5-Aryluracils as potent GnRH antagonists-Characterization of atropisomers

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 11, 2008, Pages 3344-3349

  Zhao, Liren ^a   Guo, Zhiqiang ^a   Chen, Yongsheng ^a   Hu, Tao ^a   Wu, Dongpei ^a   Zhu, Yun Fei ^a   Rowbottom, Martin ^a   Gross, Timothy D ^a   Tucci, Fabio C ^a   Struthers, R Scott ^a   Xie, Qiu ^a   Chen, Chen ^a  

^a NEUROCRINE BIOSCIENCES INC   (United States)

Author keywords

Atropisomer; Gonadotropin releasing hormone (GnRH); NMR; Receptor; Stereoisomer; Uracil; X ray crystal structure

Indexed keywords

GONADORELIN ANTAGONIST; PHENYL GROUP; URACIL DERIVATIVE;

ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG MECHANISM; DRUG SYNTHESIS; HUMAN; ISOMER;

CRYSTALLOGRAPHY, X-RAY; HUMANS; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; RECEPTORS, LHRH; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; URACIL;

EID: 44149101229     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.04.029     Document Type: Article

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25. Separation was performed on a Beckman 322 semipreparative HPLC equipped with a 10 × 250 nm Chirex 3020AL column at a solvent flow-rate of 0.3 ml/min. Mobile phase A consisted of hexane: 1,2-dichloroethane (65:35) while mobile phase B was composed of hexane:1,2-dichloroethane: EtOH (55:35:10) with 0.5% TFA. Retention time was 15.93 min for peak 1 (3f-I) and 17.08 for peak 2 (3f-II).
26. 3) for 3f-I: 1.48 (d, J = 6.3 Hz, 3H), 1.55-1.90 (m, 8H), 2.00 (s, 3H), 2.09 (br s, 1H), 3.47 (br s, 1H), 3.60 (br s, 1H), 3.92 (s, 3H), 4.29 (d, J = 15.3 Hz, 1H), 4.54 (m, 1H), 5.46 (d, J = 17.1 Hz, 1H), 5.53 (d, J = 17.1 Hz, 1H), 6.87 (d, J = 6.9 Hz, 1H), 6.98 (d, J = 7.4 Hz, 1H), 7.29 (m, 2H), 7.45 (m, 1H), 7.57 (d, J = 7.5 Hz, 1H); for 3f-II: 1.39 (d, J = 6.9 Hz, 3H), 1.55-1.70 (m, 7H), 2.00 (s, 3H), 2.15 (br s, 1H), 3.40-3.70 (br s, 3H), 3.92 (s, 3H), 4.20 (d, J = 13.8 Hz, 1H), 4.54 (dd, J = 6.3, 14.4 Hz, 1H), 5.35 (d, J = 17.1 Hz, 1H), 5.52 (d, J = 16.5 Hz, 1H), 6.84 (d, J = 7.5 Hz, 1H), 6.97 (d, J = 7.4 Hz, 1H), 7.30 (m, 2H), 7.44 (m, 1H), 7.57 (d, J = 8.1 Hz, 1H).
27. CCDC 684002 contains the supplementary crystallographic data for this paper. These data can be obtained via the CDCC website (www.ccdc.cam.ac.uk), or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK.
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