23473-74-7Relevant academic research and scientific papers
Immobilization of ruthenium catalysts for allylations with allyl alcohol
Van Rijn, Jimmy A.,Bouwman, Elisabeth,Drent, Eite
, p. 26 - 34 (2010)
[RuCp(PP)]+ complexes active for allylation of alcohols with allyl alcohol as the allylating agent were immobilized on solid supports. Two different immobilization methods have been applied: (1) via electrostatic interactions of the cationic complex on ion-exchange resins, where the anion is present on the support and (2) via a coordination bond with a ligand covalently-bound on the support. Both methods give high yields of immobilized complex through relatively simple procedures. The catalysts immobilized via ionic interactions prove to be able to allylate both 1-octanol and 4-tert-butylphenol with very low leaching of the catalyst, thus forming allyl octyl ether and C-allylated phenol, respectively. The accumulation of water in the highly hydrophilic resin precludes the O-allylation of phenol and also retards the C-allylation reaction. The catalysts immobilized via a coordination bond are not hydrophilic; with these catalysts selective O-allylation of phenols is achieved, with recycling of the catalysts over multiple runs. Leaching of the catalyst from the support is somewhat higher than for the electrostatically-bound catalyst and quarternisation (allylation) of the excess of phosphine groups present on the support plays an important role in the activity of the immobilized catalysts for the allylation reaction.
Ecofriendly Claisen rearrangement of allyl-4-tert-butylphenyl ether using heteropolyacid supported on hexagonal mesoporous silica
Yadav, Ganapati D.,Lande, Sharad V.
, p. 547 - 554 (2005)
The Claisen rearrangement of allyl phenyl ethers is a valuable reaction in organic synthesis having a variety of applications in perfumes, flavours, pharmaceuticals, and intermediate industries. The replacement of traditional environmentally threatening h
Novel potent (dihydro)benzofuranyl piperazines as human histamine receptor ligands – Functional characterization and modeling studies on H3 and H4 receptors
Corrêa, Michelle F.,Balico-Silva, André L.,Kiss, Dóra J.,Fernandes, Gustavo A.B.,Maraschin, Jhonatan C.,Parreiras-e-Silva, Lucas T.,Varela, Marina T.,Sim?es, Sarah C.,Bouvier, Michel,Keser?, Gy?rgy M.,Costa-Neto, Claudio M.,Fernandes, Jo?o Paulo S.
, (2020/12/21)
Histamine acts through four different receptors (H1R-H4R), the H3R and H4R being the most explored in the last years as drug targets. The H3R is a potential target to treat narcolepsy, Parkinson's disease, epilepsy, schizophrenia and several other CNS-related conditions, while H4R blockade leads to anti-inflammatory and immunomodulatory effects. Our group has been exploring the dihydrobenzofuranyl-piperazines (LINS01 series) as human H3R/H4R ligands as potential drug candidates. In the present study, a set of 12 compounds were synthesized from adequate (dihydro)benzofuran synthons through simple reactions with corresponding piperazines, giving moderate to high yields. Four compounds (1b, 1f, 1g and 1h) showed high hH3R affinity (pKi > 7), compound 1h being the most potent (pKi 8.4), and compound 1f showed the best efficiency (pKi 8.2, LE 0.53, LLE 5.85). BRET-based assays monitoring Gαi activity indicated that the compounds are potent antagonists. Only one compound (2c, pKi 7.1) presented high affinity for hH4R. In contrast to what was observed for hH3R, it showed partial agonist activity. Docking experiments indicated that bulky substituents occupy a hydrophobic pocket in hH3R, while the N-allyl group forms favorable interactions with hydrophobic residues in the TM2, 3 and 7, increasing the selectivity towards hH3R. Additionally, the importance of the indole NH in the interaction with Glu5.46 from hH4R was confirmed by the modeling results, explaining the affinity and agonistic activity of compound 2c. The data reported in this work represent important findings for the rational design of future compounds for hH3R and hH4R.
Novel potent vasodilating agents: Evaluation of the activity and potency of LINS01005 and derivatives in rat aorta
Ginoza, Milton,Fernandes, Gustavo A.B.,Corrêa, Michelle F.,Fernandes, Jo?o Paulo S.
, (2019/12/11)
Cardiovascular diseases (CVDs) present high prevalence rates in the current world. It is estimated that approximately one-third of the global deaths are related to CVDs, and thus there is still a need for novel drugs to treat these disorders. We serendipitously discovered that LINS01005 (5a) is a potent vasodilating agent in rat aorta, and therefore a set of analogues were evaluated for the vasodilating potency in Wistar and SHR rat thoracic aorta precontracted with norepinephrine, with endothelium intact (E+) or denuded (E–) aortic rings. Compounds 5a and 5b were the most potent, showing submicromolar potency for endothelium intact vessels (EC50 853 and 941 nM, respectively) and micromolar values for E– vessels (EC50 2.4 and 7.1 μM, respectively). These compounds were indeed significantly more potent vasodilating agents in SHR-derived aortic rings (p 50 2.4 nM (E+) 9.0 nM (E–)] and 5b [EC50 20 nM (E+) 2.1 μM (E–)]. SAR analysis though PCA and HCA were performed, suggesting that N-phenylpiperazine is essential to the activity, while increasing volume in the substituted aromatic moiety is detrimental to the potency. This is the first report of the vasodilating properties of such compounds, and studies regarding the mechanism of action are in progress in our group.
Profiling of LINS01 compounds at human dopamine D2 and D3 receptors
Corrêa, Michelle F,Reiner, David,Fernandes, Gustavo A B,Varela, Marina T,Aranha, Cecília M S Q,Stark, Holger,Fernandes, Jo?o Paulo S
, (2019/12/26)
Abstract: Histamine and dopamine neuronal pathways display interesting overlapping in the CNS, especially in the limbic areas, making them very attractive to designing drugs with synergistic and/or additive effects. The roles of these systems to treat schizophrenia, drug addiction, Parkinson’s and Alzheimer’s diseases, among others are widely known. The LINS01 compounds were previously reported as histamine H3 receptor (H3R) antagonists and some of them are under evaluation in rodent memory models. Considering their pharmacological potential and similarities to literature dopamine D2 receptor (D2R) and dopamine D3 receptor (D3R) ligands, this work aimed to evaluate these compounds as ligands these receptors by using [3H]spiperone displacement assays. A set of 11 compounds containing the dihydrobenzofuranyl-piperazine core with substituents at 5-position of dihydrobenzofuran ring and at the piperazine nitrogen was examined. The compounds showed low to moderate affinities at both, D2R and D3R. N-Phenyl compounds LINS01005 (1d), LINS01011 (1h), LINS01012 (1i) and LINS01016 (1k) showed the highest affinities in the set to D3R (Ki 0.3–1.5 μM), indicating that N-phenylpiperazine moiety increases the affinity to this receptor subtype with some selectivity, since they showed lower affinities to D2R (Ki 1.3–5.5 μM). With the LINS01 compounds showing moderate binding affinity, new lead structures for optimization with regards to combined H3R and D2R/D3R-ligands are provided. Graphic abstract: Histamine and dopamine neuronal pathways display interesting overlapping in the CNS, and thus LINS01 compounds previously reported as histamine H3 receptor antagonists were evaluated as dopamine D2R and D3R ligands. The compounds showed micromolar affinities to both receptors[Figure not available: see fulltext.].
Asymmetric Carboxycyanation of Aldehydes by Cooperative AlF/Onium Salt Catalysts: from Cyanoformate to KCN as Cyanide Source
Brodbeck, Daniel,álvarez-Barcia, Sonia,Meisner, Jan,Broghammer, Florian,Klepp, Julian,Garnier, Delphine,Frey, Wolfgang,K?stner, Johannes,Peters, René
, p. 1515 - 1524 (2019/01/09)
Asymmetric 1,2-additions of cyanide yield enantioenriched cyanohydrins as versatile chiral building blocks. Next to HCN, volatile organic cyanide sources are usually used. Among them, cyanoformates are more attractive on technical scale than TMSCN for cos
Pharmacological and SAR analysis of the LINS01 compounds at the human histamine H1, H2, and H3 receptors
Corrêa, Michelle Fidelis,Barbosa, álefe Jhonatas Ramos,Fernandes, Gustavo Ariel Borges,Baker, Jillian G.,Fernandes, Jo?o Paulo dos Santos
, p. 89 - 95 (2018/09/27)
Histamine is a transmitter that activates the four receptors H1R to H4R. The H3R is found in the nervous system as an autoreceptor and heteroreceptor, and controls the release of neurotransmitters, making it a potential drug target for neuropsychiatric conditions. We have previously reported that the 1-(2,3-dihydro-1-benzofuran-2-yl)methylpiperazines (LINS01 compounds) have the selectivity for the H3R over the H4R. Here, we describe their pharmacological properties at the human H1R and H2R in parallel with the H3R, thus providing a full analysis of these compounds as histamine receptor ligands through reporter gene assays. Eight of the nine LINS01 compounds inhibited H3R-induced histamine responses, but no inhibition of H2R-induced responses was seen. Three compounds were weakly able to inhibit H1R-induced responses. No agonist responses were seen to any of the compounds at any receptor. SAR analysis shows that the N-methyl group improves H3R affinity while the N-phenyl group is detrimental. The methoxy derivative, LINS01009, had the highest affinity.
An Aluminum Fluoride Complex with an Appended Ammonium Salt as an Exceptionally Active Cooperative Catalyst for the Asymmetric Carboxycyanation of Aldehydes
Brodbeck, Daniel,Broghammer, Florian,Meisner, Jan,Klepp, Julian,Garnier, Delphine,Frey, Wolfgang,K?stner, Johannes,Peters, René
supporting information, p. 4056 - 4060 (2017/03/27)
Al?F bonds are among the most stable σ bonds known, exhibiting an even higher bond energy than Si?F bonds. Despite a stability advantage and a potentially high Lewis acidity of Al?F complexes, they have not been described as structurally defined catalysts
Investigation on Claisen rearrangement of allyl phenyl ethers in near-critical water
Xiao, Shangyou,He, Yi,Xu, Guang,Liu, Qi
, p. 3299 - 3305 (2015/06/08)
Catalyst-free Clasien rearrangement of allyl phenyl ethers were investigated in near-critical water. The effects on the reaction in near-critical water and conventional conditions were compared. The results demonstrate that near-critical water could greatly accelerate the Claisen rearrangement of allyl phenyl ethers. This process is simple, fast, efficient and environmentally benign.
A diastereoselective route to trans-2-aryl-2,3-dihydrobenzofurans through sequential cross-metathesis/isomerization/allylboration reactions: Synthesis of bioactive neolignans
Hemelaere, Rémy,Carreaux, Fran?ois,Carboni, Bertrand
supporting information, p. 2470 - 2481 (2015/04/22)
A new highly diastereoselective synthetic route to trans-2,3-dihydrobenzofuran systems, in particular those bearing an aryl substituent at the C2 position, is described. The cornerstone of our strategy is the implementation of a cross-metathesis/isomerization/allylboration sequence starting from 2-allyl-substituted phenols and aldehydes. After an intramolecular Mitsunobu cyclization step, the anti-homoallylic alcohols allow the synthesis of the desired skeleton in a stereoselective fashion. As an illustration, we used this strategy for the preparation of the dihydrodehydrodiconiferyl alcohol (1a), a natural dihydrobenzofuran neolignan, as well as for a formal synthesis of its O-demethylated derivative 1b. An enantioselective version of this approach employing a chiral phosphoric acid in the allylboration step is also studied.
