503551-94-8Relevant academic research and scientific papers
Attachment of a 5-nitrofuroyl moiety to spirocyclic piperidines produces non-toxic nitrofurans that are efficacious in vitro against multidrug-resistant Mycobacterium tuberculosis
Krasavin, Mikhail,Lukin, Alexei,Vedekhina, Tatiana,Manicheva, Olga,Dogonadze, Marine,Vinogradova, Tatiana,Zabolotnykh, Natalia,Rogacheva, Elizaveta,Kraeva, Liudmila,Sharoyko, Vladimir,Tennikova, Tatiana B.,Dar'in, Dmitry,Sokolovich, Evgeny
, p. 125 - 135 (2019/01/30)
A selectively antimycobacterial compound belonging to the nitrofuran class of antimicrobials has been developed via conjugation of the nitrofuran moiety to a series of spirocyclic piperidines through an amide linkage. It proved to have comparable activity against drug-sensitive (H37Rv) strain as well as multidrug-resistant, patient-derived strains of Mycobacterium tuberculosis. The compound is druglike, showed no appreciable cytotoxicity toward human retinal pigment epithelial cell line ARPE-19 in concentrations up to 100 μM and displayed low toxicity when evaluated in mice.
Discovery of polar spirocyclic orally bioavailable urea inhibitors of soluble epoxide hydrolase
Lukin, Alexey,Kramer, Jan,Hartmann, Markus,Weizel, Lilia,Hernandez-Olmos, Victor,Falahati, Konstantin,Burghardt, Irene,Kalinchenkova, Natalia,Bagnyukova, Darya,Zhurilo, Nikolay,Rautio, Jarkko,Forsberg, Markus,Ihalainen, Jouni,Auriola, Seppo,Lepp?nen, Jukka,Konstantinov, Igor,Pogoryelov, Denys,Proschak, Ewgenij,Dar'in, Dmitry,Krasavin, Mikhail
, p. 655 - 667 (2018/07/31)
Spirocyclic 1-oxa-9-azaspiro[5.5]undecan-4-amine scaffold was explored as a basis for the design of potential inhibitors of soluble epoxide hydrolase (sEH). Synthesis and testing of the initial SAR-probing library followed by biochemical testing against sEH allowed nominating a racemic lead compound (±)-22. The latter showed remarkable (> 0.5 mM) solubility in aqueous phosphate buffer solution, unusually low (for sEH inhibitors) lipophilicity as confirmed by experimentally determined logD7.4 of 0.99, and an excellent oral bioavailability in mice (as well as other pharmacokinetic characteristics). Individual enantiomer profiling revealed that the inhibitory potency primarily resided with the dextrorotatory eutomer (+)-22 (IC50 4.99 ± 0.18 nM). For the latter, a crystal structure of its complex with a C-terminal domain of sEH was obtained and resolved. These data fully validate (+)-22 as a new non-racemic advanced lead compound for further development as a potential therapeutic agent for use in such areas as cardiovascular disease, inflammation and pain.
Spirocyclic amino alcohol building blocks prepared via a Prins-type cyclization in aqueous sulfuric acid
Lukin, Alexey,Bagnyukova, Darya,Kalinchenkova, Natalya,Zhurilo, Nikolay,Krasavin, Mikhail
supporting information, p. 3311 - 3314 (2016/07/11)
A convenient Prins cyclization of various azacycloalkanones with homoallylic alcohol was achieved in aqueous sulfuric acid. The formal four-center, three-component reaction provides a facile and flexible entry into a range of spirocyclic amino alcohols wh
Multicomponent reactions: Synthesis of spirocyclic tetrahydropyran derivatives by prins cyclization
Ghosh, Arun K.,Shin, Dongwoo,Schiltz, Gary
, p. 659 - 666 (2007/10/03)
Substituted spirocyclic tetrahydropyranyl mesylates and tosylates have been synthesized in good yields using a Prins-type cyclization of various cyclic ketones, a homoallylic alcohol and either methanesulfonic or p-toluenesulfonic acid under non-aqueous conditions. The mesylates thus produced could then be transformed into the corresponding Boc-protected amines using an efficient two step procedure.
