1 Scientific RepoRts | 7: 12535 | DOI:10.1038/s41598-017-12082-3 www.nature.com/scientificreports pharmacological use of a novel scafold, anomeric N,N-diarylamino tetrahydropyran: molecular similarity search, chemocentric target profling, and experimental evidence Arramshetti Venkanna 1 , Oh Wook Kwon 2 , Sualiha Afzal 1 , Cheongyun Jang 1 , Kyo Hee Cho 1 , Dharmendra K. Yadav 1 , Kang Kim 1 , Hyeung-geun park 3 , Kwang-Hoon Chun 1 , Sun Yeou Kim 1 & Mi-hyun Kim 1 Rational drug design against a determined target (disease, pathway, or protein) is the main strategy in drug discovery. However, regardless of the main strategy, chemists really wonder how to maximize the utility of their new compounds by drug repositioning them as clinical drug candidates in drug discovery. In this study, we started our drug discovery “from curiosity in the chemical structure of a drug scafold itself” rather than “for a specifc target”. As a new drug scafold, anomeric diarylamino cyclic aminal scafold 1, was designed by combining two known drug scafolds (diphenylamine and the most popular cyclic ether, tetrahydropyran/tetrahydrofuran) and synthesized through conventional Brønsted acid catalysis and metal-free α-C(sp 3 )–H functionalized oxidative cyclization. To identify the utility of the new scafold 1, it was investigated through 2D and 3D similarity screening and chemocentric target prediction. The predicted proteins were investigated by an experimental assay. The scafold 1 was reported to have an antineuroinfammatory agent to reduce NO production, and compound 10 concentration-dependently regulated the expression level of IL-6, PGE-2, TNF-α, ER-β, VDR, CTSD, and iNOS, thus exhibiting neuroprotective activity. In drug discovery, one of the important roles of a synthetic chemist is the rational design of novel drug scafolds with a high selectivity and promising activity, and another important role is to synthesize them. Although drug discovery starts with a target disease (phenotype-based drug discovery) or a target molecule (target-based drug discovery), chemists are interested in the possible uses of their synthesized molecules. Since the 21 st century, synthetic organic chemists or medicinal chemists have strongly studied useful approaches for which compounds should be synthesized and how to synthesize them 1–4 . Using these approaches, although the therapeutic potential of privileged scafolds has been well investigated, it is still rare to select unprecedented scafolds (with structural novelty) as a starting point of in silico target fshing due to insufcient clues or evidence on plausible targets 5–7 . Terefore, currently, it is neither easy nor efcient for chemists to start drug discovery “from curiosity in chemical structure”. Despite the inefciency, drug discovery driven by the novelty of a drug scafold can compensate the general approach driven by a specifc target to broaden the drug space of artifcial drugs 8 . Moreover, it is not recommended to synthesize the unprecedented scafold without the data on the application of scafold. But if an organic chemist expands an efcient reaction method for synthesizing an unprecedented 1 Gachon institute of Pharmaceutical Science & Department of Pharmacy, college of Pharmacy, Gachon University, 191 Hambakmoeiro, Yeonsu-gu, Incheon, Republic of Korea. 2 Natural F&P Corp. 152 Saemal-ro, Songpa-gu, Seoul, Korea. 3 Research Institute of Pharmaceutical Science and College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Correspondence and requests for materials should be addressed to S.K. (email: sunnykim@ gachon.ac.kr) or M.-h.K. (email: kmh0515@gachon.ac.kr) Received: 29 March 2017 Accepted: 29 August 2017 Published: xx xx xxxx OPEN