Citation: MIAO Jun-Qiu, HE Su-Hai, DONG Xiu-Shan, LIANG Tai-Gang, LI Qing-Shan. 3D-QSAR Studies on 3-Substituted N-Benzhydryl-nortropane Analogs as Nociception Receptor Agonists[J]. Chinese Journal of Structural Chemistry, ;2016, 35(9): 1319-1327. doi: 10.14102/j.cnki.0254-5861.2011-1104 shu

3D-QSAR Studies on 3-Substituted N-Benzhydryl-nortropane Analogs as Nociception Receptor Agonists

1.
a College of Pharmacy, Shanxi Medical University, Taiyuan 030001, China;
2.
b Department of General Surgery, Shanxi Dayi Hospital, Taiyuan 030032, China

Received Date: 29 December 2015
Available Online: 25 May 2016
Fund Project: This work was supported by the National Natural Science Foundation of China (No. 81101687) (No. 81101687)

The nociceptin receptor(NOP) has been involved in multiple biological functions, including pain, anxiety, cough, substance abuse, cardiovascular control, and immunity. Thus, selective NOP agonists might have clinical potential for the treatment of related diseases. In the present work, three-dimensional quantitative structure-activity relationship(3D-QSAR) studies were performed on a series of 3-substituted N-benzhydryl-nortropane analogs as NOP agonists using comparative molecular field analysis(Co MFA) and comparative molecular similarity indices analysis(CoM SIA) techniques. The statistically significant models were obtained with 54 compounds in training set by ligand-based atom-by-atom matching alignment. The CoM FA model gave cross-validated coefficient(q²) value of 0.530 using 6 components, non-cross-validated(r²) value of 0.921 with estimated F value of 93.668, and standard error of estimate(SEE) of 0.185. The best Co MSIA model resulted in q²=0.592, r²=0.945, N=10, SEE=0.162, and F=75.654, based on steric, electrostatic, hydrophobic and hydrogen bond acceptor fields. The predictive ability of the Co MFA and CoM SIA models was further validated using a test set of 18 molecules that were not included in the training set, which resulted in predictive correlation coefficients(r_pred²) of 0.551 and 0.637, respectively. Moreover, the CoM FA and CoM SIA contour maps identified the features important for exhibiting potent binding affinities on NOP, and can thus serve as a useful guide for the design of potential NOP agonists.
- QSAR,
- CoMFA,
- CoMSIA,
- 3-substituted N-benzhydryl-nortropane analogs,
- nociception receptor agonists
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  Ke Wu , Xiuqin Ruan , Shuolei Jia , Enyuan Wang , Qingfa Zhou . DABCO-catalyzed [3+4] annulations of Schiff bases with α-substituted allenes: Construction of functionalized benzazepine derivatives. Chinese Chemical Letters, 2025, 36(7): 110646-. doi: 10.1016/j.cclet.2024.110646
7. [7]
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8. [8]
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16. [16]
  Liang Ma , Zhou Li , Zhiqiang Jiang , Xiaofeng Wu , Shixin Chang , Sónia A. C. Carabineiro , Kangle Lv . Effect of precursors on the structure and photocatalytic performance of g-C3N4 for NO oxidation and CO2 reduction. Chinese Journal of Structural Chemistry, 2024, 43(11): 100416-100416. doi: 10.1016/j.cjsc.2024.100416
17. [17]
  Yanghanbin Zhang , Dongxiao Wen , Wei Sun , Jiahe Peng , Dezhong Yu , Xin Li , Yang Qu , Jizhou Jiang . State-of-the-art evolution of g-C3N4-based photocatalytic applications: A critical review. Chinese Journal of Structural Chemistry, 2024, 43(12): 100469-100469. doi: 10.1016/j.cjsc.2024.100469
18. [18]
  Haitao Wang , Lianglang Yu , Jizhou Jiang , Arramel , Jing Zou . S-Doping of the N-Sites of g-C₃N₄ to Enhance Photocatalytic H₂ Evolution Activity. Acta Physico-Chimica Sinica, 2024, 40(5): 2305047-0. doi: 10.3866/PKU.WHXB202305047
19. [19]
  Xuejiao Wang , Suiying Dong , Kezhen Qi , Vadim Popkov , Xianglin Xiang . Photocatalytic CO₂ Reduction by Modified g-C₃N₄. Acta Physico-Chimica Sinica, 2024, 40(12): 2408005-0. doi: 10.3866/PKU.WHXB202408005
20. [20]
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