netarsudil   

GtoPdb Ligand ID: 9322

Synonyms: AR-11324 | AR11324 | ester 60 [PMID: 27072905] | Rhokiinsa® | Rhopressa®
netarsudil is an approved drug (FDA (2017), EMA (2019))
Compound class: Synthetic organic
Comment: Netarsudil (AR-11324) is a combination Rho-associated protein kinase (Rho or ROCK) and norepinephrine transporter (NET) inhibitor [2,5]. Netarsudil is the S-enantiomeric, 2,4-dimethyl benzoate ester of compound 29 (Ki 0.2nM) described in [5]. Esterification improves bioavailability and corneal penetrating ability of the compound. It is an ocular hypotensive medication.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 94.31
Molecular weight 453.21
XLogP 4.35
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES NCC(C(=O)Nc1ccc2c(c1)ccnc2)c1ccc(cc1)COC(=O)c1ccc(cc1C)C
Isomeric SMILES NC[C@@H](C(=O)Nc1ccc2c(c1)ccnc2)c1ccc(cc1)COC(=O)c1ccc(cc1C)C
InChI InChI=1S/C28H27N3O3/c1-18-3-10-25(19(2)13-18)28(33)34-17-20-4-6-21(7-5-20)26(15-29)27(32)31-24-9-8-23-16-30-12-11-22(23)14-24/h3-14,16,26H,15,17,29H2,1-2H3,(H,31,32)/t26-/m1/s1
InChI Key OURRXQUGYQRVML-AREMUKBSSA-N
References
1. Dayal N, Mikek CG, Hernandez D, Naclerio GA, Yin Chu EF, Carter-Cooper BA, Lapidus RG, Sintim HO. (2019)
Potently inhibiting cancer cell migration with novel 3H-pyrazolo[4,3-f]quinoline boronic acid ROCK inhibitors.
Eur J Med Chem, 180: 449-456. DOI: 10.1016/j.ejmech.2019.06.089 [PMID:31330446]
2. Lin CW, Sherman B, Moore LA, Laethem CL, Lu DW, Pattabiraman PP, Rao PV, deLong MA, Kopczynski CC. (2018)
Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma.
J Ocul Pharmacol Ther, 34 (1-2): 40-51. [PMID:28609185]
3. Ren R, Li G, Le TD, Kopczynski C, Stamer WD, Gong H. (2016)
Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms.
Invest. Ophthalmol. Vis. Sci., 57 (14): 6197-6209. [PMID:27842161]
4. Serle JB, Katz LJ, McLaurin E, Heah T, Ramirez-Davis N, Usner DW, Novack GD, Kopczynski CC, ROCKET-1 and ROCKET-2 Study Groups. (2018)
Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).
Am. J. Ophthalmol., 186: 116-127. [PMID:29199013]
5. Sturdivant JM, Royalty SM, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong MA. (2016)
Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma.
Bioorg. Med. Chem. Lett., 26 (10): 2475-80. [PMID:27072905]