37779-49-0Relevant articles and documents
Novel photochemical rearrangements of dihydro-1,3-thiazines
Bhatia, Shameem H.,Buckley, David M.,McCabe, Richard W.,Avent, Anthony,Brown, Robert G.,Hitchcock, Peter B.
, p. 569 - 574 (1998)
A series of 4-alkyl or 4-phenyl substituted 2,3-dihydro-6H-1,3-thiazine-5-carboxylates are synthesised and photolysed in toluene. The 4-methyl compound rearranges to a thiazolidine, which co-exists as an imino-tau tomer in solution. The 4-ethyl derivative
Homobenzylic Oxygenation Enabled by Dual Organic Photoredox and Cobalt Catalysis
McManus, Joshua B.,Griffin, Jeremy D.,White, Alexander R.,Nicewicz, David A.
supporting information, p. 10325 - 10330 (2020/07/27)
Activation of aliphatic C(sp3)-H bonds in the presence of more activated benzylic C(sp3)-H bonds is often a nontrivial, if not impossible task. Herein we show that leveraging the reactivity of benzylic C(sp3)-H bonds to achieve reactivity at the homobenzylic position can be accomplished using dual organic photoredox/cobalt catalysis. Through a two-part catalytic system, alkyl arenes undergo dehydrogenation followed by an anti-Markovnikov Wacker-type oxidation to grant benzyl ketone products. This formal homobenzylic oxidation is accomplished with high atom economy without the use of directing groups, achieving valuable reactivity that traditionally would require multiple chemical transformations.
A scaffold replacement approach towards new sirtuin 2 inhibitors
Seifert, Tina,Malo, Marcus,Kokkola, Tarja,Stéen, E. Johanna L.,Meinander, Kristian,Wallén, Erik A.A.,Jarho, Elina M.,Luthman, Kristina
, (2019/12/24)
Sirtuins (SIRT1–SIRT7) are an evolutionary conserved family of NAD+-dependent protein deacylases regulating the acylation state of ε-N-lysine residues of proteins thereby controlling key biological processes. Numerous studies have found association of the aberrant enzymatic activity of SIRTs with various diseases like diabetes, cancer and neurodegenerative disorders. Previously, we have shown that substituted 2-alkyl-chroman-4-one/chromone derivatives can serve as selective inhibitors of SIRT2 possessing an antiproliferative effect in two human cancer cell lines. In this study, we have explored the bioisosteric replacement of the chroman-4-one/chromone core structure with different less lipophilic bicyclic scaffolds to overcome problems associated to poor physiochemical properties due to a highly lipophilic substitution pattern required for achieve a good inhibitory effect. Various new derivatives based on the quinolin-4(1H)-one scaffold, bicyclic secondary sulfonamides or saccharins were synthesized and evaluated for their SIRT inhibitory effect. Among the evaluated scaffolds, the benzothiadiazine-1,1-dioxide-based compounds showed the highest SIRT2 inhibitory activity. Molecular modeling studies gave insight into the binding mode of the new scaffold-replacement analogues.
Donor-Acceptor-Acceptor 1,3-Bisdiazo Compounds: An Exploration of Synthesis and Stepwise Reactivity
Abrams, Dylan J.,Davies, Huw M. L.,Sorensen, Erik J.
supporting information, p. 1791 - 1795 (2020/03/24)
Metal carbenes, derived from the decomposition of diazo compounds, are valued for their capacity to perform a variety of transformations. A unique class of acyclic, bis-diazo compounds, the donor-acceptor-acceptor 1,3-bisdiazo compounds, are described her
Discovery of [1,2,4]-triazolo [1,5-a]pyrimidine-7(4H)-one derivatives as positive modulators of GABAA1 receptor with potent anticonvulsant activity and low toxicity
Huang, Longjiang,Ding, Jing,Li, Min,Hou, Zhipeng,Geng, Yanru,Li, Xiufen,Yu, Haibo
, (2019/11/26)
In searching for more effective and safer antiepileptic drugs, a series of 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine-7(4H)-one derivatives were designed and synthesized. Spontaneous Ca2+ oscillations (SCOs) of cortical neurons were used for in vitro phenotypic screening. Maximal electroshock test (MES) and pentylenetetrazole (PTZ) test were used to access their anticonvulsant activity, and rotarod test was used to estimate their neurotoxicity. The active compounds in in vitro model are specifically effective in pentylenetetrazole (PTZ)-induced epilepsy model but not maximal electroshock (MES) model, more importantly with lower neurotoxicity as compared to commonly used drugs. Among them, compound 5c and 5e showed significant anticonvulsant activities in PTZ-induced epilepsy model with ED50 values at 31.81 mg/kg and 40.95 mg/kg, respectively. These compounds have improved neurotoxicity with protective index (PI = TD50/ED50) values at 17.22 and 9.09, respectively. Finally we demonstrated that compound 5c and 5e mainly acted on GABAA receptor as positive modulators but not sodium channels. Thus the present study has provided potential candidates for further investigation in epilepsy.
TBHP/AIBN-Mediated Synthesis of 2-Amino-thioazoles from Active Methylene Ketones and Thiourea under Metal-free Conditions
Sun, Jiyun,Ge, Huaibin,Zhen, Xiaohua,An, Xuechan,Zhang, Guangtao,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
, p. 2107 - 2114 (2018/03/26)
A new oxidative system of tert-butyl hydroperoxide (TBHP)/azodiisobutyronitrile (AIBN) has been used for the first time for a convenient, metal-free synthesis of substituted 2-aminothioazoles from active methylene ketone derivatives and thiourea. The reaction is postulated to proceed via an oxidative cyclization initiated by a radical process and followed by a condensation reaction.
Replacement of the Benzylpiperidine Moiety with Fluorinated Phenylalkyl Side Chains for the Development of GluN2B Receptor Ligands
Thum, Simone,Schepmann, Dirk,Kalinin, Dmitrii V.,Ametamey, Simon M.,Wünsch, Bernhard
, p. 2522 - 2529 (2018/11/23)
The 4-benzylpiperidine moiety is a central structural element of potent N-methyl-d-aspartate (NMDA) receptor antagonists containing the GluN2B subunit. To obtain novel GluN2B ligands suitable for positron emission tomography, the benzylpiperidine moiety was replaced with fluorinated ω-phenylalkylamino groups. For this purpose three primary propyl- and butylamines 7 a–c and one butyraldehyde 7 d bearing a fluorine atom and an ω-phenyl moiety were prepared in 3- to 7-step syntheses. Compounds 7 a–d were attached to various scaffolds of potent GluN2B antagonists (scaffold hopping) instead of the original 4-benzylpiperidine moiety. Although benzoxazol-2-ones and indoles with a benzylpiperidine moiety show high GluN2B affinity, the corresponding fluorophenylalkylamine derivatives did not result in high Glu2B affinity. Moderate GluN2B affinity was observed for a 3-(fluoroalkyl)-substituted tetrahydro-1H-3-benzazepine (Ki=239 nm). However, high GluN2B affinity was obtained for the tetrahydro-5H-benzo[7]annulen-7-amines 12 a–c (Ki=17–30 nm). Docking studies resulted in the same binding pose for 12 a as for the lead compound Ro 25-6981. It can be concluded that some GluN2B ligands (benzoxazolones, indoles) do not tolerate replacement of the 4-benzylpiperidine moiety with flexible fluorinated phenylalkyl side chains, but other scaffolds such as tetrahydro-3-benzazepines and -benzo[7]annulenes retain interaction with NMDA receptors containing the GluN2B subunit.
Oxa-Pictet–Spengler reaction as key step in the synthesis of novel σ receptor ligands with 2-benzopyran structure
Knappmann, Inga,Schepmann, Dirk,Wünsch, Bernhard
, p. 4045 - 4055 (2016/08/23)
The Oxa-Pictet–Spengler reaction of methyl 3-hydroxy-4-phenylbutanoate (8) was explored to obtain novel σ receptor ligands. 1-Acyl protected piperidone ketals 10 and 11 reacted with phenylethanol 8 to yield spirocyclic compounds. Aliphatic aldehyde acetals 19 provided 1,3-disubstituted 2-benzopyrans 20 with high cis-diastereoselectivity. The intramolecular Oxa-Pictet–Spengler reaction of 24 led to the tricyclic compound 25. The spirocyclic compounds 18 show high σ1affinity (Ki20–26?nM) and σ1/σ2selectivity (>9-fold), when a large substituent (n-octyl, benzyl, phenylpropyl) is attached to the piperidine N-atom. Opening of the piperidine ring to yield aminoethyl (22, 23) or aminomethyl derivatives (21) resulted in reduced σ1affinity and σ1/σ2selectivity.
Hauser-Heck: Efficient Synthesis of γ-Aryl-β-ketoesters en Route to Substituted Naphthalenes
Wagner, Frederic,Harms, Klaus,Koert, Ulrich
, p. 5670 - 5673 (2015/12/08)
γ-Aryl-β-ketoesters can be prepared in one step from aryl bromides and bis(trimethylsilyl) enol ethers using catalytic amounts of Pd(dba)2/t-Bu3P and stoichiometric amounts of Bu3SnF. The wide range of γ-(hetero)aryl-β-ketoesters that can be obtained illustrate the scope and limitations of this novel Hauser-Heck combination. γ-Aryl-β-ketoesters with a 1,3-dioxane acetal in the ortho position can easily be transformed into the hydroxy naphthoate in very good yield. Aqueous formic acid at 65 °C provides optimal conditions for this deprotective aromatization.
Total synthesis of (-)-ophiodilactone A and (-)-ophiodilactone B
Matsubara, Takaaki,Takahashi, Keisuke,Ishihara, Jun,Hatakeyama, Susumi
supporting information, p. 757 - 760 (2014/01/23)
The first asymmetric total synthesis of (-)-ophiodilactone A and (-)-ophiodilactone B, isolated from the ophiuroid (Ophiocoma scolopendrina), is reported. The key features of the synthesis include the highly stereocontrolled construction of the structurally congested γ-lactone/δ-lactone skeleton through an asymmetric epoxidation, diastereoselective iodolactonization, and intramolecular epoxide-opening with a carboxylic acid, and biomimetic radical cyclization of ophiodilactone A to ophiodilactone B. Bioinspired synthesis: The first total synthesis of the title compounds has been accomplished in a highly stereocontrolled manner. Key features of the synthesis include an asymmetric epoxidation, a diastereoselective iodolactonization, an intramolecular epoxide opening with a carboxylic acid, and a biomimetic radical cyclization of ophiodilactone A to ophiodilactone B. Copyright
