587-11-1Relevant academic research and scientific papers
Aryloxycyclohexyl amide AMPK agonist as well as preparation method and medical application thereof
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Paragraph 0049; 0054-0055; 0228; 0230-0232, (2022/04/06)
The invention discloses an aryloxy cyclohexyl amide AMPK agonist as well as a preparation method and medical application thereof. The AMPK agonist is specifically an aryloxy cyclohexyl amide compound as shown in a formula (I) or pharmaceutically acceptable salt or ester or solvate of the aryloxy cyclohexyl amide compound. The aryloxy cyclohexyl amide compound with the AMPK agonistic activity has remarkable agonistic activity on AMPK at the cellular level, and can effectively activate an AMPK signal channel in vivo, so that the aryloxy cyclohexyl amide compound can be used for preparing medicines for preventing or treating various AMPK-mediated diseases.
Exploration of a 14-3-3 PPI Pocket by Covalent Fragments as Stabilizers
Sijbesma, Eline,Hallenbeck, Kenneth K.,Andrei, Sebastian A.,Rust, Reanne R.,Adriaans, Joris M. C.,Brunsveld, Luc,Arkin, Michelle R.,Ottmann, Christian
, p. 976 - 982 (2021/05/27)
The systematic discovery of functional fragments binding to the composite interface of protein complexes is a first critical step for the development of orthosteric stabilizers of protein-protein interactions (PPIs). We have previously shown that disulfide trapping successfully yielded covalent stabilizers for the PPI of 14-3-3 with the estrogen receptor ERα. Here we provide an assessment of the composite PPI target pocket and the molecular characteristics of various fragments binding to a specific subpocket. Evaluating structure-activity relationships highlights the basic principles for PPI stabilization by these covalent fragments that engage a relatively large and exposed binding pocket at the protein/peptide interface with a "molecular glue"mode of action.
Design, synthesis of novel, potent, selective, orally bioavailable adenosine A2A receptor antagonists and their biological evaluation
Basu, Sujay,Barawkar, Dinesh A.,Thorat, Sachin,Shejul, Yogesh D.,Patel, Meena,Naykodi, Minakshi,Jain, Vaibhav,Salve, Yogesh,Prasad, Vandna,Chaudhary, Sumit,Ghosh, Indraneel,Bhat, Ganesh,Quraishi, Azfar,Patil, Harish,Ansari, Shariq,Menon, Suraj,Unadkat, Vishal,Thakare, Rhishikesh,Seervi, Madhav S.,Meru, Ashwinkumar V.,De, Siddhartha,Bhamidipati, Ravi K.,Rouduri, Sreekanth R.,Palle, Venkata P.,Chug, Anita,Mookhtiar, Kasim A.
, p. 681 - 694 (2017/02/05)
Our initial structure-activity relationship studies on 7-methoxy-4-morpholino-benzothiazole derivatives featured by aryloxy-2-methylpropanamide moieties at the 2-position led to identification of compound 25 as a potent and selective A2A adenosine receptor (A2AAdoR) antagonist with reasonable ADME and pharmacokinetic properties. However, poor intrinsic solubility and low to moderate oral bioavailability made this series unsuitable for further development. Further optimization using structure-based drug design approach resulted in discovery of potent and selective adenosine A2A receptor antagonists bearing substituted 1-methylcyclohexyl-carboxamide groups at position 2 of the benzothiazole scaffold and endowed with better solubility and oral bioavailability. Compounds 41 and 49 demonstrated a number of positive attributes with respect to in vitro ADME properties. Both compounds displayed good pharmacokinetic properties with 63% and 61% oral bioavailability, respectively, in rat. Further, compound 49 displayed oral efficacy in 6-OHDA lesioned rat model of Parkinson diseases.
Pd(II)-catalyzed ortho - Or meta-C-H olefination of phenol derivatives
Dai, Hui-Xiong,Li, Gang,Zhang, Xing-Guo,Stepan, Antonia F.,Yu, Jin-Quan
supporting information, p. 7567 - 7571 (2013/06/27)
A combination of weakly coordinating auxiliaries and ligand acceleration allows for the development of both ortho- and meta-selective C-H olefination of phenol derivatives. These reactions demonstrate the feasibility of directing C-H functionalizations when functional groups are distal to target C-H bonds. The meta-C-H functionalization of electron-rich phenol derivatives is unprecedented and orthogonal to previous electrophilic substitution of phenols in terms of regioselectivity. These methods are also applied to functionalize α-phenoxyacetic acids, a fibrate class of drug scaffolds.
Synthesis and preliminary antihyperlipidaemic activities evaluation of andrographolide derivatives
Wang, Bin,Tang, Chunlei,Han, Yaodan,Guo, Ruzhou,Qian, Hai,Huang, Wenlong
experimental part, p. 293 - 298 (2012/07/30)
Recent studies indicated that andrographolide was a potential antihyperlipidaemic therapeutic agent. In the paper, the synthesis of a series of andrographolide derivatives was described and their antihyperlipidaemic activities were evaluated in vivo. As compared with TG, TC, HDL-C and LDL-C concentrations, some of the derivatives exhibited better antihyperlipidaemic effects than positive control atromide. Therein, compound 6i, which was the most potent compound, could serve as a new lead for further development of antihyperlipidaemic agents.
Water-based biphasic media for exothermic reactions: Green chemistry strategy for the large scale preparation of clofibric acid and analogues
Bose, Ajay K.,Manhas, Maghar S.,Ganguly, Subhendu N.,Pednekar, Suhas,Mandadi, Arun
, p. 3011 - 3013 (2007/10/03)
A water-based biphasic reaction process has been developed for conducting exothermic reactions without organic solvents. This procedure is rapid, simple, and suitable for small scale synthesis as well as larger (multi-molar) scale reactions. The preparation of several hundred grams of clofibric acid and analogues by this eco-friendly and energy-efficient procedure is described. Smaller amounts of these compounds were prepared by the friction-activated 'Grindstone Chemistry' method described previously.
A simple synthetic route to 3-phenoxybenzyl 2-methyl-2-(p-substituted phenoxy and thiophenoxy/naphthoxy)propyl ethers, structurally related to ethofenoprox
Kumaran, G.,Kulkarni, G. H.
, p. 168 - 170 (2007/10/02)
Some 3-phenoxybenzyl 2-methyl-2-(p-substituted phenoxy and thiophenoxy/naphthoxy)propyl ethers (8), bearing close structural resemblance to the powerful insecticide MTI-500 have been synthesised by a simple route for evaluating their insecticidal properties.
ipso Nitration in p-halophenyl ethers
Clewley, Robin G.,Fischer, Alfred,Henderson, George N.
, p. 1472 - 1479 (2007/10/02)
Addition of nitronium ion ipso to halogen occurs on nitration of the p-haloanisoles in acetic anhydride at -60 deg C.In the cases of p-fluoro- and p-chloro-anisole, addition of the nitronium ion is reversible and only small amounts of ipso products are obtained.With p-bromoanisole nitrodebromination occurs.When p-halophenyl ethers containing a trapping substituent, e.g., 2-(4-chlorophenoxy)-2-methylpropanoic acid, are used as substrates, substantial amounts of the spiro diene with nitro ipso to halogen, e.g., 3,3-dimethyl-8-chloro-8-nitro-1,4-dioxaspirodeca-6,9-dien-2-one, can be isolated.The results demonstrate that extensive ipso attack at the halogen-substituted position is general in the nitration of p-halophenyl ethers.Key words: ipso nitration, ether, diene, p-haloanisole.
