylation of diols in good yield directly using p-toluenesulfonic acid together with metal-exchanged montmorillonite instead of p-toluenesulfonyl chloride or p-toluenesulfonic anhydrid
- Choudary, Boyapati M.,Chowdari, Naidu S.,Kantam, Mannepalli L.
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p. 7291 - 7298
(2007/10/03)
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- Transition metals in selective hydrocarbon oxygenation catalysis: Kinetic studies of the reactions of cyclohexylhydroperoxide under 'Gif conditions
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IronQII) chloride in the presence of excess H2C>2 in 10:1 pyridine-acetic acid catalyses the clean conversion of cyclohexylhydroperoxide to cyclohexanone on the same time scale (hours) as observed for the latter stages of the Barton GoAggll system for the oxygenation of cyclohexane. The addition of one equivalent of picolinic acid/FeIII causes a significant increase (10 fold) in the conversion rate (no change in products) paralleling the rate enhancing effect observed in the Feln-picolinate-H202 (GoAggUI) oxygenating system. The Fe1" catalysed reaction in the absence of t-4Oj. however, is totally different with evidence of a linear induction period before the onset of product autocatalysis by the ketone. Here only a very slight rate enhancement is seen on adding picolinic acid and a different mechanism may be relevant. These and other observations have implications for the nature of reactions taking place in typical 'Gif systems.
- Mark, Scott B.,Richens, David T.
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p. 821 - 836
(2007/10/03)
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- Methods of using α-phosphonosulfonate squalene synthetase inhibitors including the treatment of atherosclerosis and hypercholesterolemia
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α-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula STR1 wherein R2 is OR5 or R5a ; R3 and R5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.
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- Direct Spectroscopic Detection of Sulfonyloxy Radicals and First Measurements of Their Absolute Reactivities
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Two sulfonyloxyl radicals, CH3S(=O)2O., 2a, and 3-CF3C6H4S(=O)2O., 2b, have been generated by 308-nm laser flash photolysis (LFP) of their parent symmetrical peroxides in CH3CN solution, in which they have lifetimes of 7-20 μs.Both radicals exhibit a broad, structureless absorption similar to that known for SO4.- with λmax ca. 450 nm.This absorption can be bleached for 2a but not for 2b by firing a second laser at 480 nm, presumably reflecting a photoinduced cleavage of the H3C-SO3. bond.Radicals 2a and 2b react with the acetonitrile solvent by abstraction of a hydrogen atom, kH ca. 1.6*105 M-1 s-1, kH/kD ca. 2.0.Bimolecular rate constants for attack of these radicals on cyclohexane (viz., 1.9*108 and 6.5*108 M-1 s-1 for 2a and 2b, respectively) and chloroform (viz. ca., 3*105 M-1 s-1 for both) demonstrate that they are more reactive than almost all other oxygen-centered radicals.Product studies demonstrate that both the photodecomposition and the thermal decomposition of the parent peroxides yield the corresponding sulfonyloxy radicals, a result that contrasts with that we have previously obtained for the decomposition of 2, which yields radicals on photolysis but few if any radicals on thermolysis.Semiempirical AM1/PM3-UHF calculations on 2a are also reported.
- Korth, Hans-Gert,Neville, Anthony G.,Lusztyk, Janusz
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p. 8835 - 8839
(2007/10/02)
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- The use of nitrones in the synthesis of anatoxin-a, very fast death factor
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The synthesis of anatoxin-a (1) was completed by using the cycloaddition of 1-pyrroline-1-oxide (2) onto dienol (6), a reaction which proceeded with high stereoselectivity, regioselectivity, and site selectivity. The resultant adduct (i.e. 7) was oxidized to a second nitrone (i.e. 8) which undergoes a second closure to afford cycloadduct 9a with regiospecificity. The conversion of 9a into anatoxin-a hydrochloride (1 · HCl) was both direct and efficient.
- Tufariello,Meckler,Pushpananda,Senaratne
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p. 3447 - 3453
(2007/10/02)
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