CAS: 169939-94-0; (7S)-7-((Dimethylamino)Methyl)-22,25-Dihydro-11H,21H,31H-6-Oxa-1,3(3,1)-Diindola-2(3,4)-Pyrrolacyclononaphane-22,25-Dione

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(9S)-6,7,10,11-Tetrahydro-9-{[(Methylsulfonyl)Oxy]Methyl}-9H,18H-5,21:12,17-Dimethenodibenzo[e,K]Pyrrolo[3,4-H][1,4,13]-Oxadiazacyclohexadecine-18,20(19H)-Dione 169940-46-9

📜Tert-Butyl-[(2S)-4-Iodo-2-(2-Iodoethoxy)Butoxy]-Diphenylsilane置于吡啶,氢氧化钾,Caesium Carbonate,六甲基二硅氮烷体系中,用 四氢呋喃,二氯甲烷,水 用作溶剂,化学反应 40.0H,反应生成鲁伯斯塔
参考文献:(S)-13-[(Dimethylamino)Methyl]-10,11,14,15-Tetrahydro-4,9:16,21-Dimetheno-1H,13H-Dibenzo[e,K]Pyrrolo[3,4-H][1,4,13]Oxadiazacyclohexadecene-1,3(2H)-Dione (Ly333531) And Related Analogues: Isozyme Selective Inhibitors Of Protein Kinase Cβ
标题:(S)-13-[(Dimethylamino)Methyl]-10,11,14,15-Tetrahydro-4,9:16,21-Dimetheno-1H,13H-Dibenzo[e,K]Pyrrolo[3,4-H][1,4,13]Oxadiazacyclohexadecene-1,3(2H)-Dione (Ly333531) And Related Analogues: Isozyme Selective Inhibitors Of Protein Kinase Cβ
摘要:Protein Kinase C (Pkc) Is A Family Of Closely Related Serine And Threonine Kinases. Overactivation Of Some Pkc Isozymes Has Been Postulated To occur In Several Disease States,Including Diabetic Complications. Selective Inhibition Of Overactivated Pkc Isozymes May Offer A Unique Therapeutic Approach To Disease States Such As Diabetic Retinopathy. A Novel Series Of 14-Membered Macrocycles Containing A N-N'-Bridged Bisindolylmaleimide Moiety Is Described. A Panel Of Eight Cloned Human Pkc Isozymes (Alpha,Beta I,Beta Ii,Gamma,Delta,Epsilon,Zeta,Eta) Was Used To Identify The Series And Optimize The Structure And Associated Activity Relationship. The Dimethylamine Analogue Ly333531 (1),(S)-13-[(Dimethylamino)Methyl]-10,11,14,15-Tetrahydro-4,9:16,21-Dimetheno-1H,13H-Dibenzo[e,K]Pyrrolo[3,4-H][1,4,13]Oxadiazacyclohexadecene-1,3(2H)-Dione,Inhibits The Pkc Beta I (Ic50 = 4.7 Nm) And Pkc Beta Ii (Ic50 = 5.9 Nm) Isozymes And Was 76-And 61-Fold Selective For Inhibition Of Pkc Beta I And Pkc Beta Ii In Comparison To Pkc Alpha,Respectively. The Additional Analogues Described In The Series Are Also Selective Inhibitors Of Pkc Beta. Ly333531 (1) Exhibits Atp Dependent Competitive Inhibition. Of Pkc Beta I And Is Selective For Pkc In Comparison To Other Atp Dependent Kinases (Protein Kinase A,Calcium Calmodulin,Caesin Kinase,Src Tyrosine Kinase). The Cellular Activity Of The Series Was Assessed Using Bovine Retinal Capillary Endothelial Cells. Retinal Endothelial Cell Dysfunction Has Been Implicated In The Development Of Diabetic Retinopathy. Plasminogen Activator Activity Stimulated By A Phorbol Ester (4 Beta-Phorbol 12,13-Dibutyrate) In Endothelial Cells Was Inhibited By The Compounds In The Series With Ed(50) Values Ranging From 7.5 To 0.21 Mu M. A Comparison Of The Pkc Isozyme And Related Atp Dependent Kinase Inhibition Profiles Is Provided For The Series And Compared To The Profile For Staurosporine,A Nonselective Pkc Inhibitor. The Cellular Activity Of The Series Is Compared With That Of The Kinase Inhibitor Staurosporine.
Doi:10.1021/jm950588Y

专利信息

专利号:US-10005720-B2
优先权日:2013-04-05
标题:Compounds useful for the treatment of metabolic disorders and synthesis of the same
发明人：SEXTON JONATHAN Z; BRENMAN JAY E; MUSSO DAVID L
权利人:NORTH CAROLINA CENTRAL UNIV; UNIV NORTH CAROLINA CHAPEL HILL
摘要:The present invention provides compounds of Formula (I): wherein variables X, Y, Z and R1 are as described herein. Some of the compounds described herein are glutamate dehydrogenase activators. The invention is also directed to pharmaceutical compositions comprising these compounds, uses of these compounds and compositions in the treatment of metabolic disorders as well as synthesis of the compounds.

专利号:US-8703812-B2
优先权日:2005-07-29
标 题 :Protein synthesis required for long-term memory is induced by PKC activation on days preceding associative learning
发明人：ALKON DANIEL L
权利人:ALKON DANIEL L; BRNI NEUROSCIENCES INST
摘要:The present invention provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to stimulate the synthesis of proteins sufficient to consolidate long-term memory. The present invention also provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to downregulate PKC.

专利号:US-2013331427-A1
优先权日:2006-07-28
标题:Methods of stimulating cellular growth, synaptic, remodeling and consolidation of long-term memory
发明人：ALKON DANIEL L
权利人:BRNI NEUROSCIENCES INST; BRNI NEUROSCIENCES INST
摘要:The present invention provides methods of slowing or reversing the loss of memory and learning comprising the steps of contacting an effective amount of a PKC activator with a protein kinase C (PKC) in a subject identified with memory loss slowing or reversing memory loss. The present invention provides methods of stimulating cellular growth, neuronal growth, dendritic growth, dendritic spine formation, dendritic spine density, and the translocation of ELAV to proximal dendrites, and synaptic remodeling. The present invention also provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to stimulate the synthesis of proteins sufficient to consolidate long-term memory. The present invention also provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to downregulate PKC.

专利号:US-2018370905-A1
优先权日:2013-04-05
标题:Compounds Useful for the Treatment of Metabolic Disorders and Synthesis of the Same

专利号:US-2016046560-A1
优先权日:2013-04-05
标题 :Compounds useful for the treatment of metabolic disorders and synthesis of the same

专利号:US-11319320-B2
优先权日:2017-11-06
标题:PIM kinase inhibitor compositions, methods, and uses thereof
发明人：BURK MARK J; CHEN BRANDON; LI JINGYI; BACHAN SHAWN
权利人:SNAP BIO INC
摘要:This application relates to compounds of formulae (I) and (II) and compositions thereof useful as inhibitors of PIM kinases. Also provided are methods of synthesis and methods of use of PIM inhibitors in treating individuals suffering from cancerous malignancies.