181585-93-3Relevant articles and documents
Annular tautomerism of 3(5)-disubstituted-1H-pyrazoles with ester and amide groups
Kusakiewicz-Dawid, Anna,Porada, Monika,Dziuk, B?azej,Siod?ak, Dawid
, (2019)
A series of disubstituted 1H-pyrazoles with methyl (1), amino (2), and nitro (3) groups, as well as ester (a) or amide (b) groups in positions 3 and 5 was synthesized, and annular tautomerism was investigated using X-ray, theoretical calculations, NMR, and FT-IR methods. The X-ray experiment in the crystal state showed for the compounds with methyl (1a, 1b) and amino (2b) groups the tautomer with ester or amide groups at position 3 (tautomer 3), but for those with a nitro group (3b, 4), tautomer 5. Similar results were obtained in solution by NMR NOE experiments in CDCl3, DMSO-d6, and CD3OD solvents. However, tautomer equilibrium was observed for 2b in DMSO. The FT-IR spectra in chloroform and acetonitrile showed equilibria, which can be ascribed to conformational changes of the cis/trans arrangement of the ester/amide group and pyrazole ring. Theoretical analysis using the M06-2X/6-311++G(d,p) method (in vacuo, chloroform, acetonitrile, and water) and measurement of aromaticity (NICS) showed dependence on internal hydrogen bonds, the influence of the environment, and the effect of the substituent. These factors, pyrazole aromaticity and intra- and inter-molecular interactions, seem to have a considerable influence on the choice of tautomer.
FUSED RING PYRIMIDONE DERIVATIVES FOR USE IN THE TREATMENT OF HBV INFECTION OR OF HBV-INDUCED DISEASES
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Page/Page column 100; 103; 125; 154; 279; 291, (2022/04/03)
Provided are compounds according to any of Formula (I-1) to (I-7), pharmaceutical compositions comprising at least one of said compounds, their use as a medicament, and their use in treating chronic hepatitis B virus (HBV) infection. Methods for preparing compounds according to any of Formula (I-1) to (I-7) are also provided.
Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3
Brawn, Ryan A.,Cook, Andrew,Omoto, Kiyoyuki,Ke, Jiyuan,Karr, Craig,Colombo, Federico,Virrankoski, Milena,Prajapati, Sudeep,Reynolds, Dominic,Bolduc, David M.,Nguyen, Tuong-Vi,Gee, Patricia,Borrelli, Deanna,Caleb, Benjamin,Yao, Shihua,Irwin, Sean,Larsen, Nicholas A.,Selvaraj, Anand,Zhao, Xuesong,Ioannidis, Stephanos
supporting information, p. 93 - 98 (2020/12/21)
Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clinical trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR analysis and structure-based drug design led to analogues with improved potency and drug metabolism and pharmacokinetics properties.
SELECTIVE FOXO INHIBITORS FOR TREATMENT OF DIABETES AND OTHER DISORDERS RELATED TO IMPAIRED PANCREATIC FUNCTION
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Paragraph 0121-0122, (2020/10/18)
Various embodiments relate to a compound (represented by Formula I) or a pharmaceutically acceptable salt or tautomer thereof. The compound may selectively inhibit a Forkhead Box O1 (FOXO1) transcription factor. Various embodiments relate to methods compr
APELIN RECEPTOR AGONISTS AND METHODS OF USE THEREOF
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Paragraph 0563-0565, (2019/02/25)
Provided herein are agonists of the apelin receptor for the treatment of disease. The compounds disclosed herein are useful for the treatment of a range of cardiovascular, renal and metabolic conditions.
HETEROCYCLIC COMPOUNDS AS PRMT5 INHIBITORS
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Paragraph 000213, (2019/06/11)
The compounds of Formula I, Formula Ia, and Formula Ib are described herein along with their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds inhibit PRMT5 and are useful as therpeautic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer's disease, Parkinson's disease and the like.
CHEMICAL COMPOUNDS AS INHIBITORS OF INTERLEUKIN-1 ACTIVITY
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Paragraph 001030; 001031; 001032, (2018/08/12)
The present disclosure relates to novel sulfonylurea and sulfonyl thiourea compounds and related compounds and their use in treating a disease or condition responsive to modulation of cytokines such as IL-1β and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process.
HETEROAROMATIC DERIVATIVES AS NIK INHIBITORS
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Page/Page column 317; 318, (2018/02/03)
The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.
PHOSPHONATE COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Paragraph 0461; 0580, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula (I), or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is a phosphonate substituent (R32) are provided. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.
ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Paragraph 0727, (2017/03/14)
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.
