110874-83-4Relevant articles and documents
The Discovery of (S)-1-(6-(3-((4-(1-(Cyclopropanecarbonyl)piperidin-4-yl)-2-methylphenyl)amino)-2,3-dihydro-1 H -inden-4-yl)pyridin-2-yl)-5-methyl-1 H -pyrazole-4-carboxylic Acid, a Soluble Guanylate Cyclase Activator Specifically Designed for Topical Ocular Delivery as a Therapy for Glaucoma
Ehara, Takeru,Adams, Christopher M.,Bevan, Doug,Ji, Nan,Meredith, Erik L.,Belanger, David B.,Powers, James,Kato, Mitsunori,Solovay, Catherine,Liu, Donglei,Capparelli, Michael,Bolduc, Philippe,Grob, Jonathan E.,Daniels, Matthew H.,Ferrara, Luciana,Yang, Louis,Li, Byron,Towler, Christopher S.,Stacy, Rebecca C.,Prasanna, Ganesh,Mogi, Muneto
, p. 2552 - 2570 (2018/03/26)
Soluble guanylate cyclase (sGC), the endogenous receptor for nitric oxide (NO), has been implicated in several diseases associated with oxidative stress. In a pathological oxidative environment, the heme group of sGC can be oxidized becoming unresponsive to NO leading to a loss in the ability to catalyze the production of cGMP. Recently a dysfunctional sGC/NO/cGMP pathway has been implicated in contributing to elevated intraocular pressure associated with glaucoma. Herein we describe the discovery of molecules specifically designed for topical ocular administration, which can activate oxidized sGC restoring the ability to catalyze the production of cGMP. These efforts culminated in the identification of compound (+)-23, which robustly lowers intraocular pressure in a cynomolgus model of elevated intraocular pressure over 24 h after a single topical ocular drop and has been selected for clinical evaluation.
Rh2(II)-catalyzed ester migration to afford 3 H-indoles from trisubstituted styryl azides
Kong, Chen,Driver, Tom G.
supporting information, p. 802 - 805 (2015/04/27)
Rh2(II)-Complexes trigger the formation of 3H-indoles from ortho-alkenyl substituted aryl azides. This reaction occurs through a 4π-electron-5-atom electrocyclization of the rhodium N-aryl nitrene followed by a [1,2]-migration to afford only 3H-indoles. The selectivity of the migration is dependent on the identity of the β-styryl substituent.