NMR Assignments of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine

doi:10.11938/cjmr20192776

Abstract

Abstract: 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine is a national class I innovative antiepileptic drug candidate in clinical trials with independent intellectual property rights. The ¹H, ¹³C and ¹⁵N NMR spectra of the compound were acquired at 500 MHz. Aided by GIAO (Gauge-Independent Atomic Orbital)-NMR quantum chemistry calculation, the chemical shifts of the compound were assigned, providing elaborate structural information of the compound. Linear regression comparison results showed good consistency between the theoretical predictions and the experimental data for structural elucidations.

Key words: liquid-state NMR, structural assignment, 2D NMR, ¹⁵N NMR, 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine, density functional theory calculation

CLC Number:

O656.4

WANG Si-hong, ZHANG Jing-dong, YIN Xiu-mei, LI Dong-hao, KAN Yu-he, HU Wei. NMR Assignments of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine[J]. Chinese Journal of Magnetic Resonance, 2020, 37(3): 390-398.

References

[1] 国家药典委员会. 核磁共振波谱法[S]//中华人民共和国药典四部. 2020年版. 北京:中国医药科技出版社, 2020:0441.
[2] WANG Y L, WANG X J, WANG Z W. Spectral analyses and structural elucidation of azilsartan[J]. Chinese J Magn Reson, 2019, 36(3):350-358.王亚兰, 王晓静, 王志伟. 阿齐沙坦的波谱学数据及结构确证[J]. 波谱学杂志, 2019, 36(3):350-358.
[3] WEI H Q, YU J, BI C F, et al. An NMR study of N-isobutyryl-3'-O-(1-fluoro-1,1,3,3-tetraisopropyl-1,3-disiloxane-3-yl)-2'-benzyloxycarbonyl-guanosine[J]. Chinese J Magn Reson, 2019, 36(1):93-102.魏会强, 于江, 毕常芬, 等. N-异丁酰基-3'-O-(1-氟-1,1,3,3-四异丙基-1,3-二硅氧烷-3-基)-2'-苄氧羰基鸟苷的NMR研究[J]. 波谱学杂志, 2019, 36(1):93-102.
[4] WANG S H, KAN Y H. Experimental and theoretical studies of the absolute configuration of (2S,1'R) and (2R,1'R)-2-acetoxymethyl-3-phenyl-N-(1'-phenylethyl)-propionamide[J]. Journal of Molecular Structure, 2010, 981(1):159-162.
[5] WANG S H, YIN X M, KAN Y H, et al. Assignment of carbon and proton chemical shifts of 3-nitrobenzanthron[J]. Journal of Yanbian Uviversity (Natural Science), 2012, 38(2):138-141.王思宏, 尹秀梅, 阚玉和, 等. 3-硝基苯并蒽酮的碳和氢的化学位移归属[J]. 延边大学学报(自然科学版), 2012, 38(2):138-141.
[6] LI X, ZHANG H J, WANG Q, et al. Current study of the mechanism of action of the potential anti-epileptic agent Q808[J]. Molecules, 2017, 22(7):1134.
[7] SUN X Y, WEI C X, DENG X Q, et al. Evaluation of the anticonvulsant activity of 6-(4-chlorophenyoxy)-tetrazolo[5,1-a]phthalazine in various experimental seizure models in mice[J]. Pharmacol Rep, 2010, 62(2):273-277.
[8] YU H L, ZHANG F, LAN T, et al. Effects of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine on anticoagulation in mice and the inhibition of experimental thrombosis in rats[J]. J Cardiovasc Pharmacol, 2014, 64(6):560-566.
[9] YU H L, ZHANG F, LI Y J, et al. Anti-inflammatory and antinociceptive effects of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine in mice[J]. Pharmacol Rep, 2012, 64(5):1155-1165.
[10] ZHANG F, JIANG H C, CHEN X R, et al. Antidepressant-like effect of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine in mice[J]. Chin J Pharm Toxicol, 2013, 27(5):783-788.
[11] SUN X Y, WEI C X, DENG X Q, et al. Synthesis and primary anticonvulsant activity evaluation of 6-alkyoxyl-tetrazolo[5,1-a]phthalazine derivatives[J]. Arzneim Forsch, 2010, 60(6):289-292.
[12] LI L, LIU C, QUAN Z S, et al. Structure identification and determination of therelated substances in the first type of new anti-epileptic drug Q808[J]. Journal of Yanbian Uviversity (Natural Science), 2016, 39(2):103-107.李龙, 刘冲, 全哲山, 等. 抗癫痫一类新药Q808有关物质的结构确定及含量测定[J]. 延边大学医学学报, 2016, 39(2):103-107.
[13] WOLINSKI K, HINTON J F, PULAY P. Efficient implementation of the gauge-independent atomic orbital method for NMR chemical shift calculations[J]. J Am Chem Soc, 1990, 112(23):8251-8260.
[14] JENSEN F. Segmented contracted basis sets optimized for nuclear magnetic shielding[J]. J Chem Theory Comput, 2015, 11(1):132-138.
[15] GAUSS J. Calculation of NMR chemical shifts at second-order many-body perturbation theory using gauge-including atomic orbitals[J]. Chem Phys Lett, 1992, 191(6):614-620.
[16] LODEWYK M W, SIEBERT M R, TANTILLO D J. Computational prediction of ¹H and ¹³C chemical shifts:a useful tool for natural product, mechanistic, and synthetic organic chemistry[J]. Chem Rev, 2012, 112(3):1839-1862.
[17] GAO P, WANG X, YU H. Towards an accurate prediction of nitrogen chemical shifts by density functional theory and gauge-including atomic orbital[J]. Adv Theor Simul, 2019, 2(2):1800148.
[18] 于德泉, 杨峻山. 分析化学手册:核磁共振波谱分析[M]. 北京:化学工业出版社, 1999.
[19] 孔令义. 复杂天然产物波谱解析[M]. 北京:中国医药科技出版社, 2012.
[20] CMOCH P, STEFANIAK L, MELZER E, et al. ¹H, ¹³C and ¹⁵N NMR study of some triazolo-and tetrazolopyridazines and thioxotriazolopyridines[J]. Magn Reson Chem, 1999, 37(7):493-497.
[21] STEFANIAK L, ROBERTS J D, WITANOWSKI M, et al. A nitrogen-15 NMR investigation of some azolopyridines[J]. Org Magn Reson, 1984, 22(4):209-214.
[22] XU X, ZHU C L, KAN Y H. Sensing mechanism and molecular design of FRET based dual-emission fluorescent probe[J]. Journal of Huaiyin Teachers College (Natural Science Edition), 2019, 18(1):41-47.徐鑫, 朱长磊, 阚玉和. 基于FRET的双发射荧光探针的传感机理及分子设计[J]. 淮阴师范学院学报(自然科学版), 2019, 18(1):41-47.