31383-67-2Relevant academic research and scientific papers
Design, synthesis and biological characterization of novel inhibitors of CD38
Dong, Min,Si, Yuan-Qi,Sun, Shuang-Yong,Pu, Xiao-Ping,Yang, Zhen-Jun,Zhang, Liang-Ren,Zhang, Li-He,Leung, Fung Ping,Lam, Connie Mo Ching.,Kwong, Anna Ka Yee,Yue, Jianbo,Zhou, Yeyun,Kriksunov, Irina A.,Hao, Quan,Cheung Lee, Hon
experimental part, p. 3246 - 3257 (2011/06/10)
Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca2+ messenger molecule, cyclic ADP-ribose, from NAD+. It is well established that this novel Ca2+ signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD+ complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound1-14). A number of these compounds exhibited moderate inhibition of the NAD+ utilizing activity of CD38, with Compound4 showing the highest potency. The crystal structure of CD38/Compound4 complex and computer simulation of Compound7 docking to CD38 show a significant role of the nicotinamide moiety and the distal aromatic group of the compounds for substrate recognition by the active site of CD38. Biologically, we showed that both Compounds4 and 7 effectively relaxed the agonist-induced contraction of muscle preparations from rats and guinea pigs. This study is a rational design of inhibitors for CD38 that exhibit important physiological effects, and can serve as a model for future drug development.
Reactivity models of 1-N-vinyluracil and synthesis of a new class of potential antiviral agents by the use of 1,3-dipolar cycloaddition reactions
Colacino,De Luca,Liguori,Napoli,Siciliano,Sindona
, p. 743 - 745 (2007/10/03)
By the use of a convergent approach based on 1,3-dipolar cycloaddition reactions between N-protected formylnitrones generated in situ and 1 -N-vinyluracil, a new class of 4′-aza-analogues of 2′,3′ -dideoxynucleosides is synthesized. Competitive reaction for the endocyclic bond of uracil also brings to a new isoxazolidine derivative fused with the pyrimidine nucleus.
SYNTHESIS AND ANTIVIRAL ACTIVITY OF 1,2,3-TRIAZOLE AND 8-AZAPURINE DERIVATIVES BEARING ACYCLIC SUGARS
Yokoyama, Masataka,Nakao, Eiko,Sujino, Keiko,Watanabe, Satoshi,Togo, Hideo
, p. 1669 - 1685 (2007/10/02)
A variety of 1,2,3-triazole and 8-azapurine derivatives bearing acyclic sugar moieties were synthesized by the reaction of acyclic sugar azides with α-cyanoacetamide, norbornadiene, and acetylene derivatives, respectively.Antiviral tests of these compound
Substituted and unsubstituted 13-(alkoxy)methoxy derivatives of the avermectin aglycones, compositions and use
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, (2008/06/13)
Novel substituted and unsubstituted 13-(alkoxy)methoxy derivatives of the avermectin aglycones are useful as anthelmintic and antiparasitic agents. The compounds are also useful as pesticides and insecticides against agricultural pests. Included herein are novel intermediates useful in the process for preparing said avermectin aglycone derivatives. Compositions of said derivatives and methods of administering said compositions are also disclosed.
Studies on Nucleosides: Part XIII - Synthesis and Antiviral Activity of Acyclic Analogues of Spongosine
Singh, P. K.,Saluja, Sunita,Pratap, Ram,George, C. X.,Bhakuni, D. S.
, p. 823 - 827 (2007/10/02)
6-Amino-9--2-methoxypurine (9), 6-amino-2-ethoxy-9-purine (10) and 6-amino-9-(2-hydroxyethoxymethyl)-2-methoxypurine (17) have been synthesized.Condensation of 2,6-dichloropurine (4) with 2-O-chloromethyl-1,3-di-O-benzylglycerol (5) furnishes the protected acyclic nucleosides 8 (yield 50percent) and 7 (yield 7percent).Amination of 7 and 8 affords 6 and 13 respectively.Treatment of 13 with sodium methoxide and ethoxide gives 11 and 12 respectively.Deblocking of 11 and 12 with Pd-C/H2 finally produces 9 and 10 respectively.Condensation of 4 with 1-O-benzyl-2-O-chloromethylethanediol gives 19 (yield 55percent) and 15 (yield 5percent).Amination of 19 affords 18 which on treatment with sodium methoxide furnishes 16.Deblocking of 16 with Pd-C/H2 gives 17.Compounds 9, 10, 11, 13 and 17 in combination with interferon inducer, mycoviral ds RNA, exhibit 16, 0, 16, 40 and 40percent enhancement of protection respectively against the semliki forest virus in Swiss albino mice.
