- A reassessment of mycophenolic acid as a lead compound for the development of inhibitors of chikungunya virus replication
-
Mycophenolic acid (MPA) has been previously reported as an inhibitor of the chikugunya virus (CHIKV) with an EC50 value of 0.2 μM. We used MPA as a lead compound designing and synthesizing a series of isatins and benzolactones in a typical medicinal chemistry program. The synthesis and testing of 19 derivatives produced compounds with no desired activity which prompted us to retest the lead compound, MPA. We can reveal that MPA shows no anti-CHIKV activity and therefore needs to be reassessed as a lead compound for this target.
- Rashad, Adel A.,Neyts, Johan,Leyssen, Pieter,Keller, Paul A.
-
p. 1294 - 1306
(2018/03/08)
-
- Palladium-catalyzed amination of aryl chlorides and bromides with ammonium salts
-
We report the palladium-catalyzed coupling of aryl halides with ammonia and gaseous amines as their ammonium salts. The coupling of aryl chlorides and ortho-substituted aryl bromides with ammonium sulfate forms anilines with higher selectivity for the primary arylamine over the diarylamine than couplings with ammonia in dioxane. The resting state for the reactions of aryl chlorides is different from the resting state for the reactions of aryl bromides, and this change in resting states is proposed to account for a difference in selectivities for reactions of the two haloarenes.
- Green, Rebecca A.,Hartwig, John F.
-
supporting information
p. 4388 - 4391
(2015/01/08)
-
- IMIDAZOLIDINEDIONE DERIVATIVES
-
The invention provides a compound of formula (Ia), and pharmaceutically acceptable salts thereof. The invention also provides use of the compounds or salts as modulators of Kv3.1 and/or Kv3.2, and in the treatment of diseases or disorders where a modulator of Kv3.1 and/or Kv3.2 is required, such as depression and mood disorders, hearing disorders, schizopherenea, substance abuse disorders, sleep disorders or epilepsy.
- -
-
Page/Page column 43
(2011/06/26)
-
- NOVEL TYROSINE KINASE INHIBITORS
-
Provided are compounds of the formula (I): or a stereoisomer, tautomer, salt, hydrate or prodrug thereof that modulate tyrosine kinase activity, compositions comprising the compounds and methods of their use.
- -
-
Page/Page column 70-71
(2009/10/22)
-
- Deactivation of heterogeneous hydrogenation catalysts by alcoholic solvents
-
Hydrogenations using supported metal catalysts are ubiquitous in organic chemistry; yet often times there is a lack of knowledge of key subtle mechanistic features of these reactions that can spell the difference between success or failure in a given synthetic application. Herein we detail an unexpected deactivation of certain heterogeneous hydrogenation catalysts caused by the typical solvent of choice for such reactions, simple aliphatic alcohols. This phenomenon was found to be general for several classes of substrates using either Raney Ni or supported Pd-catalysts. The characteristics of this phenomenon, including the reversibility of the catalyst deactivation upon exposure to air, are consistent with literature reports of alcohol decomposition on metal surfaces forming adsorbed CO.
- Singh, Utpal K.,Krska, Shane W.,Sun, Yongkui
-
p. 1153 - 1156
(2012/12/23)
-
- Methods of making 2,6-diaryl piperidine derivatives
-
Methods for preparing 2,6-diaryl piperidine derivatives are described. More particularly, 2,6-diaryl piperidines having formula 1-4 are prepared by cyclocondensation of an aryl or heteroaryl aldehyde with 1,3-acetonedicarboxylic acid.
- -
-
-
- SUBSTITUTED QUINAZOLINE DERIVATIVES AND THEIR USE AS INHIBITORS
-
The use of a compound of formula (I) 1 or a salt, ester or amide thereof; where X is O, or S, S(O) or S(O)2, or NR6 where R6 is hydrogen or C1-6 alkyl,; R5 is an optionally substituted 5-membered heteroaromatic ring, R1, R2 ,R3, R4 are independently selected from various specified moieties, in the preparation of a medicament for use in the inhibition of aurora 2 kinase. Certain compounds are novel and these, together with pharmaceutical compositions containing them are also described and claimed
- -
-
-
- 2,5-dimethylpyrrole protection facilitates copper(I)-mediated methoxylations of aryl iodides in the presence of anilines
-
Converting iodoanilines to the corresponding 2,5-dimethylpyrroles was found to facilitate CuCI-mediated methoxide substitution. Examples with ortho-, meta-, or para-relationships between the iodide and aniline are presented. Several other aniline blocking groups were investigated and found not to be successful in this sequence.
- Ragan, John A.,Makowski, Teresa W.,Castaldi, Michael J.,Hill, Paul D.
-
p. 1599 - 1603
(2007/10/03)
-
- Collisionally induced dissociation in the study of A-ring hydroxylated vitamin D type compounds
-
Colllslonally Induced dissociation (CID) is often used to determine the structure of ions based on comparison with the CID spectra of known ions. The latter are generated from Judiciously selected compounds taking into account basic principles of Ion chemistry. We report here on the use of this approach toward determination of the site of A-ring hydroxylation of vitamin D. Although not Intrinsically an aromatic compound, vitamin D gives rise in its mass spectrum to an aromatic methytstyryl cation at mlz 118. A-ring hydroxylated metabolites of vitamin D would thus Incorporate the extra OH group on the ion at mlz 118, shifting it to mlz 134. The position of substitution of the extra OH group on a metabolite could then be ascertained by comparing the CID spectrum of its mlz 134 fragment to those of the four possible (hydroxymethyl)styryl cations generated from synthesized authentic compounds. Because of their propensity to polymerize, these cations were generated in situ via the McLafferty rearrangement of the corresponding (hydroxyphenyl)ethanols. For optimum differentiation of Isomeric Ions, preparation of permethylated derivatives of vitamin D was necessary. The validity of the hypothesis was verified using 1,25-dihydroxy-vitamin D3 as a test compound. This method provides a viable approach for the characterization of A-ring hydroxylated metabolites of vitamin D as well as for related aromatic compounds.
- Young, David C.,Vouros, Paul,Holick, Michael F.,Higuchi, Tetsuo
-
p. 837 - 842
(2007/10/02)
-
- Benzofuran-2-ones and pharmaceutical compositions
-
The invention relates to novel furans, especially benzofuranones of the general formula STR1 in which R1 represents hydrogen or an aliphatic radical, R2 represents an amino group di-substituted by a divalent hydrocarbon radical, and the aromatic ring A may be additionally substituted, and their salts and/or isomers, processes for the manufacture of compounds of the formula (I) and their salts and isomers, pharmaceutical preparations containing these compounds, and their use as the active ingredients of medicaments as anti-inflammatory agents, analgesics or light-screening agents and/or for the manufacture of pharmaceutical preparations.
- -
-
-
- SYNTHETIC ANALOGS OF Peganum ALKALOIDS. I. SYNTHESIS OF METHOXY- AND HYDROXY-SUBSTITUTED DEOXYVASICINONES AND DEOXYPEGANINES
-
6-Methoxy-, 7-methoxy-, and 8-methoxydeoxyvasicinones have been synthesized by the reaction of substituted (3-methoxy-, 4-methoxy-, and 5-methoxy-) anthranilic acids with α-pyrrolidone.The demethylation of these compounds has given the corresponding hydroxy-substituted analogs of deoxyvasicinone, and the reduction of the products obtained with zinc in hydrochloric acid has given the hydroxy- and methoxy- analogs of deoxypeganine. 8-Hydrooxydeoxypeganine dimethyl-, ethyl-, and butylcarbamates have been obtained by the carbamoylation of 8-hydroxydeoxypeganine.
- Karimov, A.,Telezhenetskaya, M. V.,Yunusov, S. Yu.
-
p. 466 - 472
(2007/10/02)
-