403672-01-5Relevant articles and documents
TOPS-MODE model of multiplexing neuroprotective effects of drugs and experimental-theoretic study of new 1,3-rasagiline derivatives potentially useful in neurodegenerative diseases
Luan, Feng,Cordeiro, M. Natália D.S.,Alonso, Nerea,García-Mera, Xerardo,Caama?o, Olga,Romero-Duran, Francisco J.,Ya?ez, Matilde,González-Díaz, Humberto
, p. 1870 - 1879 (2013/04/24)
The interest on computational techniques for the discovery of neuroprotective drugs has increased due to recent fail of important clinical trials. In fact, there is a huge amount of data accumulated in public databases like CHEMBL with respect to structurally heterogeneous series of drugs, multiple assays, drug targets, and model organisms. However, there are no reports of multi-target or multiplexing Quantitative Structure-Property Relationships (mt-QSAR/mx-QSAR) models of these multiplexing assay outcomes reported in CHEMBL for neurotoxicity/neuroprotective effects of drugs. Accordingly, in this paper we develop the first mx-QSAR model for multiplexing assays of neurotoxicity/neuroprotective effects of drugs. We used the method TOPS-MODE to calculate the structural parameters of drugs. The best model found correctly classified 4393 out of 4915 total cases in both training and validation. This is representative of overall train and validation Accuracy, Sensitivity, and Specificity values near to 90%, 98%, and 80%, respectively. This dataset includes multiplexing assay endpoints of 2217 compounds. Every one compound was assayed in at least one out of 338 assays, which involved 148 molecular or cellular targets and 35 standard type measures in 11 model organisms (including human). The second aim of this work is the exemplification of the use of the new mx-QSAR model with a practical case of study. To this end, we obtained again by organic synthesis and reported, by the first time, experimental assays of the new 1,3-rasagiline derivatives 3 different tests: assay (1) in absence of neurotoxic agents, (2) in the presence of glutamate, and (3) in the presence of H2O2. The higher neuroprotective effects found for each one of these assays were for the stereoisomers of compound 7: compound 7b with protection = 23.4% in assay (1) and protection = 15.2% in assay (2); and for compound 7a with protection = 46.2% in assay (3). Interestingly, almost all compounds show protection values >10% in assay (3) but not in the other 2 assays. After that, we used the mx-QSAR model to predict the more probable response of the new compounds in 559 unique pharmacological tests not carried out experimentally. The results obtained are very significant because they complement the pharmacological studies of these promising rasagiline derivatives. This work paves the way for further developments in the multi-target/multiplexing screening of large libraries of compounds potentially useful in the treatment of neurodegenerative diseases.
Highly efficient biocatalytic resolution of cis- and trans-3-aminoindan-1- ol: Syntheses of enantiopure orthogonally protected cis- and trans-indane-1,3-diamine
Lopez-Garcia, Monica,Alfonso, Ignacio,Gotor, Vicente
, p. 3006 - 3014 (2007/10/03)
The efficient chemoenzymatic synthesis of enantiopure 1,3-difunctionalized indane derivatives has been achieved. The corresponding cis and trans N-protected amino alcohols were successfully resolved by acetylation using lipase B, which is a biocatalyst is
Enantiopure trans- and cis-3-Aminoindan-1-ols: Preparation and application as novel basic resolving agents
Kinbara, Kazushi,Katsumata, Yoshiyuki,Saigo, Kazuhiko
, p. 266 - 267 (2007/10/03)
trans- and cis-3-Aminoindan-1-ols were prepared by moderately selective reductions of 3-aminoindan-1-one derivatives and separated into enantiopure forms. The enantiopure trans-isomer had a moderate resolving ability for 2-arylalkanoic acids having a naphthalene ring at the α-position. The X-ray crystallographic analysis showed that an infinite hydrogen-bond sheet was formed in the less-soluble salt, suggesting that the skeleton of these indanols would be favorable for the stabilization of the less-soluble salt by hydrogen-bonding interaction.
3-amino-1-indanole, method of synthesizing the same and method of optical resolution
-
, (2008/06/13)
The present invention relates to a compound which is expected to be a synthetic intermediate for medicines and pesticides or a separating agent for chromatography or a enantiomerically resolving agent for racemic bodies. That is, it provides 3-amino-1-indanol represented by the formula (I), a process for synthesizing it, an enantiomerically active compound of 3-amino-1-indanol and a process for enantiomerically resolving 3-amino-1-indanol, and a separating agent for enantiomeric isomers comprising enantiomerically active compound thereof as an effective ingredient. In the formula, the configuration between OH group and NH2group are cis-configuration or trans-configuration and the compound may be a racemic body or an enantiomerically active compound.
