- Copper-Mediated Dichotomic Borylation of Alkyne Carbonates: Stereoselective Access to (E)-1,2-Diborylated 1,3-Dienes versus Traceless Monoborylation Affording α-Hydroxyallenes
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A mild copper-mediated protocol has been developed for borylation of alkynyl cyclic carbonates. Depending on the nature of the borylating reaction partner, either stereoselective diborylation of the propargylic surrogate takes place, providing convenient access to (E)-1,2-borylated 1,3-dienes, or traceless monoborylation occurs, which leads to α-hydroxyallenes as the principal product. The dichotomy in this borylation protocol has been scrutinized by several control experiments, illustrating that a relatively small change in the diboron(4) reagent allows for competitive alcohol-assisted protodemetalation to forge an α-hydroxyallene product under ambient conditions.
- Guo, Kun,Kleij, Arjan W.
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supporting information
p. 4901 - 4906
(2021/01/21)
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- SMALL MOLECULE ACTIVATORS OF NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NAMPT) AND USES THEREOF
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Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.
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Paragraph 01095
(2018/08/03)
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- Non-imidazole histamine H3 ligands. Part VI. Synthesis and preliminary pharmacological investigation of thiazole-type histamine H3-receptor antagonists with lacking a nitrogen nucleus in the side chain
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Background: Antagonists to the H3 receptor are considered to be potential drugs for the treatment of Alzheimer's disease, attention deficit-hyperactive disorder, memory and learning deficits, and epilepsy. The initial development of potent H3 receptor antagonists focused on extensive modification of the natural ligand histamine. However, it has appeared that imidazole-containing ligands are associated with inhibition of cytochrome P450 enzymes, caused by imidazole nitrogen complexation to heme iron in the active site of the enzyme. For these reasons, the development of potent non-imidazole H3 receptor antagonists was eagerly awaited. Objective: Previously, we reported the synthesis and pharmacological in vitro characterization of series of potent histamine H3-receptor non-imidazole antagonists belonging to the class of substituted 2-thiazol-4-n-propylpiperazines. A lead compound 1 of this family was a derivative carrying the ethylaminomethylpropyl chain. Methods: With the aim of increasing lipophilicity, that will help the ligands to cross the blood-brain barrier, we synthesized a series of new 2-thiazol-4-n-propylpiperazines where the ethylaminomethylpropyl moiety was replaced by a p-substituted-, an unsubstituted benzene ring, and ω-phenylalkyl substituent at positions 4 and 5 of thiazole ring, respectively. All compounds were tested for H3 antagonistic effects in vitro using the electrically contracting guinea pig jejunum. Results: The most active compounds of presented series 3d, 3e, and 3j showed lower affinity than the lead compound 1 and additionally, derivatives 3d and 3j possessed weak, competitive H1-antagonistic activity. This is in contrast to the lead compound 1 that has no affinity at H1 receptor. Conclusion: We can conclude that a side chain in the 2-thiazol-4-n-propylpiperazine scaffold should contain a basic center and should be present at a favorable position 5 of thiazole ring.
- Guryn, Roman,Staszewski, Marek,Kopczacki, Piotr,Walczyński, Krzysztof
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- Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors
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A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2,3-d]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broad-spectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC50of 36?nM and showed a submicromolar mean GI50value against NCI-60 cell lines. The interaction of 6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis.
- Lee, Ju-Hyeon,Shin, Sang Chul,Seo, Seon Hee,Seo, Young Ho,Jeong, Nakcheol,Kim, Chan-Wha,Kim, Eunice EunKyeong,Keum, Gyochang
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supporting information
p. 237 - 241
(2016/12/27)
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- Novel pyrrolo pyrimidine derivatives and composition for preventing or treating cancer comprising the same
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The present invention relates to a novel pyrrolo pyrimidine compound represented by chemical formula 1, pharmaceutically acceptable salt or hydrate thereof, a manufacturing method thereof, and a pharmaceutical composition comprising the compound for preventing or treating cancer. In chemical formula 1, R^1, R^2, R^3, R^4, R^5, and X are the same as defined in the specification.COPYRIGHT KIPO 2016
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Paragraph 0088; 0089; 0090
(2016/11/24)
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- Iridium-catalyzed isomerization/bromination of allylic alcohols: Synthesis of α-bromocarbonyl compounds
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α-Brominated ketones and aldehydes, with two adjacent electrophilic carbon atoms, are highly valuable synthetic intermediates in organic synthesis, however, their synthesis from unsymmetrical ketones is very challenging, and current methods suffer from low selectivity. We present a new, reliable, and efficient method for the synthesis of α-bromocarbonyl compounds in excellent yields and with excellent selectivities. Starting from allylic alcohols as the carbonyl precursors, the combination of a 1,3-hydrogen shift catalyzed by iridium(III) with an electrophilic bromination gives α-bromoketones and aldehydes in good to excellent yields. The selectivity of the process is determined by the structure of the starting allylic alcohol; thus, α-bromoketones formally derived from unsymmetrical ketones can be synthesized in a straightforward and selective manner. Synthon shuffle: An efficient and high-yielding synthetic route to prepare α-bromoketones and aldehydes is presented (see scheme, Cp=pentamethylcyclopentadienyl). The method relies on 1,3-hydrogen shift/bromination of allylic alcohols catalyzed by IrIII complexes. The products are obtained in excellent yields and as single constitutional isomers.
- Gomez, Antonio Bermejo,Erbing, Elis,Batuecas, Maria,Vazquez-Romero, Ana,Martin-Matute, Belen
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supporting information
p. 10703 - 10709
(2014/09/17)
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- A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: Structure-based design, synthesis, and biological evaluation
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In this work, we report a rational structure-based approach aimed at the discovery of new 2-aminoimidazoles as β-secretase inhibitors. Taking advantage of a microwave-assisted synthetic protocol, a small library of derivatives was obtained and biologicall
- Chiriano, Gianpaolo,De Simone, Angela,Mancini, Francesca,Perez, Daniel I.,Cavalli, Andrea,Bolognesi, Maria Laura,Legname, Giuseppe,Martinez, Ana,Andrisano, Vincenza,Carloni, Paolo,Roberti, Marinella
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supporting information; experimental part
p. 206 - 213
(2012/03/26)
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- IMIDAZOPYRIMIDINONES AND USES THEREOF
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable derivative, salt or prodrug thereof. The present invention further provides a method of treatment or prophylaxis of a viral infection in a subject comprising administering to said subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative, salt or prodrug thereof. Pharmaceutical compositions comprising a compound of formula (I) are also provided.
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Page/Page column 66
(2010/04/03)
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- HETEROCYCLIC GAMMA SECRETASE MODULATORS
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The invention relates to methods for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica and Down syndrome which comprise ad
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Page/Page column 35
(2010/06/11)
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- Direct asymmetric bromination of aldehydes catalyzed by a binaphthyl-based secondary amine: Highly enantio- and diastereoselective one-pot synthesis of bromohydrins
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One-pot stereoselective synthesis of bromohydrins as a useful chiral building block was achieved by the reaction of Grignard reagents with optically active α-bromoaldehydes, which were in situ generated by direct asymmetric bromination of aldehydes cataly
- Kano, Taichi,Shirozu, Fumitaka,Maruoka, Keiji
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supporting information; experimental part
p. 7590 - 7592
(2010/11/18)
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- PESTICIDES AND USES THEREOF
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The invention disclosed in this document is related to field of pesticides and their use in controlling pests. In particular compounds having the following formula are disclosed.
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Page/Page column 23
(2009/02/11)
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- A concise microwave-assisted synthesis of 2-aminoimidazole marine sponge alkaloids of the isonaamines series
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A short and efficient route to 1,4-substituted 2-aminoim-idazole alkaloids starting from the easily accessible 2-alkylami-nopyrimidines and α-bromo aldehydes is reported. The formation of the intermediate imidazo[l,2-a] pyrimidinium salts and subsequent cleavage were facilitated by microwave irradiation. Marine sponge alkaloids preclathridines A, C and isonaamines A, C, D were obtained in high yields using the optimized one-pot two-step procedure. Thieme Stuttgart.
- Ermolat'ev,Alifanov,Rybakov,Babaev,Van Der Eycken
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experimental part
p. 2083 - 2088
(2009/04/03)
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- Reductive cross-aldol reaction using bromoaldehyde and an aldehyde mediated by germanium(II): One-pot, large-scale protocol
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(Chemical Equation Presented) The reaction of α-bromoaldehyde with aldehyde in the presence of GeCl2-dioxane gave the syn-selective cross-aldol equivalent. A catalytic amount of Bu4NBr improved the yield and selectivity. The initially formed aldol adduct (β- germoxyaldehyde) did not suffer from over-reaction. This system enabled an intramolecular aldol reaction to give cyclic compounds effectively. One-pot synthetic methodology including bromination of aldehyde followed by cross-aldol reaction with the second aldehyde was successful on a large-scale.
- Yasuda, Makoto,Tanaka, Shin-Ya,Baba, Akio
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p. 1845 - 1848
(2007/10/03)
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- MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
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The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ("CFTR"), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators (I) or a pharmaceutically acceptable salt thereof, wherein: Ht is a 5-membered heteroaromatic ring containing 1-4 heteroatoms selected from O, S, N or NH, wherein said ring is optionally fused to a 6-membered monocyclic or 10-membered bicyclic carbocyclic or heterocyclic, aromatic or non-aromatic ring, wherein Ht is optionally substituted with w occurrences of -WRw, wherein w is 0-5; ring A is 3-7 membered monocyclic ring having 0-3 heteroatoms selected from O, S, N, or NH, wherein ring A is optionally substituted with q occurrences of QRQ; ring B is optionally fused to 5-6 membered carbocyclic or heterocyclic, aromatic or non-aromatic ring .
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Page/Page column 132-133; 133-134
(2010/02/13)
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- REACTIVITY OF α-ARYLSELENO-ALDEHYDES TOWARDS HALOGENS AND BENZENESELENENYL CHLORIDE
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Chlorination of α-seleno-aldehydes bearing an α-hydrogen gives selenium dichlorides which decompose into α-chloro α-seleno-aldehydes and α-chloroenal.Bromination, in all cases, and chlorination for the other α-seleno-aldehydes lead to the α-halogenoaldehydes.
- Paulmier, Claude,Outurquin, Francis,Plaquevent, Jean-Christophe
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p. 5893 - 5896
(2007/10/02)
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