atrasentan   

GtoPdb Ligand ID: 3487

Synonyms: A-127722 | A-147627 | ABT-627
Compound class: Synthetic organic
Comment: Atrasentan is an orally available, nonpeptide endothelin antagonist. The stereochemistry represented here matches that defined in the INN record for atrasentan.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 13
Topological polar surface area 88.54
Molecular weight 510.27
XLogP 4.23
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Canonical SMILES CCCCN(C(=O)CN1CC(C(C1c1ccc(cc1)OC)C(=O)O)c1ccc2c(c1)OCO2)CCCC
Isomeric SMILES CCCCN(C(=O)CN1C[C@@H]([C@H]([C@@H]1c1ccc(cc1)OC)C(=O)O)c1ccc2c(c1)OCO2)CCCC
InChI InChI=1S/C29H38N2O6/c1-4-6-14-30(15-7-5-2)26(32)18-31-17-23(21-10-13-24-25(16-21)37-19-36-24)27(29(33)34)28(31)20-8-11-22(35-3)12-9-20/h8-13,16,23,27-28H,4-7,14-15,17-19H2,1-3H3,(H,33,34)/t23-,27-,28+/m1/s1
InChI Key MOTJMGVDPWRKOC-QPVYNBJUSA-N
References
1. Chiappori AA, Haura E, Rodriguez FA, Boulware D, Kapoor R, Neuger AM, Lush R, Padilla B, Burton M, Williams C et al.. (2008)
Phase I/II study of atrasentan, an endothelin A receptor antagonist, in combination with paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer.
Clin. Cancer Res., 14 (5): 1464-9. [PMID:18316570]
2. Nelson JB, Chan-Tack K, Hedican SP, Magnuson SR, Opgenorth TJ, Bova GS, Simons JW. (1996)
Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer.
Cancer Res., 56 (4): 663-8. [PMID:8630991]
3. Opgenorth TJ, Adler AL, Calzadilla SV, Chiou WJ, Dayton BD, Dixon DB, Gehrke LJ, Hernandez L, Magnuson SR, Marsh KC et al.. (1996)
Pharmacological characterization of A-127722: an orally active and highly potent ETA-selective receptor antagonist.
J. Pharmacol. Exp. Ther., 276 (2): 473-81. [PMID:8632312]
4. Salani D, Rosanò L, Di Castro V, Spinella F, Venuti A, Padley RJ, Nicotra MR, Natali PG, Bagnato A. (2002)
ABT-627, a potent endothelin receptor A antagonist, inhibits ovarian carcinoma growth in vitro.
Clin. Sci., 103 Suppl 48: 318S-321S. [PMID:12193113]
5. Sasser JM, Sullivan JC, Hobbs JL, Yamamoto T, Pollock DM, Carmines PK, Pollock JS. (2007)
Endothelin A receptor blockade reduces diabetic renal injury via an anti-inflammatory mechanism.
J. Am. Soc. Nephrol., 18 (1): 143-54. [PMID:17167119]
6. Winn M, von Geldern TW, Opgenorth TJ, Jae HS, Tasker AS, Boyd SA, Kester JA, Mantei RA, Bal R, Sorensen BK et al.. (1996)
2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
J. Med. Chem., 39 (5): 1039-48. [PMID:8676339]