- Dipeptidyl peptidase-IV inhibitor-aminotetrahydropyrane derivative
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The invention provides a DPPIV inhibitor which has the structure shown as the formula (I) (please see the formula (I) in the description). Experiments show that the inhibitor can effectively inhibit the activity of dipeptidyl peptidase IV (DPPIV) and be used for preventing DPPIV-mediated diseases or delaying progress of the DPPIV-mediated diseases or treating the DPPIV-mediated diseases, particularly 2 type and 1 type diabetes, obesity, arthritis, osteoporosis and part of tumors. The invention further provides a preparation method of the inhibitor.
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Paragraph 0103; 0104; 0105
(2017/07/23)
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- 4,6 DIHYDROPYRROLO [3,4-C] PYRAZOLE-5 (1H)-CARBONITRILE DERIVATES FOR TRATING CANCER
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The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs) and/ or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or
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Page/Page column 57; 65; 75
(2017/10/13)
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- The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors
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Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure-activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease se
- Cox, Jason M.,Chu, Hong D.,Kuethe, Jeffrey T.,Gao, Ying-Duo,Scapin, Giovanna,Eiermann, George,He, Huaibing,Li, Xiaohua,Lyons, Kathryn A.,Metzger, Joseph,Petrov, Aleksandr,Wu, Joseph K.,Xu, Shiyao,Sinha-Roy, Ranabir,Weber, Ann E.,Biftu, Tesfaye
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p. 2622 - 2626
(2016/05/09)
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- (R)- N - [5 - (2 - methoxy - 2 - phenyl-acetyl) - 1, 4, 5, 6 - tetrahydro-pyrrolo [3, 4 - c] pyrazole - 3 - yl] - 4 - (4 - methyl piperazine - 1 - yl) benzamide synthesis method
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The invention belongs to the technical field of medicine and relates to a preparation method for PHA739358(Danusertib), i.e., (R)-N-[5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole-3-yl]-4-(4-methyl piperazine-1-yl)benzamide. According to the invention, altogether four reaction routes are designed, simple and easily available glycine is used as a raw material, reactions like addition, esterification, amino protection and cyclization are carried out so as to prepare (R)-N-[5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole-3-yl]-4-(4-methyl piperazine-1-yl)benzamide, yield of the route 1, 2 and 4 is more than 25%, respectively, and yield of the route 3 is more than 20%. The preparation method has the advantages of a few reaction steps, simple and convenient post-treatment operation, little time consumption, high yield and low total cost. Thus, a novel method is provided for preparation of the antitumor drug PHA739358.
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- Structure-activity-relationship of amide and sulfonamide analogs of omarigliptin
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A series of novel substituted-[(3R)-amino-2-(2,5-difluorophenyl)]tetrahydro-2H-pyran analogs have been prepared and evaluated as potent, selective and orally active DPP-4 inhibitors. These efforts lead to the discovery of a long acting DPP-4 inhibitor, omarigliptin (MK-3102), which recently completed phase III clinical development and has been approved in Japan.
- Chen, Ping,Feng, Dennis,Qian, Xiaoxia,Apgar, James,Wilkening, Robert,Kuethe, Jeffrey T.,Gao, Ying-Duo,Scapin, Giovanna,Cox, Jason,Doss, George,Eiermann, George,He, Huaibing,Li, Xiaohua,Lyons, Kathryn A.,Metzger, Joseph,Petrov, Aleksandr,Wu, Joseph K.,Xu, Shiyao,Weber, Ann E.,Yan, Youwei,Roy, Ranabir Sinha,Biftu, Tesfaye
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p. 5767 - 5771
(2015/11/24)
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- Synthesis and in-vitro antibacterial activity of 7-(3-aminopyrrolo[3,4-c] pyrazol-5(2H,4H,6H)-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives
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A series of novel 7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)-6-fluoro- 4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives was designed, synthesized and characterized by 1H-NMR, MS and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds display rather weak potency against the tested Gram-negative strains, but most of them exhibit good potency in inhibiting the growth of S. aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis including methicillin-resistant S. epidermidis (MRSE) (MIC: 0.125-8 μg/mL). In particular, the compound 9g is 2 to 32 fold more potent than gemifloxacin (GM), moxifloxacin (MX), gatifloxacin (GT), and levofloxacin (LV) against S. pneumoniae 08-3, K. pneumoniae 09-23, and P. aeruginosa ATCC27853, 4 to 32 fold more potent than MX, GM, and LV against K. pneumoniae 09-21, and more active than or comparable to the four reference drugs against P. aeruginosa 09-32. A series of novel fluoroquinolone derivatives was designed and synthesized. All target compounds display rather weak potency against the tested Gram-negative strains, but most of them exhibit good potency in inhibiting the growth of Staphylococcus aureus and Staphylococcus epidermidis. In particular, the compound 9g is the most promising drug.
- Guo, Xin,Bai, Xiao-Guang,Li, Yi-Liang,An, Zhi-Jiao,Xu, Le-Xing,Han, Li-You,Liu, Ming-Liang,Guo, Hui-Yuan,Wang, Yu-Cheng
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p. 523 - 529
(2011/10/30)
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- Design and synthesis of 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and pyrazolo[3,4-b]pyridines for Aurora-A kinase inhibitors
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Two series of 3-aminopyrazole compounds including 24 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and 16 pyrazolo[3,4-b]pyridines were synthesized and evaluated against HCT116, A549, and A2780 tumor cell lines. Among them, three compounds were found to have the ideal anti-proliferative activities in vitro. Docking experiments showed that the novel pyrazolo[3,4-b]pyridines share the similar interaction mode with Aurora-A kinase as PHA739358.
- Shi, Jianyou,Xu, Guobin,Zhu, Wei,Ye, Haoyu,Yang, Shengyong,Luo, Youfu,Han, Jing,Yang, Jincheng,Li, Rui,Wei, Yuquan,Chen, Lijuan
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supporting information; experimental part
p. 4273 - 4278
(2010/09/04)
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- TRICYCLIC HETEROAROMATIC COMPOUNDS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel substituted tricyclic heteroaromatic compounds of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 46-47
(2008/12/05)
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- AMINOCYCLOHEXANES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel substituted aminocyclohexanes of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 37
(2008/06/13)
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- Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition
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Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent c
- Fancelli, Daniele,Berta, Daniela,Bindi, Simona,Cameron, Alexander,Cappella, Paolo,Carpinelli, Patrizia,Catana, Cornel,Forte, Barbara,Giordano, Patrizia,Giorgini, Maria Laura,Mantegani, Sergio,Marsiglio, Aurelio,Meroni, Maurizio,Moll, Juergen,Pittalà, Valeria,Roletto, Fulvia,Severino, Dino,Soncini, Chiara,Storici, Paola,Tonani, Roberto,Varasi, Mario,Vulpetti, Anna,Vianello, Paola
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p. 3080 - 3084
(2007/10/03)
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- Bicyclo-pyrazoles active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
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Bicyclo-pyrazole compounds of formula (I), as herein defined, are useful for treating diseases linked to disregulated protein kinases.
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