218430-47-8Relevant academic research and scientific papers
Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design
Dong, Xiaowu,Zhan, Wenhu,Zhao, Mengting,Che, Jinxin,Dai, Xiaoyang,Wu, Yizhe,Xu, Lei,Zhou, Yubo,Zhao, Yanmei,Tian, Tian,Cheng, Gang,Jin, Zegao,Li, Jia,Shao, Yanfei,He, Qiaojun,Yang, Bo,Weng, Qinjie,Hu, Yongzhou
, p. 7264 - 7288 (2019/08/20)
A series of 3,4-disubstituted piperidine derivatives were obtained based on a conformational restriction strategy and a lead compound, A12, that exhibited potent in vitro and in vivo antitumor efficacies; however, obvious safety issues limited its further development. Thus, systematic exploration of the structure-activity relationship of compound A12, involving the phenyl group, hinge-linkage, and piperidine moiety, led to the discovery of the superior 3,4,6-trisubstituted piperidine derivative E22. E22 showed increased potency in Akt1 and cancer cell inhibition, remarkably reduced human ether-a-go-go-related gene blockage, and significantly improved safety profiles. Compound E22 also exhibited good kinase selectivity, had a good pharmacokinetic profile, and displayed very potent in vivo antitumor efficacy, with over 90% tumor growth inhibition in the SKOV3 xenograft model. Further mechanistic studies were conducted to demonstrate that compound E22 could significantly inhibit the phosphorylation of proteins downstream of Akt kinase in cells and tumor tissue from the xenograft model.
Functionalized β-cyclodextrin as supramolecular ligand and their Pd(OAc)2 complex: Highly efficient and reusable catalyst for Mizoroki-Heck cross-coupling reactions in aqueous medium
Dindulkar, Someshwar D.,Jeong, Daham,Kim, Hwanhee,Jung, Seunho
, p. 85 - 94 (2016/06/01)
A novel class of water soluble palladium complexes with recognition abilities based on functionalized β-cyclodextrin has been synthesized. The complex demonstrated high catalytic activity and a supramolecular platform for phosphine-free Mizoroki-Heck cross-coupling reactions in water. The efficient arylation of alkenes was carried out using different iodo- and bromo-arenes with good to excellent yields (up to 96%). The advantages, like recyclability of catalysts, operational simplicity and accessibility in aqueous medium, make this protocol eco-friendly.
Catechol-based substrates of chalcone synthase as a scaffold for novel inhibitors of PqsD
Allegretta, Giuseppe,Weidel, Elisabeth,Empting, Martin,Hartmann, Rolf W.
, p. 351 - 359 (2015/02/19)
A new strategy for treating Pseudomonas aeruginosa infections could be disrupting the Pseudomonas Quinolone Signal (PQS) quorum sensing (QS) system. The goal is to impair communication among the cells and, hence, reduce the expression of virulence factors and the formation of biofilms. PqsD is an essential enzyme for the synthesis of PQS and shares some features with chalcone synthase (CHS2), an enzyme expressed in Medicago sativa. Both proteins are quite similar concerning the size of the active site, the catalytic residues and the electrostatic surface potential at the entrance of the substrate tunnel. Hence, we evaluated selected substrates of the vegetable enzyme as potential inhibitors of the bacterial protein. This similarity-guided approach led to the identification of a new class of PqsD inhibitors having a catechol structure as an essential feature for activity, a saturated linker with two or more carbons and an ester moiety bearing bulky substituents. The developed compounds showed PqsD inhibition with IC50 values in the single-digit micromolar range. The binding mode of these compounds was investigated by Surface Plasmon Resonance (SPR) experiments revealing that their interaction with the protein is not influenced by the presence of the anthranilic acid bound to active site cysteine. Importantly, some compounds reduced the signal molecule production in cellulo.
SYNTHESIS OF 2-(3,4-DIFLUOROPHENYL)CYCLOPROPANAMINE DERIVATIVES AND SALTS
-
Page/Page column 16, (2013/10/21)
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor.
Synthesis of 2-(3,4-difluorophenyl)cyclopropanamine derivatives and salts
-
Paragraph 0053, (2013/10/21)
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor.
Modifying the acylation of flavonols in Petunia hybrida
Cunningham, Oliver D.,Edwards, Robert
, p. 2016 - 2021 (2008/12/22)
The potential for chemically-regulating the acylation of natural products in whole plants has been determined by treating petunia leaves with phenylpropanoid acyl donors supplied as the respective methyl esters. Treatment with derivatives of the naturally-occurring acylating species caffeic acid resulted in a general increase in flavonol derivatives, notably caffeoylated quercetin-3-O-diglucoside (QDG) and kaempferol-3-O-diglucoside (KDG). Similarly, methyl ferulate increased the content of feruloylated KDG 40-fold. Treatment with methyl coumarate resulted in the appearance of a coumaroylated derivative of quercetin-3-O-glucuronyl-glucoside (QGGA). When the feeding studies were repeated with the equivalent phenylpropanoid isosubstituted with fluorine groups a semi-synthetic 4-fluorocinnamoyl ester of QGGA was observed. Our results demonstrate the potential to regulate the acylation of flavonols and potentially other natural products by treating whole plants with methyl esters of natural and unnatural acyl donors.
Design and synthesis of highly potent benzodiazepine γ-secretase inhibitors: Preparation of (2S,3R)-3-(3,4- difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-1-methyl-2-oxo-5- phenyl-2,3-dihydro-1H-benzo[e][1,4]-diazepin-3-yl)butyramide by use of an as
Churcher, Ian,Williams, Susie,Kerrad, Sonia,Harrison, Timothy,Castro, José L.,Shearman, Mark S.,Lewis, Huw D.,Clarke, Earl E.,Wrigley, Jonathan D. J.,Beher, Dirk,Tang, Yui S.,Liu, Wensheng
, p. 2275 - 2278 (2007/10/03)
Novel benzodiazepine-containing γ-secretase inhibitors for potential use in Alzheimer's disease have been designed that incorporate a substituted hydrocinnamide C-3 side chain. A syn combination of α-alkyl or aryl and β-hydroxy or hydroxymethyl substituen
Oxazolidinones useful as alpha 1A adrenoceptor antagonists
-
, (2008/06/13)
Novel oxazolidinone compounds and pharmaceutically acceptable salts thereof are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.
Oxazolidinones useful as alpha 1a adrenoceptor antagonists
-
, (2008/06/13)
Novel hydroxymethyl- and alkoxymethyl-oxazolidinone compounds and pharmaceutically acceptable salts thereof are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.
Alpha 1a adrenergic receptor antagonists
-
, (2008/06/13)
This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.
