- Synthesis of linear and angular aryl-morpholino-naphth-oxazines, their DNA-PK, PI3K, PDE3A and antiplatelet activity
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To continue our study of 2-morpholino-benzoxazine based compounds, which show useful activity against PI3K family enzymes or antiplatelet activity, we designed and synthesized a series of linear 6.7-fused, 5,6-angular fused and 7,8-angular fused-aryl-morpholino-naphth-oxazines. The compounds were prepared from substituted 2-hydroxynaphthoic acid to give the corresponding thioxo analogues 8, 9, 15 and 19. The thioxo products were then converted to the morpholino substituted analogue. The aryl group was introduced by Suzuki coupling of bromo precursors. The products were evaluated for activity at PI3K family enzymes and as platelet aggregation inhibitors and compared to reported unsubstituted analogues. The linear 6.7-fused product 13a and 13b were moderated potent but selective PI3Kδ isoform inhibitors (IC50?=?7.7 and 5.61?μM). Good antiplatelet activity was noticed for the angular 7,8-fused compounds 22a, b, k and l with IC50?=?3.0,14.0, 2.0 and 5.0?μM respectively. The antiplatelet activity is independent of PDE3.
- Morrison, Rick,Zheng, Zhaohua,Jennings, Ian G.,Thompson, Philip E.,Al-Rawi, Jasim M.A.
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- Construction of Axially Chiral Arylborons via Atroposelective Miyaura Borylation
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Compared with the well-developed centrally chiral boron chemistry, C-B axially chiral chemistry remains elusive and challenging. Herein we report the first atroposelective Miyaura borylation of bromoarenes with unsymmetrical diboron reagents for the direct catalytic synthesis of optically active atropisomeric arylborons. This reaction features broad substrate scope and produces axially chiral arylborons with high yields and good enantioselectivities.
- He, Yong,Li, Wangyang,Mao, Yanfei,Song, Qiuling,Wang, Hao,Xu, Jie,Yang, Kai
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supporting information
p. 10048 - 10053
(2021/07/21)
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- Nickel-Catalyzed Directed Cross-Electrophile Coupling of Phenolic Esters with Alkyl Bromides
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Herein, we demonstrate the successful use of robust phenolic esters as an electrophilic acyl source in the reaction with diverse primary and secondary unactivated alkyl bromides. The cleavage of the relatively inert C-O bond is facilitated by the neighboring coordinating hydroxyl or sulfonamide moiety. By circumventing the use of pregenerated organometallics, this method allows efficient preparation of a variety of o-hydroxyl and tosyl-protected o-amino aryl ketones with high compatibility with a wide range of functionalities.
- Ding, Decai,Wang, chuan,Yang, feiyan
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supporting information
p. 9203 - 9209
(2020/12/22)
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- PHARMACEUTICAL PREPARATIONS COMPRISING INSULIN, ZINC IONS AND A ZINC-BINDING LIGAND
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Novel preparations comprising branched ligands for the HisB10 Zn2+ sites of the R-state insulin hexamer. The preparations have a prolonged action designed for flexible injection regimes.
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Page/Page column 247
(2008/06/13)
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- PHAMACEUTICAL PREPARATIONS COMPRISING INSULIN
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Novel preparations comprising ligands for the HisB10 Zn2+ sites of the R-state insulin hexamer wherein the ligand is extended by protamine that are capable of prolonging the ac-tion of insulin preparations.
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Page/Page column 242
(2010/02/15)
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- Stabilised insulin compositions
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The present invention provides pharmaceutical compositions comprising insulin and novel ligands for the HisB10 Zn2+ sites of the R-state insulin hexamer. The resulting preparations have improved physical and chemical stability.
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Page/Page column 131
(2008/06/13)
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- Novel ligands for the hisb10 zn2+ sites of the r-state insulin hexamer
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Novel ligands for the HisB10 Zn2+ sites of the R-state insulin hexamer that are capable of prolonging the action of insulin preparations are disclosed.
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- Modifier composition for azo pigments based on 2-hydroxy-3-naphthoic acid
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The use of alpha-substituted-2-hydroxy-3-naphthoic acids to replace part of the conventional 2-hydroxy-3-naphthoic acid coupling component results in improved azo dyes.
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