344585-18-8Relevant academic research and scientific papers
Synthesis and Properties of 1,3-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: V. 1-(Bicyclo[2.2.1]heptan-2-yl)-3-R- and 1-(1,7,7-Tricyclo[2.2.1]heptan-2-yl)-3-R-ureas
Pitushkin,Burmistrov,Saeef, M. H. Abbas,Vernigora,Butov
, p. 1893 - 1904 (2021/01/12)
Abstract: A series of 1,3-disubstituted ureas containing a bicyclic lipophilic group ofnatural origin were synthesized by the reactions of bicyclo[2.2.1]heptane-2-ylisocyanate with amines in yields of up to 82% and by the reactions ofbicyclo[2.2.1]heptan-2-amine and 1,7,7-trimethylbicyclo[2.2.1]heptan-2-aminewith 1,1'-carbonyldiimidazole in yields of up to 94%. The synthesized ureas arepotent inhibitors of RNA virus replication and soluble epoxide hydrolase.
Alkyl Isocyanates via Manganese-Catalyzed C-H Activation for the Preparation of Substituted Ureas
Huang, Xiongyi,Zhuang, Thompson,Kates, Patrick A.,Gao, Hongxin,Chen, Xinyi,Groves, John T.
supporting information, p. 15407 - 15413 (2017/11/06)
Organic isocyanates are versatile intermediates that provide access to a wide range of functionalities. In this work, we have developed the first synthetic method for preparing aliphatic isocyanates via direct C-H activation. This method proceeds efficiently at room temperature and can be applied to functionalize secondary, tertiary, and benzylic C-H bonds with good yields and functional group compatibility. Moreover, the isocyanate products can be readily converted to substituted ureas without isolation, demonstrating the synthetic potential of the method. To study the reaction mechanism, we have synthesized and characterized a rare MnIV-NCO intermediate and demonstrated its ability to transfer the isocyanate moiety to alkyl radicals. Using EPR spectroscopy, we have directly observed a MnIV intermediate under catalytic conditions. Isocyanation of celestolide with a chiral manganese salen catalyst followed by trapping with aniline afforded the urea product in 51% enantiomeric excess. This represents the only example of an asymmetric synthesis of an organic urea via C-H activation. When combined with our DFT calculations, these results clearly demonstrate that the C-NCO bond was formed through capture of a substrate radical by a MnIV-NCO intermediate.
Structure-activity relationship of N,N′-disubstituted pyrimidinetriones as CaV1.3 calcium channel-selective antagonists for Parkinson's disease
Kang, Soosung,Cooper, Garry,Dunne, Sara Fernandez,Luan, Chi-Hao,Surmeier, D. James,Silverman, Richard B.
, p. 4786 - 4797 (2013/07/19)
CaV1.3 L-type calcium channels (LTCCs) have been a potential target for Parkinson's disease since calcium ion influx through the channel was implicated in the generation of mitochondrial oxidative stress, causing cell death in the dopaminergic neurons. Selective inhibition of CaV1.3 over other LTCC isoforms, especially CaV1.2, is critical to minimize potential side effects. We recently identified pyrimidinetriones (PYTs) as a CaV1.3-selective scaffold; here we report the structure-activity relationship of PYTs with both CaV1.3 and CaV1.2 LTCCs. By variation of the substituents on the cyclopentyl and arylalkyl groups of PYT, SAR studies allowed characterization of the CaV1.3 and Ca V1.2 LTCCs binding sites. The SAR also identified four important moieties that either retain selectivity or enhance binding affinity. Our study represents a significant enhancement of the SAR of PYTs at CaV1.3 and CaV1.2 LTCCs and highlights several advances in the lead optimization and diversification of this family of compounds for drug development.
Novel Potassium-Channel Openers: Preparation and Pharmacological Evaluation of Racemic and Optically Active N-(6-Amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine Derivatives
Eda, Masahiro,Takemoto, Tadahiro,Ono, Shin-ichiro,Okada, Takehiro,Kosaka, Keigo,et al.
, p. 1983 - 1990 (2007/10/02)
The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induced contraction of rat aorta, hypotensive activity in normotensive rats, and diuretic activity in spontaneously hypertensive rats. This led to further evaluation of compound (+/-)-10 and selection of (+)-N-(6-amino-3-pyridyl)-N'-hept-2-yl>-N"-cyanoguanidine ((+)-10) (AL0670) for development as an antihypertensive agent. Although AL0670 is regarded as a pinacidil-type K+-channel opener, it showed different pharmacological and conformational profiles from pinacidil.
SYNTHESIS OF ALIPHATIC ISOCYANATES VIA A TWO-PHASE HOFMANN REACTION
Sy, Anita O.,Raksis, Joseph W.
, p. 2223 - 2226 (2007/10/02)
A convenient method of preparing aliphatic isocyanates via a two-phase Hofmann reaction using a phase transfer catalyst is described.
