naldemedine   

GtoPdb Ligand ID: 9150

Synonyms: compound 9k [PMID: 30446313] | S-297,995 | S-297995
naldemedine is an approved drug (FDA (2017), EMA (2019))
Compound class: Synthetic organic
Comment: Naldemedine (S-297995) is a dual μ/δ opioid receptor antagonist, designed to act peripherally (peripherally acting mu-opioid receptor antagonist or PAMORA) [1]. It is used clinically for its ability to counteract opioid agonist-induced adverse effects such as constipation, nausea, and vomiting. Naldemedine was developed by Shionogi Inc. It is the compound claimed in patent WO2013172297 with formula IA (17-(cyclopropylmethyl)-6,7-didehydro-4,5α-epoxy-3,6,14-trihydroxy-N-[2-(3-phenyl-1,2,4-oxadiazol-5-yl)propan-2-yl]morphinan-7-carboxamide 4-methylbenzenesulfonic acid) [2].
2D Structure
Click here for structure editor
Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 4
Rotatable bonds 7
Topological polar surface area 141.18
Molecular weight 570.25
XLogP 3.31
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES O=C(C1=C(O)C2C34C(C1)(O)C(Cc1c4c(O2)c(O)cc1)N(CC3)CC1CC1)NC(c1onc(n1)c1ccccc1)(C)C
Isomeric SMILES O=C(C1=C(O)[C@H]2[C@]34[C@](C1)(O)[C@@H](Cc1c4c(O2)c(O)cc1)N(CC3)CC1CC1)NC(c1onc(n1)c1ccccc1)(C)C
InChI InChI=1S/C32H34N4O6/c1-30(2,29-33-27(35-42-29)18-6-4-3-5-7-18)34-28(39)20-15-32(40)22-14-19-10-11-21(37)25-23(19)31(32,26(41-25)24(20)38)12-13-36(22)16-17-8-9-17/h3-7,10-11,17,22,26,37-38,40H,8-9,12-16H2,1-2H3,(H,34,39)/t22-,26+,31+,32-/m1/s1
InChI Key AXQACEQYCPKDMV-RZAWKFBISA-N
References
1. Inagaki M, Kume M, Tamura Y, Hara S, Goto Y, Haga N, Hasegawa T, Nakamura T, Koike K, Oonishi S et al.. (2019)
Discovery of naldemedine: A potent and orally available opioid receptor antagonist for treatment of opioid-induced adverse effects.
Bioorg. Med. Chem. Lett., 29 (1): 73-77. [PMID:30446313]
2. Mashimo A, Ichiio S. (2013)
Preparation containing 6,7-unsaturated-7-carbamoylmorphinan derivative.
Patent number: WO2013172297 A1. Assignee: Shionogi & Co., Ltd. Priority date: 14/05/2012. Publication date: 21/11/2013.