- PURINONE COMPOUNDS AND THEIR USE IN TREATING CANCER
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The specification generally relates to compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, where R1, A1, A2 and A3 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent DNA-PK mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating DNA-PK mediated disease, including cancer, using such compounds and salts.
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Page/Page column 39; 43
(2020/01/08)
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- A new and improved process for C-aryl glucoside SGLT2 inhibitors
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A practical and scalable synthesis of C-glycosides identified as highly potent sodium-dependent glucose transporter 2 (SGLT2) inhibitors is described. Highlights of the synthetic process are a concise, ten-step synthesis of a structurally complex active pharmaceutical ingredient from a known intermediate via a selective and quantitative addition of an aryl species to the Weinreb amide, and the isomers of undesired ortho-products were avoided during the preparation. The chemistry developed has been applied to prepare SGLT2 inhibitors without recourse to chromatography.
- Liu, Yonghai,Fu, Tingming,Chen, Zhidong,Ou, Chunyan
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p. 1715 - 1721
(2015/09/15)
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- Pyrano[3,2-c]benzopyran-6(2h)-one derivatives and uses thereof
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The present invention relates to new pyrano[3,2-c]benzopyran-6(2H)-one derivatives that act as SGLT2 inhibitors, which makes them promising candidates for the treatment of diabetes and other diseases and conditions mediated by SGLT2. These new drugs also exhibit platelet aggregation inhibitory activity which makes them promising candidates in the treatment and/or prevention of prothrombotic conditions. The invention also relates to the use of such pyrano[3,2-c]benzopyran-6(2H)-one derivatives in the treatment or prevention of the diabetes and other disorders and conditions mediated by SGLT2, as a single active ingredient or in combination with another antidiabetic agent or a drug for the treatment of hypertension, chronic heart failure or atherosclerosis, and pharmaceutical compositions comprising said new pyrano[3,2-c]benzopyran-6(2H)-one derivatives.
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Paragraph 0116; 0117
(2013/04/10)
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- PYRANO[3,2-c][2]BENZOPYRAN-6(2H)-ONE DERIVATIVES AND USES THEREOF
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The present invention relates to new pyrano[3,2-c][2]benzopyran-6(2H)-one derivatives that act as SGLT2 inhibitors, which makes them promising candidates for the treatment of diabetes and other diseases and conditions mediated by SGLT2. These new drugs also exhibit platelet aggregation inhibitory activity which makes them promising candidates in the treatment and/or prevention of prothrombotic conditions. The invention also relates to the use of such pyrano[3,2-c][2]benzopyran-6(2W)-one derivatives in the treatment or prevention of the diabetes and other disorders and conditions mediated by SGLT2, as a single active ingredient or in combination with another antidiabetic agent or a drug for the treatment of hypertension, chronic heart failure or atherosclerosis, and pharmaceutical compositions comprising said new pyrano[3,2-c][2]benzopyran-6(2H)-one derivatives.
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Page/Page column 41
(2013/04/13)
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- BORON-CONTAINING SMALL MOLECULES
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This invention provides novel compounds, methods of using the compounds, and pharmaceutical compositions containing the compounds.
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Paragraph 0380; 0581
(2013/06/04)
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- Improved preparation of (1S,3′R,4′S,5′S,6′R)-5- chloro-6-[(4-ethylphenyl)methyl]-3′,4′,5′,6′-tetrahydro- 6′-(hydroxymethyl)-spiro[isobenzofuran-1(3H),2′-[2H]pyran]-3′, 4′,5′-triol
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A convenient approach for the preparation of (1S,3′R,4′S, 5′S,6′R)-5-chloro-6-[(4-ethylphenyl)methyl]-3′,4′, 5′,6′-tetrahydro-6′-(hydroxymethyl)-spiro[isobenzofuran-1(3H), 2′-[2H]pyran]-3′,4′,5′-triol is developed. The targeted compound was synthesized from 2-bromo-4-methylbenzoic acid in nine steps and the isomers of undesired ortho-products were avoided during the preparation.
- Liu, Yong-Hai,Fu, Ting-Ming,Ou, Chun-Yan,Fan, Wen-Ling,Peng, Guo-Ping
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p. 131 - 133
(2013/06/26)
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- Thiazolylmethyl ortho-substituted phenyl glucoside library as novel C-aryl glucoside SGLT2 inhibitors
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In order to investigate SAR regarding proximal phenyl ring in novel C-aryl glucoside SGLT2 inhibitors containing a thiazole motif, a series of chemical modifications on proximal phenyl ring was conducted. During a series of lead optimization efforts, orth
- Lee, Suk Ho,Kim, Min Ju,Lee, Sung-Han,Kim, Jeongmin,Park, Hyun-Ju,Lee, Jinhwa
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experimental part
p. 2662 - 2675
(2011/07/08)
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- THIAZOLE DERIVATIVES AS SGLT2 INHIBITORS AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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The present invention relates to a novel compound with thiazole ring having an inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) being present in the intestine and kidney, and a pharmaceutical composition comprising the same as an active ingredient, which is useful for preventing or treating metabolic disorders, particularly diabetes.
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Page/Page column 28
(2012/01/06)
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- Conformationally constrained spiro C-arylglucosides as potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors
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(Chemical Equation Presented) Sodium glucose co-transporter 2 (SGLT2) is an emerging target for the treatment of type 2 diabetes mellitus (DM2). Here, the synthesis and preliminary biological evaluation of a series of potent, selective SGLT2 inhibitors, derived from a rigid spiro C-arylglucoside scaffold, is described.
- Lv, Binhua,Feng, Yan,Dong, Jiajia,Xu, Min,Xu, Baihua,Zhang, Wenbin,Sheng, Zelin,Welihinda, Ajith,Seed, Brian,Chen, Yuanwei
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scheme or table
p. 827 - 831
(2011/02/22)
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- O-Spiro C-aryl glucosides as novel sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors
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Two series of O-spiro C-aryl glucosides were synthesized and tested for inhibition of hSGLT1 and hSGLT2. 6′-O-Spiro C-aryl glucosides exhibited potent in vitro hSGLT2 inhibitory activity but 2′-O-spiro C-aryl glucosides showed no in vitro hSGLT2 inhibitory activity at a screening concentration of 1 μM.
- Xu, Baihua,Lv, Binhua,Feng, Yan,Xu, Ge,Du, Jiyan,Welihinda, Ajith,Sheng, Zelin,Seed, Brian,Chen, Yuanwei
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scheme or table
p. 5632 - 5635
(2010/04/05)
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- Exploration of O-spiroketal C-arylglucosides as novel and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors
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A series of novel O-spiroketal C-arylglucosides have been prepared and evaluated in cell-based functional assays for activity against human sodium-dependent glucose co-transporters 1 and 2 (SGLT1 and 2). The core spiro[isobenzofuran-1,2′-pyran] structure proved to be an effective scaffold for diversification and a number of compounds with single digit nanomolar potency and high selectivity have been synthesized. Compound 5a promoted glucosuria when administered in vivo in rats and produced a significant blood glucose reduction effect.
- Lv, Binhua,Xu, Baihua,Feng, Yan,Peng, Kun,Xu, Ge,Du, Jiyan,Zhang, Lili,Zhang, Wenbin,Zhang, Ting,Zhu, Liangcheng,Ding, Haifeng,Sheng, Zelin,Welihinda, Ajith,Seed, Brian,Chen, Yuanwei
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scheme or table
p. 6877 - 6881
(2010/05/19)
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- BENZYLIC GLYCOSIDE DERIVATIVES AND METHODS OF USE
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Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT inhibition.
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Page/Page column 15
(2008/12/07)
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- GLUCOSE TRANSPORT INHIBITORS AND METHODS OF USE
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Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT inhibition.
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Page/Page column 19
(2008/06/13)
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- Methods of making 6-[(4,5-Dihydro-1H-imidazol-2-yl)amino-]-7-methyl-1H-benzimidazole-4-carbonitrile and its preferred salt form
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6-[(4,5-Dihydro-1H-imidazol-2-yl)amino-]-7-methyl-1H-benzimidazole-4-carbonitrile substantially free of 2,3,7-triamino-4,6-dimethyl-1,9-phenazinedicarbonitrile, and the anhydrous monoacetate salt thereof, are useful in the treatment of alpha-2 mediated di
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