- Time-dependent enantiodivergent synthesis via sequential kinetic resolution
-
The preparation of both enantiomers of chiral molecules is among the most fundamental tasks in organic synthesis, medicinal chemistry and materials science. Achieving this goal typically requires reversing the absolute configuration of the chiral component employed in the reaction system that is being used. The task becomes challenging when the natural source of the chiral component is not available in both configurations. Herein, we report a time-dependent enantiodivergent synthesis, in which an Ir-catalysed allylic substitution reaction uses one catalyst sequentially to promote two kinetic resolution reactions, enabling the synthesis of both enantiomers of the product using the same enantiomer of a chiral catalyst. The appropriate permutation of individual reaction rates is essential for the isolation of the chiral products in opposite configurations with high enantiopurity when quenched at different reaction times. This work provides an alternative solution for the preparation of both enantiomers of chiral molecules. [Figure not available: see fulltext.].
- Tu, Hang-Fei,Yang, Pusu,Lin, Zi-Hua,Zheng, Chao,You, Shu-Li
-
p. 838 - 844
(2020/07/03)
-
- Copper-catalyzed hydrolysis of bromoisoquinolines: Preparation of hydroxyisoquinolines
-
A complex phenomenon was observed in the process of preparing hydroxyisoquinoline through copper-catalyzed hydrolysis of bromoisoquinoline. The copper (II) complexes of hydroxyisoquinoline (L2Cu.5H2O) were characterized by high resolution mass spectra, thermogravimetric analysis, IR, 1H nuclear magnetic resonance (NMR), and 2D-NMR. The Cu (II) complexes were mononuclear and coordinated with oxygen and nitrogen atom of two hydroxyisoquinoline and five water molecules in which a strong hydrogen bond was present. Two optimized methods had been studied to prevent the formation of copper (II) complexes. The isoquinoline with 4, 5, 6, 7, and 8 hydroxyl substitutions were successfully prepared by copper-catalyzed hydrolysis of corresponding bromoisoquinoline and then workup by sodium sulfide or adjusted pH by dry ice or carbon dioxide gas.
- Xingjun, Jiang,Jianbo, He,Hongli, Chen,Weiqing, Yang,Yuanyuan, Zhang,Menglin, Ma
-
-
- Wnt signal pathway inhibitor and use thereof
-
The invention relates to heterocyclic compounds with Wnt signal channel inhibition activity, particularly including compounds, pharmaceutically acceptable salts, various isotopes, various isomers or various crystal structures thereof having a structure represented by a general formula I (shown in the specification). By the compounds and a composition of the compounds, a Wnt signal channel can be effectively inhibited and diseases related to the Wnt signal channel can be treated or prevented.
- -
-
Paragraph 0047; 0169-0172
(2017/08/10)
-
- Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors
-
Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre. Lead 14A was equipotent against both ROCK-I and ROCK-II, showed good in vivo efficacy in the spontaneous hypertensive rat model, and was further optimised to demonstrate the scope for improving selectivity over PKA versus hydroxy Fasudil 3.
- Ray, Peter,Wright, Jane,Adam, Julia,Boucharens, Sylviane,Black, Darcey,Brown, Angus R.,Epemolu, Ola,Fletcher, Dan,Huggett, Margaret,Jones, Phil,Laats, Steven,Lyons, Amanda,Man, Jos De,Morphy, Richard,Sherborne, Brad,Sherry, Lorcan,Straten, Nicole Van,Westwood, Paul,York, Mark
-
scheme or table
p. 1084 - 1088
(2011/04/16)
-
- ISOQUINOLINE DERIVATIVES AS INHIBITORS OF RHO-KINASE
-
The invention relates to 6-piperidinyl-substituted isoquinoline derivatives of the formula (I); useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.
- -
-
Page/Page column 35
(2008/06/13)
-
- PROPANAMINE DERIVATIVES AS SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS
-
There is provided a heretoaryloxy/thio 3-substituted propanamine compound of formula (I) wherein A is selected from -O- and -S-; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C1-C4 alkyl and C1-C4 alkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C1-C4 alkyl, and C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, -CF3, -CN and -CONH2; Y is selected from dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, and thienopyridyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, nitro, acetyl, -CF3, -SCF3 and cyano; Z is selected from H, OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; and pharmaceutically acceptable salts thereof.
- -
-
-
- 3-ARYLOXY/ THIO-2, 3-SUBSTITUTED PROPANAMINES AND THEIR USE IN INHIBITING SEROTONIN AND NOREPINEPHRINE REUPTAKE
-
There is provided a compound of formula (I) wherein A is selected from -O- and -S-; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C1-C4 alkyl and C1-C4 alkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C1-C4 alkyl, and C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, -CF3, -CN and -CONH2; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, nitro, acetyl, -CF3, -SCF3 and cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C1-C4 alkyl; Z is selected from OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; and pharmaceutically acceptable salts thereofwith the proviso that when Y is optionally substituted phenyl or optionally substituted 1,3-benzodioxolyl and Z is OR3 and X is optionally substituted phenyl then A is -S-.
- -
-
-
- Cleavage of aromatic methyl ethers by chloroaluminate ionic liquid reagents
-
We have discovered serendipitously that chloroaluminate ionic liquids can cleave aromatic methyl ethers under surprisingly mild conditions. Three ionic liquids, viz. [TMAH]-[Al2Cl7], [BMIM][Al2Cl7], and [EMIM][Al2Cl6I], and aluminum chloride were compared in the selective demethylation of 4,5-dimethoxyindanone at the 4-methoxy-function. The ionic liquids exhibited a remarkably high selectivity (96:4) in comparison with aluminum chloride (70:30). In addition, the reaction time was drastically shortened when the ionic liquids were used. Interestingly, the three ionic liquids displayed the same reactivity in the demethylation of 4,5-dimethoxyindanone. Considering the lower cost and the bulk availability of the precursors of [TMAH][Al2Cl7], we conclude that this is the most attractive ionic liquid from an industrial point of view. To make the large-scale application of [TMAH][Al2Cl7] feasible, we have developed a safe upscalable method for its preparation. Furthermore, the scope of ether cleavage by the ionic liquid reagent [TMAH][Al2Cl7] was investigated and it was found that aromatic methyl-, al- lyl-, and benzyl-ether cleavage is applicable to a variety of heterocyclic compounds. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Kemperman, Gerardus J.,Roeters, Theodorus A.,Hilberink, Peter W.
-
p. 1681 - 1686
(2007/10/03)
-
- Pharmaceutically active compounds
-
The invention relates to a class of tetrahydroisoquinolinylalkanoic acids containing an aryl sulphonamide group which have activity as thromboxane A2 antagonists.
- -
-
-