19962-04-0Relevant articles and documents
HIGHLY CHEMOSELECTIVE REACTIONS IN PRESENCE OF AROMATIC AMINO GROUPS
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Page/Page column 31, (2017/11/06)
: The invention discloses a novel process for highly chemoselective reactions of substituted anilines without any detectable reaction at aromatic amino group. The invention also relates to a novel process for preparation of neostigmine methylsulphate via chemoselective reaction of 3-amionphenol and aryl dimethylcarbamates.
Discovery and development of LX7101, a dual LIM-kinase and ROCK inhibitor for the treatment of glaucoma
Harrison, Bryce A.,Almstead, Zheng Y.,Burgoon, Hugh,Gardyan, Michael,Goodwin, Nicole C.,Healy, Jason,Liu, Ying,Mabon, Ross,Marinelli, Brett,Samala, Lakshman,Zhang, Yulian,Stouch, Terry R.,Whitlock, N. Andrew,Gopinathan, Suma,McKnight, Beth,Wang, Shuli,Patel, Nita,Wilson, Alan G. E.,Hamman, Brian D.,Rice, Dennis S.,Rawlins, David B.
, p. 84 - 88 (2015/01/30)
The structure of LX7101, a dual LIM-kinase and ROCK inhibitor for the treatment of ocular hypertension and associated glaucoma, is disclosed. Previously reported LIM kinase inhibitors suffered from poor aqueous stability due to solvolysis of the central urea. Replacement of the urea with a hindered amide resulted in aqueous stable compounds, and addition of solubilizing groups resulted in a set of compounds with good properties for topical dosing in the eye and good efficacy in a mouse model of ocular hypertension. LX7101 was selected as a clinical candidate from this group based on superior efficacy in lowering intraocular pressure and a good safety profile. LX7101 completed IND enabling studies and was tested in a Phase 1 clinical trial in glaucoma patients, where it showed efficacy in lowering intraocular pressure. (Figure Presented).
Novel class of LIM-kinase 2 inhibitors for the treatment of ocular hypertension and associated glaucoma
Harrison, Bryce A.,Whitlock, N. Andrew,Voronkov, Michael V.,Almstead, Zheng Y.,Gu, Kun-Jian,Mabon, Ross,Gardyan, Michael,Hamman, Brian D.,Allen, Jason,Gopinathan, Suma,McKnight, Beth,Crist, Mike,Zhang, Yulian,Liu, Ying,Courtney, Lawrence F.,Key, Billie,Zhou, Julia,Patel, Nita,Yates, Phil W.,Liu, Qingyun,Wilson, Alan G. E.,Kimball, S. David,Crosson, Craig E.,Rice, Dennis S.,Rawlins, David B.
supporting information; experimental part, p. 6515 - 6518 (2010/03/31)
The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating ocular hypertension and associated glaucoma.
