16900-60-0Relevant articles and documents
On the synthesis of vinyl isonitriles
Baldwin, Jack E.,Chen, Deqi,Russell, Andrew T.
, p. 2389 - 2390 (1997)
A reversal of the stereochemistry of base mediated isomerisation of some isonitrile epoxides to hydroxy-vinyl isonitriles on changing from lithium diisopropylamide to lithium bis(trimethylsilyl)amide is reported and applied to a synthesis of racemic desepoxyaerocyanidin.
INSULIN CONJUGATES
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Paragraph 0580; 0588-0590; 0591, (2020/07/05)
The present invention relates to a conjugate comprising a sulfonamide of formula (I) and an active pharmaceutical ingredient such as an insulin analog comprising at least one mutation relative to the parent insulin, wherein the insulin analog comprises a mutation at position B16 which is substituted with a hydrophobic amino acid and/or a mutation at position B25 which is substituted with a hydrophobic amino acid. The present invention further relates to a sulfonamide of formula (A). Moreover, the present invention relates to an insulin analog comprising at least one mutation relative to the parent insulin.
A Sequential Homologation of Alkynes and Aldehydes for Chain Elongation with Optional 13C-Labeling
Brunner, Andreas,Hintermann, Lukas
, p. 2787 - 2792 (2016/02/27)
Terminal alkynes (RCCH) are homologated by a sequence of ruthenium-catalyzed anti-Markovnikov hydration of alkyne to aldehyde (RCH2CHO), followed by Bestmann-Ohira alkynylation of aldehyde to chain-elongated alkyne (RCH2CCH). Inverting the sequence by starting from aldehyde brings about the reciprocal homologation of aldehydes instead. The use of 13C-labeled Bestmann-Ohira reagent (dimethyl ((1-13C)-1-diazo-2-oxopropyl)phosphonate) for alkynylation provides straightforward access to singly or, through additional homologation, multiply 13C-labeled alkynes. The labeled alkynes serve as synthetic platform for accessing a multitude of specifically 13C-labeled products. Terminal alkynes with one or two 13C-labels in the alkyne unit have been submitted to alkyne-azide click reactions; the copper-catalyzed version (CuAAC) was found to display a regioselectivity of >50 000:1 for the 1,4- over the 1,5-triazine isomer, as shown analytically by 13C NMR spectroscopy.
Structural Analysis and Inclusion Mechanism of Native and Permethylated α-Cyclodextrin-Based Rotaxanes Containing Alkylene Axles
Akae, Yosuke,Koyama, Yasuhito,Sogawa, Hiromitsu,Hayashi, Yoshihiro,Kawauchi, Susumu,Kuwata, Shigeki,Takata, Toshikazu
supporting information, p. 5335 - 5341 (2016/04/09)
Native α-cyclodextrin- (α-CD) and permethylated α-CD (PMeCD)-based rotaxanes with various short alkylene chains as axles can be synthesized through a urea end-capping method. Native α-CD tends to form [3]- or [5]pseudorotaxanes and not [2]- or [4]pseudorotaxanes, which indicates that the coupled CDs act as a single fragment. End-capping reactions of the pseudorotaxanes with C18 and C24 axle lengths do not occur because the axle termini are covered by the densely stacked CDs. The number of PMeCDs on the pseudorotaxane is flexible and mainly depends on the axle length. Peracetylated α-CD (PAcCD)-based rotaxanes are synthesized through O-acetylation of the α-CD-based rotaxanes without any decomposition of the rotaxanated structures. The structures of PMeCD-based [3]- and [4]rotaxanes, and the molecular dynamics calculations on [3]pseudorotaxanes, indicate that the tail face of PMeCDs is regularly directed toward the axle termini. On the basis of the results obtained, it can be concluded that the directions and numbers of CDs in rotaxanes containing short alkylene chains depend on 1)the interactions between CDs, 2)the length of the alkylene axle, and 3)the interactions between the axle end and tail face of the CD. Come on in! Native and permethylated α-cyclodextrin (CD)-based rotaxanes with various short alkylene axles are synthesized with a urea end-capping method. The directions and number of the CD wheels depend on the interactions between CDs, the axle length, and the interactions between axle ends and the tail face of the CDs (see figure).
Identification of acyl protein thioesterases 1 and 2 as the cellular targets of the ras-signaling modulators palmostatin B and M
Rusch, Marion,Zimmermann, Tobias J.,Bürger, Marco,Dekker, Frank J.,G?rmer, Kristina,Triola, Gemma,Brockmeyer, Andreas,Janning, Petra,B?ttcher, Thomas,Sieber, Stephan A.,Vetter, Ingrid R.,Hedberg, Christian,Waldmann, Herbert
supporting information; experimental part, p. 9838 - 9842 (2011/12/02)
Finding the target: Activity-based proteomic profiling probes based on the depalmitoylation inhibitors palmostatin B and M (see picture) have been synthesized and were found to target acyl protein thioesterase 1 (APT1) and 2 (APT2) in cells. Copyright
DIYNE COMPOSITIONS
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Page/Page column 45, (2011/02/24)
A novel class of diyne compounds and diyne salts provided herein are effective and potent Olel protein inhibitors, useful for treating fungal pathogens. Compounds, fungicides and methods are provided as novel, potent and broad spectrum antifungal agents for treatment against a wide variety of fungal pathogens in humans and animals, and in the agricultural setting.
17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analogues
Falck, John R.,Wallukat, Gerd,Puli, Narender,Goli, Mohan,Arnold, Cosima,Konkel, Anne,Rothe, Michael,Fischer, Robert,Müller, Dominik N.,Schunck, Wolf-Hagen
supporting information; experimental part, p. 4109 - 4118 (2011/08/05)
17(R),18(S)-Epoxyeicosatetraenoic acid [17(R),18(S)-EETeTr], a cytochrome P450 epoxygenase metabolite of eicosapentaenoic acid (EPA), exerts negative chronotropic effects and protects neonatal rat cardiomyocytes against Ca 2+-overload with EC50 ≈ 1-2 nM. Structure-activity studies revealed that a cis-Δ11,12- or Δ14,15- olefin and a 17(R),18(S)-epoxide are minimal structural elements for antiarrhythmic activity whereas antagonist activity was often associated with the combination of a Δ14,15-olefin and a 17(S),18(R)-epoxide. Compared with natural material, the agonist and antagonist analogues are chemically and metabolically more robust and several show promise as templates for future development of clinical candidates.
Novel eicosanoid derivatives
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Page/Page column 40, (2010/08/07)
The present invention provides compounds (n-3 PUFA derivatives) of formula (I): that modulate conditions associated with cardiac damage, especially cardiac arrhythmias.
14,15-Epoxyeicosa-5,8,11-trienoic acid (14,15-EET) surrogates containing epoxide bioisosteres: Influence upon vascular relaxation and soluble epoxide hydrolase inhibition
Falck,Kodela, Ravinder,Manne, Rajkumar,Atcha, Krishnam Raju,Puli, Narender,Dubasi, Narsimhaswamy,Manthati, Vijay L.,Capdevila, Jorge H.,Yi, Xiu-Yu,Goldman, Daniel H.,Morisseau, Christophe,Hammock, Bruce D.,Campbell, William B.
supporting information; experimental part, p. 5069 - 5075 (2010/03/04)
All-cis-14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) is a labile, vasodilatory eicosanoid generated from arachidonic acid by cytochrome P450 epoxygenases. A series of robust, partially saturated analogues containing epoxide bioisosteres were synthesized and evaluated for relaxation of precontracted bovine coronary artery rings and for in vitro inhibition of soluble epoxide hydrolase (sEH). Depending upon the bioisostere and its position along the carbon chain, varying levels of vascular relaxation and/or sEH inhibition were observed. For example, oxamide 16 and N-iPr-amide 20 were comparable (ED50 1.7 μM) to 14,15-EET as vasorelaxants but were approximately 10-35 times less potent as sEH inhibitors (IC50 59 and 19 μM, respectively); unsubstituted urea 12 showed useful activity in both assays (ED50 3.5 μM, IC50 16 nM). These data reveal differential structural parameters for the two pharmacophores that could assist the development of potent and specific in vivo drug candidates.
Synthesis of carboxyl-tethered symmetric conjugated polyenes as fluorescent transmembrane probes of lipid bilayers
Quesada, Ernesto,Acuna, A. Ulises,Amat-Guerri, Francisco
, p. 1308 - 1318 (2007/10/03)
The synthesis of a new series of fluorescent transmembrane probes in which two hydrophilic methyl ester or carboxyl groups are connected by a polymethylene chain, with four, five or six conjugated double bonds in a central position, is reported. The length of the linear structures was designed to match the width of typical lipid bilayers. These bolaamphiphilic compounds result, with overall yields higher than 80%, from an easy PdII-catalyzed double cross-coupling between terminal acetylene esters and conjugated 1,ω-dihalopolyenes, followed by selective triple bond partial reduction with activated zinc, and iodine isomerization to the all-(E) isomer. An alternative approach, based on a Stille double cross-coupling between the appropriate all-(E)-ω-halopolyenes and (E)-bis(tributylstannyl)ethene, yielded mixtures that could not be resolved by standard chromatographic methods due to the presence of other simultaneous coupling reactions, which are also discussed in detail. Nevertheless, the Stille method can be of utility for the obtention of carbonyl-polyene conjugated analogs. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.