1687-64-5Relevant articles and documents
Miller,Stedman
, p. 1135,1137,1140 (1971)
Synthesis of Highly Substituted Phenols and Benzenes with Complete Regiochemical Control
Zhang, Xiaojie,Beaudry, Christopher M.
supporting information, p. 6086 - 6090 (2020/08/12)
Substituted phenols are requisite molecules for human health, agriculture, and diverse synthetic materials. We report a chemical synthesis of phenols, including penta-substituted phenols, that accommodates programmable substitution at any position. This method uses a one-step conversion of readily available hydroxypyrone and nitroalkene starting materials to give phenols with complete regiochemical control and in high chemical yield. Additionally, the phenols can be converted into highly and even fully substituted benzenes.
Novel S1P1 receptor agonists - Part 3: From thiophenes to pyridines
Bolli, Martin H.,Abele, Stefan,Birker, Magdalena,Bravo, Roberto,Bur, Daniel,De Kanter, Ruben,Kohl, Christopher,Grimont, Julien,Hess, Patrick,Lescop, Cyrille,Mathys, Boris,Müller, Claus,Nayler, Oliver,Rey, Markus,Scherz, Michael,Schmidt, Gunther,Seifert, Jürgen,Steiner, Beat,Velker, J?rg,Weller, Thomas
, p. 110 - 130 (2014/02/14)
In preceding communications we summarized our medicinal chemistry efforts leading to the identification of potent, selective, and orally active S1P 1 agonists such as the thiophene derivative 1. As a continuation of these efforts, we replaced the thiophene in 1 by a 2-, 3-, or 4-pyridine and obtained less lipophilic, potent, and selective S1P1 agonists (e.g., 2) efficiently reducing blood lymphocyte count in the rat. Structural features influencing the compounds' receptor affinity profile and pharmacokinetics are discussed. In addition, the ability to penetrate brain tissue has been studied for several compounds. As a typical example for these pyridine based S1P 1 agonists, compound 53 showed EC50 values of 0.6 and 352 nM for the S1P1 and S1P3 receptor, respectively, displayed favorable PK properties, and penetrated well into brain tissue. In the rat, compound 53 maximally reduced the blood lymphocyte count for at least 24 h after oral dosing of 3 mg/kg.
Novel S1P1 receptor agonists - Part 1: From pyrazoles to thiophenes
Bolli, Martin H.,Müller, Claus,Mathys, Boris,Abele, Stefan,Birker, Magdalena,Bravo, Roberto,Bur, Daniel,Hess, Patrick,Kohl, Christopher,Lehmann, David,Nayler, Oliver,Rey, Markus,Meyer, Solange,Scherz, Michael,Schmidt, Gunther,Steiner, Beat,Treiber, Alexander,Velker, J?rg,Weller, Thomas
, p. 9737 - 9755 (2014/01/06)
From a high-throughput screening campaign aiming at the identification of novel S1P1 receptor agonists, the pyrazole derivative 2 emerged as a hit structure. Medicinal chemistry efforts focused not only on improving the potency of the compound but in particular also on resolving its inherent instability issue. This led to the discovery of novel bicyclo[3.1.0]hexane fused thiophene derivatives. Compounds with high affinity and selectivity for S1P1 efficiently reducing the blood lymphocyte count in the rat were identified. For instance, compound 85 showed EC50 values of 7 and 2880 nM on S1P1 and S1P3, respectively, had favorable pharmacokinetic properties in rat and dog, distributed well into brain tissue, and efficiently and dose dependently reduced the blood lymphocyte count in the rat. After oral administration to spontaneously hypertensive rats, the S1P 1 selective compound 85 showed no effect on mean arterial blood pressure and affected the heart rate during the wake phase of the animals only.
