40541-76-2Relevant academic research and scientific papers
Evaluation of the first cytostatically active 1-aza-9-oxafluorenes as novel selective CDK1 inhibitors with P-glycoprotein modulating properties
Brachwitz, Kristin,Voigt, Burkhardt,Meijer, Laurent,Lozach, Olivier,Sch?chtele, Christoph,Molnár, Josef,Hilgeroth, Andreas
, p. 876 - 879 (2003)
The first series of synthetic 1-aza-9-oxafluorenes with cytostatic activities in the micromolar range was evaluated as cyclin-dependent kinase (CDK1) inhibitors. Activity was found to be selective in comparison to the inhibition of other kinases within th
Design, synthesis, and structure-activity relationships of 3,4,5-trisubstituted 4,5-dihydro-1,2,4-oxadiazoles as TGR5 agonists
Zhu, Junjie,Ye, Yangliang,Ning, Mengmeng,Mandi, Attila,Feng, Ying,Zou, Qingan,Kurtan, Tibor,Leng, Ying,Shen, Jianhua
supporting information, p. 1210 - 1223 (2013/07/26)
Given its role in the mediation of energy and glucose homeostasis, the G-protein-coupled bile acid receptor1 (TGR5) is considered a potential target for the treatment of type2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand-based pharmacophore model was built, and a new class of potent TGR5 agonists, based on the novel 3,4,5-trisubstituted 4,5-dihydro-1,2,4-oxadiazole core, was discovered by rational design. Three distinct synthetic methods for constructing 4,5-dihydro-1,2,4-oxadiazoles and extensive structure-activity relationship studies are reported herein. Compound (R)-54n, the structure of which was determined by single-crystal X-ray diffraction and quantum chemical solid-state TDDFT-ECD calculations, showed the best potency, with an EC50 value of 1.4nM toward hTGR5. Its favorable properties invitro warrant further investigation.
Design, synthesis and biological evaluation of a novel class of potent TGR5 agonists based on a 4-phenyl pyridine scaffold
Zhu, Junjie,Ning, Mengmeng,Guo, Cen,Zhang, Lina,Pan, Guoyu,Leng, Ying,Shen, Jianhua
, p. 55 - 68 (2013/10/01)
TGR5, a GPCR, is involved in energy and glucose homeostasis, and as such, is a target for the treatment of diabetes, obesity and other metabolic syndromes. A new class of TGR5 agonists based on a 4-phenyl pyridine scaffold was designed, synthesized and evaluated in vitro and in vivo. Extensive structure-activity relationship studies are reported herein. The most potent compounds 15a, 18b and 18c showed comparable activity with the lead compound 2. 15a had the best potency in vitro but displayed an unfavorable pharmacokinetic profile and was found to be ineffective during an oral glucose tolerance test in imprinting control region mice at a dose of 50 mg/kg.
First rotameric anti dimers and 3,9-diazatetraasteranes from unsymmetrically substituted N-acyl- and N-acyloxy-4-aryl-1,4- dihydropyridines
Hilgeroth, Andreas,Heinemann, Frank W.,Baumeister, Ute
, p. 1003 - 1016 (2007/10/03)
A series of unsymmetrically substituted N-acyl- and N-acyloxy-1,4-dihydropyridines (1) have been photochemically investigated. On irradiating the crystals of one derivative (1a) containing centrosymmetrical pairs of molecules with a distance of 3.894(3) A between the potentially reacting double bonds favorable for a photodimerisation reaction, the formation of an anti-dimer (2a) was observed. Two other solid derivatives (1b, c) merely decomposed on irradiation to give substituted pyridine compound (3). Solution irradiation of 1,4-dihydropyridines (1) led to the centrosymmetric cage compounds 3,9-diazatetraasteranes (4) and to anti dimers (2) as main products, both existing as rotamers. Symmetric as well as rotameric properties of selected compounds (4) have been demonstrated by X-Ray crystal structure analysis and 1H NMR spectroscopy.
Observations on the DDQ oxidation of 1-acyldihydropyridines - A synthetic application
Wallace,Gibb,Cottrell,Kennedy,Brands,Dolling
, p. 1784 - 1789 (2007/10/03)
A synthetic application of the rate difference in oxidation of regioisomerically substituted N-acyldihydropyridines is reported. This has allowed for isolation of pure 4-substituted pyridine isomers without the need for chromatography. Diels-Alder adducts between a dihydropyridine and DDQ were isolated and formation of novel hydroquinone ethers was also observed during some reactions.
Regioselective formation of novel functionalized 1-aza-9-oxafluorenes
Hilgeroth, Andreas,Brachwitz, Kristin,Baumeister, Ute
, p. 661 - 669 (2007/10/03)
A small series of novel 1-aza-9-oxafluorenes have been prepared by regioselective cycloaddition reaction of p-benzoquinone to the sterically unhindered side of unsymmetrically substituted N-acyl-1,4-dihydropyridines (1). The stereochemistry of the product
Identification and characterization of m1 selective muscarinic receptor antagonists1
Augelli-Szafran, Corinne E.,Blankley, C. John,Jaen, Juan C.,Moreland, David W.,Nelson, Carrie B.,Penvose-Yi, Jan R.,Schwarz, Roy D.,Thomas, Anthony J.
, p. 356 - 363 (2007/10/03)
A series of esters of 1,4-disubstituted tetrahydropyridine carboxylic acids (I) has been synthesized and characterized as potential ml selective muscarinic receptor antagonists. The affinity of these compounds for the five human muscarinic receptor subtyp
Aza-Wittig reaction of N-vinylic phosphazenes with carbonyl compounds. Azadiene-mediated synthesis of dihydropyridines and pyridines
Palacios, Francisco,Rubiales, Gloria
, p. 6379 - 6382 (2007/10/03)
Aza-Wittig reaction of N-vinylic phosphazenes derived from diphenylmethylphosphine 4 with carbonyl compounds leads to the formation of 2-azadienes derived from β-aminoacids 5. Dimerization of 2-azadienes 5c,d and reaction of compounds 5 with phosphazene 4 or enemine 6 affords substituted dihydropyridines 7 and 8. Aza-Wittig reaction of phosphazenes 4 with α,β-unsaturated aldehydes gives 3-azatrienes 12, which are easily converted into pyridines 13.
