103261-67-2Relevant articles and documents
Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors
Liu, Yongfu,Wu, Jun,Zhou, Mingwei,Chen, Wenming,Li, Dongbo,Wang, Zhanguo,Hornsperger, Benoit,Aebi, Johannes D.,M?rki, Hans-Peter,Kuhn, Bernd,Wang, Lisha,Kuglstatter, Andreas,Benz, J?rg,Müller, Stephan,Hochstrasser, Remo,Ottaviani, Giorgio,Xin, Jian,Kirchner, Stephan,Mohr, Susanne,Verry, Philippe,Riboulet, William,Shen, Hong C.,Mayweg, Alexander V.,Amrein, Kurt,Tan, Xuefei
, p. 6876 - 6897 (2020/08/14)
Aldosterone synthase (CYP11B2) inhibitors have been explored in recent years as an alternative therapeutic option to mineralocorticoid receptor (MR) antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including the heart, vasculature, kidney, and central nervous system (CNS). A benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones CYP11B2 inhibitors. Our systematic structure-activity relationship study enabled us to identify unique structural features that result in high selectivity against the closely homologous cortisol synthase (CYP11B1). We evaluated advanced lead molecules, exemplified by compound 52, in an in vivo cynomolgus monkey acute adrenocorticotropic hormone (ACTH) challenge model and demonstrated a superior 100-fold in vivo selectivity against CYP11B1.
Method for preparing 2-methyl-4-formaldoxime methyl benzoate
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Paragraph 0015; 0016, (2017/04/03)
The invention discloses a method for preparing 2-methyl-4-formaldoxime methyl benzoate. The method comprises the following steps: performing acylating chlorination on 2-methyl-4-bromobenzoic acid, carrying out methanol esterification and cyano substitution, and then performing nucleophilic addition elimination with hydroxylamine hydrochloride under alkaline conditions to obtain a target product. The method has the advantages that the process route is simple; reaction conditions are mild; the product yield is high; the total yield reaches 61 percent; the product quality is high; the appearance is white solid; the purity reaches 99.2 percent.
BICYCLOHETEROARYL-HETEROARYL-BENZOIC ACID COMPOUNDS AS RETINOIC ACID RECEPTOR BETA (RARβ) AGONISTS
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Page/Page column 69; 70, (2016/07/05)
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain bicycloheteroaryl-heteroaryl-benzoic acid compounds of the following formula (for convenience, collectively referred to herein as "BHBA compou
Development of Bifunctional Inhibitors of Polo-Like Kinase 1 with Low-Nanomolar Activities Against the Polo-Box Domain
Scharow, Andrej,Knappe, Daniel,Reindl, Wolfgang,Hoffmann, Ralf,Berg, Thorsten
, p. 759 - 767 (2016/04/26)
Polo-like kinase 1 (Plk1), a validated cancer target, harbors a protein-protein interaction domain referred to as the polo-box domain (PBD), in addition to its enzymatic domain. Although functional inhibition either of the enzymatic domain or of the PBD has been shown to inhibit Plk1, so far there have been no reports of bifunctional agents with the potential to target both protein domains. Here we report the development of Plk1 inhibitors that incorporate both an ATP-competitive ligand of the enzymatic domain, derived from BI 2536, and a functional inhibitor of the PBD, based either on the small molecule poloxin-2 or on a PBD-binding peptide. Although these bifunctional agents do not seem to bind both protein domains simultaneously, the most potent compound displays low-nanomolar activity against the Plk1 PBD, with excellent selectivity over the PBDs of Plk2 and Plk3. Our data provide insights into challenges and opportunities relating to the optimization of Plk1 PBD ligands as potent Plk1 inhibitors.
Novel Imidazoles for the Treatment and Prophylaxis of Respiratory Syncytial Virus Infection
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, (2016/11/28)
The invention provides novel compounds having the general formula: wherein R1, R2, R3 and Q are as described herein, compositions including the compounds and methods of using the compounds.
SPIRODIAMINE DERIVATIVES AS ALDOSTERONE SYNTHASE INHIBITORS
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Page/Page column 41, (2016/05/02)
The invention provides compounds having the general formula (I) pharmaceutical compositions containing the compounds and a process for their preparation. The compounds act as aldosterone synthase inhibitors and are for use in the treatment or prevention of chronic kidney disease, congestive heart failure, hypertension, primary aldosteronism and Cushing syndrom.
IMIDAZOLES FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS INFECTION
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, (2015/08/06)
The invention provides novel compounds having the general formula: (I) wherein R1, R2, R3 and Q are as described herein, compositions including the compounds and methods of using the compounds.
Modulators of methyl modifying enzymes, compositions and uses thereof
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, (2015/12/26)
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
NEW 3,4-DIHYDRO-2H-ISOQUINOLINE-1-ONE AND 2,3-DIHYDRO-ISOINDOL-1-ONE COMPOUNDS
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, (2014/12/12)
The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, A, m, n and p are as described herein, compositions including the compounds and methods of using the compounds.
NEW 3,4-DIHYDRO-2H-ISOQUINOLINE-1-ONE AND 2,3-DIHYDRO-ISOINDOL-1-ONE COMPOUNDS
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, (2014/12/12)
The invention provides novel compounds having the general formula (I) (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, A, m, n and p described herein, compositions including the compounds and methods of using the compounds.