- COMPOUNDS AND METHODS FOR TREATING ADDICTION AND RELATED DISORDERS
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The present invention relates to compounds and methods of use thereof for treatment of certain disorders and conditions, for example an addiction or compulsive disorder.
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- Compounds and methods for treating neurological and cardiovascular conditions
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The present invention relates to compounds and methods of use thereof for treatment of certain disorders and conditions, for example brain injuries such as stroke or traumatic brain injuries.
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- South (S)- and north (N)-methanocarba-7-deazaadenosine analogues as inhibitors of human adenosine kinase
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Adenosine kinase (AdK) inhibitors raise endogenous adenosine levels, particularly in disease states, and have potential for treatment of seizures, neurodegeneration, and inflammation. On the basis of the South (S) ribose conformation and molecular dynamics (MD) analysis of nucleoside inhibitors bound in AdK X-ray crystallographic structures, (S)- and North (N)-methanocarba (bicyclo[3.1.0]hexane) derivatives of known inhibitors were prepared and compared as human (h) AdK inhibitors. 5′-Hydroxy (34, MRS4202 (S); 55, MRS4380 (N)) and 5′-deoxy 38a (MRS4203 (S)) analogues, containing 7- and N6-NH phenyl groups in 7-deazaadenine, robustly inhibited AdK activity (IC50 ~ 100 nM), while the 5′-hydroxy derivative 30 lacking the phenyl substituents was weak. Docking in the hAdK X-ray structure and MD simulation suggested a mode of binding similar to 5′-deoxy-5-iodotubercidin and other known inhibitors. Thus, a structure-based design approach for further potency enhancement is possible. The potent AdK inhibitors in this study are ready to be further tested in animal models of epilepsy.
- Toti, Kiran S.,Osborne, Danielle,Ciancetta, Antonella,Boison, Detlev,Jacobson, Kenneth A.
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supporting information
p. 6860 - 6877
(2016/08/05)
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- Stereoselective synthesis and anti-HCV activity of conformationally restricted 2′-C-substituted carbanucleosides
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Conformationally restricted 2′-C-azido-, hydroxy- and fluoromethyl-carbanucleosides 4b-f were efficiently synthesized via the stereoselective conversion of ketone 7 to epoxide 14, followed by the stereoselective opening of the epoxide with nucleophiles (O
- Choi, Won Jun,Ko, Yun Jung,Chandra, Girish,Lee, Hyuk Woo,Kim, Hea Ok,Koh, Hyo Jung,Moon, Hyung Ryong,Jung, Young Hoon,Jeong, Lak Shin
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p. 1253 - 1261
(2012/03/07)
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- A direct, efficient method for the preparation of siRNAs containing ribo-like north bicyclo[3.1.0]hexane pseudosugars
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An efficient method for the preparation of siRNAs modified with ribo-like North bicyclo[3.1.0]hexane pseudosugars is described. The combined use of 2-O-(2-cyanoethoxymethyl) (CEM) and 2-O-TBDMS protection was successfully employed for RNA synthesis with the added advantage that both groups were efficiently removed in a single step. The resulting North ribo-methanocarba- modified siRNAs are compatible with the intracellular RNAi machinery and can mediate specific degradation of target mRNA.
- Terrazas, Montserrat,Avino, Anna,Siddiqui, Maqbool A.,Marquez, Victor E.,Eritja, Ramon
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p. 2888 - 2891
(2011/08/02)
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- Total syntheses of a conformationally locked North-type methanocarba puromycin analogue and a dinucleotide derivative
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An original synthetic approach for the first synthesis of an enantiopure methanocarba puromycin (3'-α-aminoacylamino-3'-deoxyadenosine) analogue and its cytidine dinucleotide derivative is described. Each compound is conformationally locked in a North-typ
- Michel, Benoit Y.,Strazewski, Peter
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experimental part
p. 6244 - 6257
(2010/03/26)
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- Asymmetric synthesis of cyclopropyl-fused 2′-C-methylcarbanucleosides as potential anti-HCV agents
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Novel 2′-C-methyl-cyclopropyl-fused carbocyclic nucleosides as potential anti-HCV agents were stereoselectively synthesized, utilizing regioselective cleavage of the isopropylidene group and cyclic sulfate chemistry as key steps. Copyright Taylor & Franci
- Jeong, Lak Shin,Lee, Jeong A.,Kim, Hea Ok,Tosh, Dilip K.,Moon, Hyung Ryong,Lee, Seung-Jin,Lee, Kang Man,Sheen, Yhun Y.,Chun, Moon Woo
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p. 1021 - 1024
(2008/09/16)
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- Stereoselective synthesis of 2′-C-methyl-cyclopropyl-fused carbanucleosides as potential anti-HCV agents
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(Chemical Equation Presented) Stereoselective synthesis of 2′-C-methyl-cyclopropyl-fused carbanucleosides was accomplished via stereoselective cyclopropanation, regioselective cleavage of the isopropylidene group, stereoselective Grignard reaction, and cy
- Lee, Jeong A.,Hea, Ok Kim,Tosh, Dilip K.,Hyung, Ryong Moon,Kim, Sanghee,Lak, Shin Jeong
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p. 5081 - 5083
(2007/10/03)
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