30084-91-4Relevant articles and documents
Optically Active Spiranes, XI: Syntheses of Optically Active Mono to Heptasubstituted 5-Methyl and Ethyl-2,2'-Spirobiindanes and Related Naphthalene Derivatives of Known Chirality and Enantiomeric Purity
Neudeck, Horst,Schloegl, Karl
, p. 801 - 824 (1981)
Starting from optically active 5,5'-dimethyl, diethyl, and 5-ethyl-5'-methyl-2,2'-spirobiindane as well as from 5'-ethyl-spirobiindane-5-carboxylic ester of known enantiomeric purity and configuration 75 mono to polysubstituted 2,2'-spirobiindanes have been prepared.Amongst these are several compounds with rings anellated in the 6,7 (and 6',7') positions, especially a spirohydrocarbon 4x with orthogonal naphthalene units the circular dichroism of which is reported and discussed.Several mono and disubstituted 5-methyl and ethylindanes (1, 2) have been prepared as models for synthetic transformations in the spirobiindane series.From the molar rotations of symmetrically diacylated 5,5'-dimethyl and diethyl spirobiindanes (4a, 7b, 7c) empirical ligand parameters λ for acetyl and methoxycarbonyl were determined which gave much better results in the calculation of the rotations of appropriate spirobiindanes (with the "shortened polynomal Ansatz") than the λ-values deduced previously from 5,5'-disubstituted spirobiindanes.The significance of these results is briefly discussed. - Keywords: Chirality function; Circular dichroism; Ligand parameters; 5-Methyl and ethylindanes; 1H-NMR spectra
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Arnold
, p. 1405 (1939)
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Computer-Assisted Discovery and Structural Optimization of a Novel Retinoid X Receptor Agonist Chemotype
Heitel, Pascal,Gellrich, Leonie,Kalinowsky, Lena,Heering, Jan,Kaiser, Astrid,Ohrndorf, Julia,Proschak, Ewgenij,Merk, Daniel
supporting information, p. 203 - 208 (2019/01/25)
As universal heterodimer partners of many nuclear receptors, the retinoid X receptors (RXRs) constitute key transcription factors. They regulate cell proliferation, differentiation, inflammation, and metabolic homeostasis and have recently been proposed as potential drug targets for neurodegenerative and inflammatory diseases. Owing to the hydrophobic nature of RXR ligand binding sites, available synthetic RXR ligands are lipophilic, and their structural diversity is limited. Here, we disclose the computer-assisted discovery of a novel RXR agonist chemotype and its systematic optimization toward potent RXR modulators. We have developed a nanomolar RXR agonist with high selectivity among nuclear receptors and superior physicochemical properties compared to classical rexinoids that appears suitable for in vivo applications and as lead for future RXR-targeting medicinal chemistry.
Structure activity relationships of αv integrin antagonists for pulmonary fibrosis by variation in aryl substituents
Adams, James,Anderson, Edward C.,Blackham, Emma E.,Chiu, Yin Wa Ryan,Clarke, Thomas,Eccles, Natasha,Gill, Luke A.,Haye, Joshua J.,Haywood, Harvey T.,Hoenig, Christian R.,Kausas, Marius,Le, Joelle,Russell, Hannah L.,Smedley, Christopher,Tipping, William J.,Tongue, Tom,Wood, Charlotte C.,Yeung, Jason,Rowedder, James E.,Fray, M. Jonathan,McInally, Thomas,Macdonald, Simon J. F.
, p. 1207 - 1212 (2015/04/27)
Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvβ3, αvβ5, αvβ6, and αvβ8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvβ3 and αvβ5.
