- A sensitive method for the determination of gold and palladium based on dispersive liquid-liquid microextraction combined with flame atomic absorption spectrometric determination using: N -(6-morpholin-4-ylpyridin-3-yl)- N ′-phenylthiourea
-
A new method for the determination of gold and palladium was developed by dispersive liquid-liquid microextraction separation-preconcentration and flame atomic absorption spectrometry detection. In the proposed approach, N-(6-morpholin-4-ylpyridin-3-yl)-N′-phenylthiourea (MPPT) was synthesized as a complexing agent. The complexation ability of the MPPT was explored by examining the effect of a series of heavy metal ions, including Mn2+, Pd2+, Ni2+, Cd2+, Co2+, Cu2+, Au3+, Pb2+, Zn2+ and Fe3+, using the DLLME procedure. The MPPT exhibited pronounced selectivity toward Pd2+ and Au3+ ions at different pH levels. Factors influencing the extraction efficiency and complex formation were examined, i.e. the pH of the sample solution, the concentration of the chelating agent, the extraction and dispersive solvent type and volume, the sample volume, and foreign ions, etc. Optimal conditions for quantitative recoveries were pH 5.5 for gold and pH 1.5 for palladium, 125 μL of % 0.4 MPPT, 1200 μL of methanol and 125 μL of carbon tetrachloride. The presented method showed a good linearity within a range of 30-230 and 25-200 μg L-1 with the detection limits of 1.75 and 1.65 μg L-1 for Au and Pd, respectively. The relative standard deviation (RSD) was below 2.8% at 50 μg L-1 for both ions (n = 10). The developed method was simple, fast, cost efficient, and sensitive for the extraction and preconcentration of gold and palladium in samples of liquids (sea, stream water) and solids (stream sediment, ores, and electronic waste).
- Bahadir, Zekeriyya,Bulut, Volkan Numan,Bekta?, Hakan,Soylak, Mustafa
-
-
Read Online
- Synthesis, Antibacterial and Anthelmintic Activity of Novel 3-(3-Pyridyl)-oxazolidinone-5-methyl Ester Derivatives
-
In this study, a series of 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives was synthesized and characterized by1H NMR,13C NMR, and LC-MS. The conducted screening antibacterial studies of the new 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives established that the methyl sulfonic acid esters have broad activity spectrum towards Staphylococcus aureus, Streptococcus pneu-moniae, Bacillus subtilis and Staphylococcus epidermidis. Among them, compound 12e has the most potent activity, with an MIC of 16 μg/mL against B.subtilis, and could reduce the instantaneous growth rate of bacteria. Furthermore, molecular docking studies were also simulated for compound 12e to predict the specific binding mode of this compound. In addition, anthelmintic activity of these compounds was also evaluated against adult Indian earthworms (Pheretima posthuman). The results showed that compound 11b had the best effect. These results above can provide experimental ref-erence for the development of novel antibacterial and anthelmintic drugs.
- Chen, Jia-Yi,Jin, Bo,Sheng, Zun-Lai,Sun, Meng-Qing,Yang, Hong-Liang
-
-
- FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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The present disclosure relates to a class of fused pyrimidine compounds of Formula I, their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to a process of preparation of these fused pyrimidine compounds, and to pharmaceutical compositions containing them.
- -
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Paragraph 0233
(2021/04/02)
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- BENZIMIDAZOLE AND HYDROGENATED CARBAZOLE DERIVATIVES AS GPX4 INHIBITORS
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This present disclosure relates to compounds with ferroptosis inducing activity, a method of treating a subject with cancer with the compounds, and combination treatments with a second therapeutic agent.
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Page/Page column 57-58
(2021/03/05)
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- MALT1 INHIBITORS AND USES THEREOF
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The invention provides compounds of formula (I) wherein R1, R2, R3, R4 and R5 are as defined in the specification which are potent inhibitors of the enzyme MALT1 and are useful in the treatment of autoimmune disorders and diseases and as an immunooncology approach to the treatment of cancer, especially bladder cancer, colon cancer, hepatocellular cancer and small cell or non-small cell lung cancer.
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Page/Page column 74
(2021/10/15)
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- COMPOUNDS AND METHOD FOR TREATING CYTOKINE RELEASE SYNDROME
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Disclosed herein are embodiments of a method for treating or preventing cytokine release syndrome (CRS). In certain embodiments, the method comprises administering a compound, or a salt, solvate, prodrug or pharmaceutical composition thereof, to a subject experiencing, or at risk of developing, CRS. The compound may be a kinase inhibitor, such as a JAK inhibitor and/or an IRAK inhibitor, and/or the compound may have a structure according to Formulas I, III, IV or VII. And the method may comprise administering the compound to a subject who is has received, is currently receiving, and/or will be receiving a cell therapy.
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Page/Page column 132
(2021/02/12)
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- C-TERMINAL SRC KINASE INHIBITORS
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Provided herein are novel C-terminal Srk Kinase (CSK) inhibitors, e.g., having Formula G, I, II, or III. Also provided are methods of preparing the novel CSK inhibitors and method of using the novel CSK inhibitors for treating diseases or disorder such as cancer or for promoting immune response in a subject in need thereof. (G)
- -
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Paragraph 147
(2020/07/14)
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- First-in-class DAPK1/CSF1R dual inhibitors: Discovery of 3,5-dimethoxy-N-(4-(4-methoxyphenoxy)-2-((6-morpholinopyridin-3-yl)amino)pyrimidin-5-yl)benzamide as a potential anti-tauopathies agent
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Kinase irregularity has been correlated with several complex neurodegenerative tauopathies. Development of selective inhibitors of these kinases might afford promising anti-tauopathy therapies. While DAPK1 inhibitors halt the formation of tau aggregates and counteract neuronal death, CSF1R inhibitors could alleviate the tauopathies-associated neuroinflammation. Herein, we report the design, synthesis, biological evaluation, mechanistic study, and molecular docking study of novel CSF1R/DAPK1 dual inhibitors as multifunctional molecules inhibiting the formation of tau aggregates and neuroinflammation. Compound 3l, the most potent DAPK1 inhibitor in the in vitro kinase assay (IC50 = 1.25 μM) was the most effective tau aggregates formation inhibitor in the cellular assay (IC50 = 5.0 μM). Also, compound 3l elicited potent inhibition of CSF1R in the in vitro kinase assay (IC50 = 0.15 μM) and promising inhibition of nitric oxide production in LPS-induced BV-2 cells (55% inhibition at 10 μM concentration). Kinase profiling and hERG binding assay anticipated the absence of off-target toxicities while the PAMPA-BBB assay predicted potentially high BBB permeability. The mechanistic study and selectivity profile suggest compound 3l as a non-ATP-competitive DAPK1 inhibitor and an ATP-competitive CSF1R inhibitor while the in silico calculations illustrated binding of compound 3l to the substrate-binding site of DAPK1. Hence, compound 3l might act as a protein-protein interaction inhibitor by hindering DAPK1 kinase reaction through preventing the binding of DAPK1 substrates.
- Farag, Ahmed Karam,Hassan, Ahmed H.E.,Jeong, Hyeanjeong,Kwon, Youngji,Choi, Jin Gyu,Oh, Myung Sook,Park, Ki Duk,Kim, Yun Kyung,Roh, Eun Joo
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p. 161 - 175
(2018/11/23)
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- N-heteroarylsulfonamide derivative, and preparation and application of same
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The invention provides an N-heteroarylsulfonamide derivative, and preparation and an application of same. The derivative includes pharmaceutically acceptable salts and solvates thereof; a test provesthat the N-heteroarylsulfonamide derivative allows specific combination and inhibit or reduce the activity of potassium pathway Kv1.3, so that the derivative can be used for treating autoimmune diseases, caused by abnormal activation of the potassium pathway Kv1.3, of human or animal. An inhibitor in the invention also includes a medicinal composition of the compound. The invention also provides amethod for preparing the compound. The derivative has the general formula as the specification.
- -
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Paragraph 0128; 0129-0131; 0135
(2019/05/15)
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- NOVEL FUSED PYRIDINE DERIVATIVES USEFUL AS FAK/AURORA KINASE INHIBITORS
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This invention relates to certain novel pyrimidine derivatives of the Formula (I). The invention also relates to process for the preparation of the compound of the formula (I), pharmaceutical agents or compositions containing the compound or a method of using the compound for the treatment of proliferative diseases, such as cancer.
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Page/Page column 39; 40
(2018/02/28)
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- Design, synthesis and biological evaluation N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives bearing acylamino or DBTD ‘head’ as potential ALK inhibitors
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Aiming to develop promising ALK inhibitors, two series of N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives (22a-x and 23a-d) were designed according to scaffold hopping and bioisosterism principles. All compounds were efficiently synthesized by concise reactions and anti-proliferative activities on ALK-addicted H2228, Karpas299 cells and EGFR-expressive A549 cell were evaluated by MTT assay. Several compounds exhibited potential cytotoxic activities with IC50 values below 0.10 μM. Five compounds (22g, 22h, 22l, 22s and 23a) were selected for further enzymatic determination, resulting in the discovery of 22l against ALK and ALKL1196M with IC50 values of 2.1 nM and 3.8 nM. Particularly, western blot and cell apoptosis assays identified 22l as a promising ALK inhibitor, which was capable of obviously inhibiting cellular ALK activity and inducing cell apoptosis. Eventually, molecular docking modes of 22l with ALK confirmed structural basis in accordance with the SARs analysis.
- Xing, Lingyun,Jing, Tongfei,Zhang, Junlong,Guo, Ming,Miao, Xiuqi,Jiang, Feng,Zhai, Xin
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p. 689 - 699
(2018/10/02)
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- NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS
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The invention relates to the field of medicine, discloses new nitrogen heterocyclic derivatives, preparation method thereof and as medicament in particular as the treatment and prevention of treating tissue fibrosis of the medicament. The invention also discloses a pharmaceutically acceptable compound of the present invention comprise a pharmaceutical composition and methods for using the composition for the treatment of the human or animal tissue fibrosis of diseases, in particular for treating the human or animal renal interstitial fibrosis, glomerular sclerosis, hepatic fibrosis, pulmonary fibrosis, peritoneal fibrosis, myocardial fibrosis, skin fibrosis, after the operation of adhering, benign prostate hypertrophy, bone-myocardial, scleroderma, multiple sclerosis, pancreas fibrosis, liver cirrhosis, myosarcoma, neurofibromatosis, interstitial pulmonary fibrosis, diabetic nephropathy, Alzheimer's disease or vascular fibrosis disease in use. (by machine translation)
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Page/Page column 144
(2018/06/01)
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- Design, synthesis, and biological evaluation of structurally modified isoindolinone and quinazolinone derivatives as hedgehog pathway inhibitors
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The Hedgehog (Hh) signaling pathway is associated with diverse aspects of cellular events, such as cell migration, proliferation, and differentiation throughout embryonic development and tissue patterning. An abnormal Hh signaling pathway is linked to numerous human cancers, including basal cell carcinoma (BCC), medulloblastoma (MB), lung cancer, prostate cancer, and ovarian cancer, and it is therefore a promising target in cancer therapy. Using a structure-hopping approach, we designed new Hh signaling pathway inhibitors with isoindolinone or quinazolinone moieties, which were synthesized and biologically evaluated using an 8xGli-luciferase (Gli-Luc) reporter assay in NIH3T3 cells. Compounds 9–11 and 14 with isoindolinone scaffolds demonstrated moderate Hh inhibitory activity; whereas quinazolinone derivatives 24, 29, 32, 34, and 35 exhibited good potency with submicromolar IC50values and the analog 28 showed nanomolar IC50value. Although sonidegib shows a decrease in inhibitory effect on vismodegib resistance-conferring Smo mutants, the structurally modified new compounds not only possess the pharmacophoric properties of Hh pathway inhibition but also preserve the suppressive potency in drug-resistant Smo mutants. Mechanistically, quinazolinone derivatives 28 and 34 suppress Hh signaling by blocking Smo and Gli translocation into the cilia, similar to vismodegib and sonidegib. Additionally, the human microsomal stability of the representative analogs 28 and 34 were determined to be comparable to that of the reference compound sonidegib. Thus, these new scaffolds can serve as a platform for the development of novel cancer therapeutics targeting the Hh pathway.
- Bhattarai, Deepak,Jung, Joo Hyun,Han, Seunghyeon,Lee, Hankyu,Oh, Soo Jin,Ko, Hyuk Wan,Lee, Kyeong
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p. 1036 - 1050
(2016/11/11)
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- New pyridine derivatives as antiurease inhibitors: Synthesis and their evaluation for antimicrobial activities
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6-Morpholin-4-ylpyridin-3-amine (3) gathered starting from morpholine by two steps was converted into the corresponding arylidenehydrazides through the reaction with several aromatic aldehydes. The treatment of compound 3 with phenylisothiocy-anate generated N-(6-morpholin-4-ylpyridin-3-yl)-N'-phenylthio-urea (6). The synthesis of 1,3-thiazolidine (7) and 1,3-thiazole derivatives was performed from the reaction of 6 with 4-chlorophenacyl bromide and ethyl bromoacetate, respectively. All synthesized compounds were inspected for their antimicrobial and antiurease activites. (Chemical Equation Presented).
- Bektas, Hakan,Albay, Canan,Mentese, Emre,Demirbas, Neslihan
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p. 199 - 205
(2017/07/22)
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- Discovery of novel dual inhibitors of VEGFR and PI3K kinases containing 2-ureidothiazole scaffold
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A series of compounds possessing 2-(3-phenyl)ureidothiazol-4-formamide derivatives with a 2-ureidothiazole scaffold were designed and synthesized. Some compounds demonstrated inhibition of cell proliferation against both MDA-MB-231 and HepG2 cell lines using Sorafenib as the positive control. Compounds 6i showed a good to moderate inhibition on VEGFR-2 and PI3Kα which was proved by further molecular docking study. This study suggests that compound 6i is a potential dual inhibitor of VEGFR-2 and PI3Kα and is applicable for further investigation.
- Li, Lin,Zhang, Cun-Long,Song, Hong-Rui,Tan, Chun-Yan,Ding, Huai-Wei,Jiang, Yu-Yang
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supporting information
p. 1 - 6
(2016/01/25)
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- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
- -
-
Paragraph 00980; 00981
(2015/09/28)
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- Nitrogenous Heterocyclic Derivatives And Their Application In Drugs
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The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.
- -
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Paragraph 0637
(2015/03/31)
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- Synthesis and antiproliferative activity of novel 4-substituted-phenoxy-benzamide derivatives
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A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibited moderate efficacy in HT29 and MGC803 cell lines. Compound 10c showed promising inhibition of hedgehog (Hh) signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.
- Sun, Chi-Yu,Li, Yang-Sheng,Shi, Ai-Long,Li, Ya-Fei,Cao, Rui-Fang,Ding, Huai-Wei,Yin, Qing-Qing,Zhang, Li-Juan,Zheng, Hua-Chuan,Song, Hong-Rui
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supporting information
p. 1307 - 1310
(2015/12/31)
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- Five-And-Six-Membered Heterocyclic Compound, And Preparation Method, Pharmaceutical Composition And Use Thereof
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A five-and-six-membered heterocyclic compound as represented by general formula I, pharmaceutically acceptable salt, metabolite, metabolic precursors or drug precursors thereof, preparation method, pharmaceutical composition, and use thereof; the five-and-six-membered heterocyclic compound has activity as a Janus kinase (JAK) inhibitor, and can be used to prepare drugs for treating diseases caused by the abnormal activity of kinase, such as cell proliferation diseases like cancer.
- -
-
Paragraph 0391; 0392
(2015/12/07)
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- NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS
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The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.
- -
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Paragraph 00354
(2014/02/15)
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- TRI-HETEROCYCLIC DERIVATIVES, PREPARATION PROCESS AND USES THEREOF
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The present invention relates to a tri-heterocyclic derivatives, preparation process and uses thereof, specifically relates to a tri-heterocyclic derivatives of the formula (I) or a pharmaceutically acceptable salt thereof, preparation process, and further relates to a pharmaceutically acceptable composition comprising compounds of formula (I), or a pharmaceutically acceptable salt thereof, and their pharmaceutical use as inhibitors of kinase.
- -
-
Paragraph 0124; 0318; 0319
(2014/11/13)
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- Amination of heteroaryl chlorides: Palladium catalysis or SNAr in green solvents?
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The reaction of heteroaryl chlorides in the pyrimidine, pyrazine and quinazoline series with amines in water in the presence of KF results in a facile SNAr reaction and N-arylation. The reaction is less satisfactory with pyridines unless an add
- Walsh, Katie,Sneddon, Helen F.,Moody, Christopher J.
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p. 1455 - 1460
(2013/09/12)
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- SULFONAMIDE COMPOUNDS AND USES AS TNAP INHIBITORS
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Described herein are compounds that modulate the activity of TNAP. In some embodiments, the compounds described herein inhibit TNAP. In certain embodiments, the compounds described herein are useful in the treatment of conditions associated with hyper- mineralization.
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Paragraph 00642
(2013/09/12)
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- TRI-HETEROCYCLIC DERIVATIVES, PREPARATION PROCESS AND USES THEREOF
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The present invention relates to a tri-heterocyclic derivatives, preparation process and uses thereof, specifically relates to a tri-heterocyclic derivatives of the formula (I) or a pharmaceutically acceptable salt thereof, preparation process, and further relates to a pharmaceutically acceptable composition comprising compounds of formula (I), or a pharmaceutically acceptable salt thereof, and their pharmaceutical use as inhibitors of kinase
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Page/Page column 27
(2013/07/05)
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- Synthesis and cytotoxic activity of some novel N-pyridinyl-2-(6- phenylimidazo[2,1-b]thiazol-3-yl)acetamide derivatives
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A series of novel compounds bearing imidazo[2,1-b]thiazole scaffolds were designed and synthesized based on the optimization of the virtual screening hit compound N-(6-morpholinopyridin-3-yl)-2-(6-phenylimidazo[2,1-b]thiazol-3-yl) acetamide (5a), and tested for their cytotoxicity against human cancer cell lines, including HepG2 and MDA-MB-231. The results indicated that the compound 2-(6-(4-chlorophenyl)imidazo [2,1-b]thiazol-3-yl)-N-(6-(4-(4-methoxybenzyl) piperazin-1-yl)pyridin-3-yl)acetamide (5l), with slightly higher inhibition on VEGFR2 than 5a (5.72% and 3.76% inhibitory rate at 20 μM, respectively), was a potential inhibitor against MDA-MB-231 (IC50 = 1.4 μM) compared with sorafenib (IC50 = 5.2 μM), and showed more selectivity against MDA-MB-231 than HepG2 cell line (IC50 = 22.6 μM).
- Ding, Huaiwei,Chen, Zhe,Zhang, Cunlong,Xin, Tian,Wang, Yini,Song, Hongrui,Jiang, Yuyang,Chen, Yuzong,Xu, Yongnan,Tan, Chunyan
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experimental part
p. 4703 - 4716
(2012/07/01)
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- Nitrosation of aryl and heteroaryltrifluoroborates with nitrosonium tetrafluoroborate
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Organotrifluoroborates have emerged as an alternative to toxic and air- and moisture-sensitive organometallic species for the synthesis of functionalized aryl and heteroaryl compounds. It has been shown that the trifluoroborate moiety can be easily converted into a variety of different substituents in a late synthetic stage. In this paper, we disclose a mild, selective, and convenient method for the ipso-nitrosation of organotrifluoroborates using nitrosonium tetrafluoroborate (NOBF4). Aryl- and heteroaryltrifluoroborates were converted into the corresponding nitroso products in good to excellent yields. This method proved to be tolerant of a broad range of functional groups.
- Molander, Gary A.,Cavalcanti, Livia N.
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experimental part
p. 4402 - 4413
(2012/06/18)
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- Discovery and optimization of 2-phenyloxazole derivatives as diacylglycerol acyltransferase-1 inhibitors
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In a discovery effort to find safe and effective DGAT-1 inhibitors, we have identified 2-phenyloxazole 4-carboxamide 1 as a conformationally constrained analog of a hydrazide hit, which was previously identified from high-throughput screening. Further optimization of this series has led to chemically more stable 2-phenyloxazole-based DGAT-1 inhibitor 25 with improved solubility, cell-based activity, and pharmacokinetic properties. Compound 25 also demonstrated in vivo efficacy in a diet-induced obesity (DIO) rat model.
- Yun, Weiya,Ahmad, Mushtaq,Chen, Yingsi,Gillespie, Paul,Conde-Knape, Karin,Kazmer, Sonja,Li, Shiming,Qian, Yimin,Taub, Rebecca,Wertheimer, Stanley J.,Whittard, Toni,Bolin, David
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scheme or table
p. 7205 - 7209
(2012/01/15)
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- Synthesis and aminolysis of 2,4-dinitrophenyl and 5-nitropyridine N-hydroxy oxime derivatives
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The 2,4-dinitrophenoxy derivatives 12-16 and the 5-nitro-2-pyridyloxy derivatives 18-22 were prepared. The products were identified by elemental analysis, IR, and NMR. The reaction of 12-16 and 18-22 with morpholine as nucleophile in CH3CN occu
- Khattab, Sherine N.,Hamed, Ezzat Awad,Albericio, Fernando,El-Faham, Ayman
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p. 633 - 639
(2011/08/06)
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- Synthesis and solid state study of pyridine- and pyrimidine-based fragment libraries
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A library of pyridines and pyrimidines has been synthesised in excellent yields employing microwave and flow chemistry methodologies. Work-up bottlenecks have been facilitated substantially by the use of supported reagents and many of the final compounds have been studied in the solid state by single crystal X-ray diffraction.
- Spencer, John,Patel, Hiren,Callear, Samantha K.,Coles, Simon J.,Deadman, John J.
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scheme or table
p. 5905 - 5909
(2011/11/14)
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- THIAZOLE SULFONAMIDE AND OXAZOLE SULFONAMIDE KINASE INHIBITORS
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The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents
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Page/Page column 105-106
(2010/10/03)
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- COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY
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Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful.
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Page/Page column 85
(2010/08/07)
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- Anti-Viral Compounds
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Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.
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Paragraph 0128; 0129-0131; 0135
(2010/12/29)
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- SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS AS KINASE INHIBITOR COMPOUNDS
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Pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.
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Page/Page column 35
(2010/01/12)
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- THIAZOLE AND OXAZOLE KINASE INHIBITORS
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The present invention provides thiazole and oxazole compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
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Page/Page column 147
(2009/04/25)
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- THIAZOLE AND OXAZOLE KINASE INHIBITORS
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The present invention provides thiazole and oxazole compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
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Page/Page column 237
(2009/07/17)
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- Diacylglycerol acyltransferase inhibitors
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.
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Page/Page column 12
(2010/11/27)
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- C-N bond formation by the oxidative alkylamination of azines: Comparison of AgPy2MnO4 versus KMnO4 as oxidant
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Reports on the successful oxidative alkylamination of azines by the S NH-reaction, with the use of alkylamines other than methylamine, are very scarce. Hitherto, the experimental limitation to extend oxidative animation of azines wit
- Gulevskaya, Anna V.,Maes, Bert U. W.,Meyers, Caroline,Herrebout, Wouter A.,Van Der Veken, Benjamin J.
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p. 5305 - 5314
(2007/10/03)
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- Research and development of an efficient process for the construction of the 2,4,5-substituted pyridines of NK-1 receptor antagonists
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Roche has identified a 2,4,5-trisubstituted pyridine template for a new class of potent NK1 receptor antagonists. Previous strategies for construction of the pyridine core of these NK-1 receptor antagonists involved functionalization of a 2,5-disubstituted pyridine. We now report on construction of the pyridine core from commodity components. Shestopalov reported the synthesis of trans-4′-aryl-5′-cyano-1′,2′,3′, 4′-tetrahydro-6′-hydroxy-2′-oxo-1,3′-bipyridinium inner salts from 1-(2-amino-2-oxo-ethyl)pyridinium chloride, aromatic aldehydes, and ethyl cyanoacetate in the presence of a base. Reaction of these salts with phosphorus oxychloride affords 4-aryl-3-cyano-2,6-dichloropyridines. These are efficiently converted to nicotinamide precursors of the Roche NK-1 receptor antagonists by regioselective displacement of one chlorine by an amine, hydrogenolysis of the remaining chlorine, and nitrile hydrolysis.
- Harrington, Peter J.,Johnston, Dave,Moorlag, Henk,Wong, Jim-Wah,Hodges, L. Mark,Harris, Les,McEwen, Gerald K.,Smallwood, Blair
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p. 1157 - 1166
(2012/12/23)
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- 20-HYDROXYEICOSATETRAENOIC ACID PRODUCTION INHIBITORS
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A hydroxyformamidine compound represented by the following formula or a pharmaceutically acceptable salt thereof. [wherein R1 represents a substituted morpholino group, a substituted piperidino group, a piperazin-1-yl group, a substituted piperazin-1-yl group, a thiomorpholin-1-yl group, a perhydroazepin-1-yl group, a perhydroazocin-1-yl group, a tetrahydropyridin-1-yl group, a pyrrolin-1-yl group, etc.; X represents a nitrogen atom or a group represented by CR5; and R2 to R5 are the same or different and each represents a hydrogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a trifluoromethyl group or a halogen atom.] There is provided a drug which inhibi ts an enzyme producing 20-HETE participating in a contracting or dilating action for microvessels and an inducing action for cell proliferation in main organs such as kidney and cerebrovascular vessels.
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- Heteroaromatic substituted amides with antagonistic activity to neurokinin 1 receptors
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The present invention is a heteroaromatic substituted amide showing antagonist activity to neurokinin 1 (NK-1, substance P) receptors.
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- NK-1 receptor active amine oxide prodrugs
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Compounds of the invention are amine oxide prodrugs showing activity on the NK1 receptor.
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- Substituted 4-phenyl-pyridine compounds with activity as antagonists of neurokinin 1 receptors
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Substituted 4-phenyl-pyridine compounds with activity as antagonists of Neurokinin 1 receptors, methods of making these compounds and preparing.
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- Neuropeptide Y antagonists
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The compound is a neuropeptide Y antagonist and is effective in treating feeding disorders, cardiovascular diseases and other physiological disorders.
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Page column 34
(2010/02/05)
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- 2-(3,5-Bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide
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The invention relates to the compound of the formula which is 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolylpyridin-3-yl)-isobutyramide. It has been found that this compound has a high affinity to the NK-1 receptor and it is the
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- 4-phenyl-pyridine derivatives
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The compounds of the related invention are related to 4-phenyl-pyridine derivatives connected by a bridge containing oxygen or nitrogen to a phenyl derivative.
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- Nucleophilic substitutions at the pyridine ring: Kinetics of the reaction of 2-chloro-3-nitro and 2-chloro-5-nitropyridines with piperidine and morpholine in methanol and benzene
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The kinetics of the reactions of 2-chloro-3-nitropyridine (ortho-like) and 5-nitro (para-like) isomer with morpholine and piperidine were studied in methanol and benzene at several amine concentrations and temperatures in the range 25-45°C. The data show that k3-NO2/k5-NO2ratios are less than unity in methanol. The steric hindrance in the transition state of the 3-nitro (ortho-like) isomer retards o-substitution while the stability of p-quinonoid structure of the 5-nitro (para-like) isomer favors p-substitution. In benzene, the k3-NO2/k5-NO2 ratios are greater than unity. The hydrogen bonding formation between the ammonium hydrogen and the ortho-nitro group in the transition state of 3-nitro isomer favors the o-substitution.
- Hamed, Ezzat A.
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p. 599 - 605
(2007/10/03)
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- INVERSE ELECTRON DEMAND DIELS-ALDER REACTIONS OF 5-NITROPYRIMIDINE WITH ENAMINES. SYNTHESIS OF 3-NITROPYRIDINE DERIVATIVES
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The reaction of cyclic and non-cyclic enamines with 5-nitropyrimidine has been studied.Many enamines react in an inverse electron-demand Diels-Alder reaction, leading to the formation of 3-nitropyridines.N,S-ketene acetals were also found to react with 5-nitropyrimidines.The mechanism of the reaction will be discussed.
- Marcelis, Antonius T. M.,Plas, Henk C. van der
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p. 2693 - 2702
(2007/10/02)
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- Ring Transformations in Reactions of Heterocyclic Compounds with Nucleophiles. 1,3- and 1,4-Cycloadducts as Intermediates in the Pyrimidine to Pyridine Ring Transformation of 5-Nitropyrimidines by α-Phenylacetamidines
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5-Nitropyrimidine reacts with α-phenylacetamidines at -40 deg C to form ? adducts at the C-2 position of the ring but gives 2-aminopyridine derivatives at temperatures above 0 deg C.Experiments with 15N-labeled α-phenylacetamidine have shown th
- Charushin, Valery N.,Plas, Henk C. van der
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p. 2667 - 2671
(2007/10/02)
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- RING TRANSFORMATIONS OF 5-NITROPYRIMIDINE VIA INVERSE DIELS-ALDER REACTIONS
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5-Nitropyrimidine undergoes inverse Diels-Alder cycloadditions with ketene-N,N-, -O,O- acetals and enamines resulting in pyridine derivatives.The 1H NMR evidence for the 1-N,N-diethylaminopropyne cycloadduct formation is presented.
- Charushin, Valery N.,van der Plas, Henk C.
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p. 3965 - 3968
(2007/10/02)
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