- Synthesis and tunable ion-recognition properties of novel macrocyclic triamides
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In this work, we report synthesis of rigid macrocyclic triamides and their tunable ion-recognition properties as selective anion and metal receptors. Diphenylacetylene-containing cyclic triamide CTA-1b and three cyclic triamides bearing functional methoxy
- Ge, Ziyi,Zhang, Xingye,Chen, Shaojie,Liu, Ying,Peng, Ruixiang,Yokazawa, Tsutomu
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- INHIBITORS OF HEPATITIS C VIRUS REPLICATION
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The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.
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Paragraph 0678-0679
(2019/05/15)
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- cGAS ANTAGONIST COMPOUNDS
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Disclosed are novel compounds of Formula (I) that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.
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Paragraph 0267
(2017/11/06)
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- NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
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This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.
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Page/Page column 96; 97
(2016/04/20)
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- Orally Bioavailable Metal Chelators and Radical Scavengers: Multifunctional Antioxidants for the Coadjutant Treatment of Neurodegenerative Diseases
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Neurodegenerative diseases are associated with oxidative stress that is induced by the presence of reactive oxygen species and the abnormal cellular accumulation of transition metals. Here, a new series of orally bioavailable multifunctional antioxidants (MFAO-2s) possessing a 2-diacetylamino-5-hydroxypyrimidine moiety is described. These MFAO-2s demonstrate both free radical and metal attenuating properties that are similar to the original published MFAO-1s that are based on 1-N,N′-dimethylsulfamoyl-1-4-(2-pyrimidyl)piperazine. Oral bioavailability studies in C57BL/6 mice demonstrate that the MFAO-2s accumulate in the brain at significantly higher levels than the MFAO-1s while achieving similar neural retina levels. The MFAO-2s protect human neuroblastoma and retinal pigmented epithelial cells against hydroxyl radicals in a dose-dependent manner by maintaining cell viability and intracellular glutathione levels. The MFAO-2s outperform clioquinol, a metal attenuator that has been investigated for the treatment of Alzheimer's disease.
- Kawada, Hiroyoshi,Kador, Peter F.
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p. 8796 - 8805
(2015/12/09)
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- NEUROPROTECTIVE MULTIFUNCTIONAL ANTIOXIDANTS AND THEIR MONOFUNCTIONAL ANALOGS
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The neuroprotective multifunctional antioxidants are compounds that contain a 2-diacetylamino-5-hydroxypyrimidine moiety, having the structural formula: wherein R1 is CH2 or C2H4; R2 is H or —OR4 where R4 is H or aryl; and R3a and R3b are independently selected from the group consisting of H and —O-alkyl. The antioxidants are orally bioavailable metal-attenuating multifunctional antioxidants that can independently attenuate transition metals, as well as scavenger free radicals. The multifunctional antioxidant compounds, by their ability to independently chelate metals, such as Fe, Cu or Zn, and scavenge free radicals generated from different sources, are neuroprotective and are beneficial for the treatment of various neurological disorders, such as Alzheimer's disease, Parkinson's disease, ALS, traumatic brain injury, ocular disorders, such as cataract, glaucoma, age-related macular degeneration and other retinal degeneration, as well as for reducing the progression of diabetic complications.
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Paragraph 0093
(2014/09/03)
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- HETEROCYCLIC AMINO BERBAMINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF
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The present invention relates to a novel berbamine derivative of formula I or a pharmaceutically acceptable salt thereof, a process for preparation of the same, a pharmaceutical composition comprising said compound and its use in manufacture of an antitumor medicament.
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Paragraph 0091
(2013/07/25)
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- HETEROCYCLIC AMINOBERBAMINE DERIVATIVES, THE PREPARATION PROCESS AND USE THEREOF
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The present invention relates to a novel berbamine derivative of formula I or a pharmaceutically acceptable salt thereof, a process for preparation of the same, a pharmaceutical composition comprising said compound and its use in manufacture of an antitumor medicament.
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Paragraph 0098
(2013/07/19)
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- PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY
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Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazoles of Formula I, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.
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Page/Page column 56
(2011/02/15)
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- N -pyridyl and pyrimidine benzamides as KCNQ2/Q3 potassium channel openers for the treatment of epilepsy
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A series of N-pyridyl benzamide KCNQ2/Q3 potassium channel openers were identified and found to be active in animal models of epilepsy and pain. The best compound 12 [ICA-027243, N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide] has an EC50 of 0.38 μM and is selective for KCNQ2/Q3 channels. This compound was active in several rodent models of epilepsy and pain but upon repeated dosing had a number of unacceptable toxicities that prevented further development. On the basis of the structure-activity relationships developed around 12, a second compound, 51, [N-(2-chloro-pyrimidin-5-yl)-3,4-difluoro- benzamide, ICA-069673], was prepared and advanced into a phase 1 clinical study. Herein, we describe the structure-activity relationships that led to the identification of compound 12 and to the corresponding pyrimidine 51.
- Amato, George,Roeloffs, Rosemarie,Rigdon, Greg C.,Antonio, Brett,Mersch, Theresa,McNaughton-Smith, Grant,Wickenden, Alan D.,Fritch, Paul,Suto, Mark J.
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supporting information; experimental part
p. 481 - 484
(2011/08/22)
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- Multifunctional antioxidants for the treatment of age-related diseases
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Analogues of N,N-dimethyl-4-(pyrimidin-2-yl)piperazine-1-sulfonamide possessing a free radical scavenger group (FRS), chelating groups (CHL), or both (FRS + CHL) have been synthesized. Electrospray ionization mass spectrometry studies indicate that select
- Jin, Hongxia,Randazzo, James,Zhang, Peng,Kador, Peter F.
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scheme or table
p. 1117 - 1127
(2010/08/05)
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- INHIBITORS OF HEPATITIS C VIRUS REPLICATION
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The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.
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Page/Page column 98
(2010/11/04)
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- COMPOUNDS, COMPOSITIONS AND METHODS
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Compounds, compositions, and methods for treating fungal infection by modulating the activity of the fungal kinesin Kip 1 are disclosed.
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- Pyrimidines as novel openers of potassium ion channels
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The present invention provides a genus of pyrimidine amides that are useful as openers of potassium ion channels. The compounds of the invention are of use in both therapeutic and diagnostic methods.
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