- 3-OXAZOLINONE COMPOUND, PREPARATION METHOD THEREFOR AND PHARMACEUTICAL APPLICATION THEREOF
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The present invention relates to a novel 3-indazolinone compound that regulates or inhibits the activity of indoleamine 2,3-dioxygenase (IDO), the method for the preparation thereof and the use thereof in medicine. In particular, the present invention relates to a compound represented by the general formula (I) and a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, a method for treating or preventing IDO-mediated diseases, especially tumors, by use of the compound or a pharmaceutically acceptable salt thereof, and a method for preparing the compound or a pharmaceutically acceptable salt thereof. The present invention further relates to use of the compound or a pharmaceutically acceptable salt thereof or a composition comprising the compound or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating or preventing IDO-mediated diseases, especially tumors.Wherein the substituents of the general formula (I) are defined the same as that in the specification.
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Paragraph 0066; 0081-0082
(2021/04/16)
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- Intramolecular Pd-catalyzed reductive amination of enolizable sp3-C-H bonds
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A palladium-catalyzed reductive cyclization of nitroarenes has been designed to construct sp3-C-NHAr bonds from sp3-C-H bonds by using an enolizable nucleophile to intercept a nitrosoarene intermediate. Exposure of ortho-substituted nitroarenes to 5 mol ?% of Pd(OAc)2 and 10 mol ?% of phenanthroline under 2 atm of CO constructs partially saturated 5-, 6-, or 7-membered N-heterocycles using α-pyridyl carboxylates, malonates, 1,3-dimethylbarbituric acid, 1,3-diones, or difurans as the nucleophile.
- Ford, Russell L.,Alt, Isabel,Jana, Navendu,Driver, Tom G.
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supporting information
p. 8827 - 8831
(2019/10/28)
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- Structure-Based Drug Design of Potent Pyrazole Derivatives against Rhinovirus Replication
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Rhinoviruses (RVs) have been linked to exacerbations of many pulmonary diseases, thus increasing morbidity and/or mortality in subjects at risk. Unfortunately, the wide variety of RV genotypes constitutes a major hindrance for the development of Rhinovirus replication inhibitors. In the current investigation, we have developed a novel series of pyrazole derivatives that potently inhibit the Rhinovirus replication. Compounds 10e and 10h behave as early stage inhibitors of Rhinovirus infection with a broad-spectrum activity against RV-A and RV-B species (EC50 0.1 μM). We also evaluate the dynamics of the emerging resistance of these promising compounds and their in vitro genotoxicity. Molecular docking experiments shed light on the pharmacophoric elements interacting with residues of the drug-binding pocket.
- Da Costa, Laurène,Scheers, Els,Coluccia, Antonio,Casulli, Adriano,Roche, Manon,Di Giorgio, Carole,Neyts, Johan,Terme, Thierry,Cirilli, Roberto,La Regina, Giuseppe,Silvestri, Romano,Mirabelli, Carmen,Vanelle, Patrice
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p. 8402 - 8416
(2018/09/18)
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- Rh2(II)-catalyzed selective aminomethylene migration from styryl azides
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Rh2(II)-Carboxylate complexes were discovered to promote the selective migration of aminomethylenes in β,β-disubstituted styryl azides to form 2,3-disubstituted indoles. Mechanistic data are also presented that suggest that the migration occurs stepwise before diffusion of the iminium ion.
- Kong, Chen,Jana, Navendu,Driver, Tom G.
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supporting information
p. 824 - 827
(2013/03/29)
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- Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(2′,4′,6′-trimethoxystyrylsulfonyl)methyl] phenylamino}acetate (ON 01910.Na): Synthesis, structure-activity relationship, and biological activity
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Cyclin D proteins are elevated in many cancer cells, and targeted deletion of cyclin D1 gene in the mammary tissues protects mice from breast cancer. Accordingly, there is an increasing awareness of this novel nonenzymatic target for cancer therapeutics. We have developed novel, nonalkylating styrylbenzylsulfones that induce cell death in wide variety of cancer cells without affecting the proliferation and survival of normal cells. The development of derivatized styrylbenzylsulfones followed logically from a tumor cell cytotoxicity screen performed in our laboratory that did not have an a priori target profile. Modifications of some of the precursor molecules led to lead optimization with regard to tumor cell cytotoxicity. In this report we describe the synthesis and structure-activity relationships of novel, nonalkylating (E)-styrylbenzylsulfones and the development of the novel anticancer agent sodium (E)-2-{2-methoxy-5-[(2′,4′,6′- trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na), which is in phase III trials for myelodysplastic syndromes (MDS) associated with aberrant expression of cyclin D proteins.
- Reddy, M. V. Ramana,Venkatapuram, Padmavathi,Mallireddigari, Muralidhar R.,Pallela, Venkat R.,Cosenza, Stephen C.,Robell, Kimberly A.,Akula, Balaiah,Hoffman, Benjamin S.,Reddy, E. Premkumar
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experimental part
p. 6254 - 6276
(2011/11/01)
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- AMINO SUBSTITUTED DIARYL [A, D] CYCLOHEPTENE ANALOGS AS MUSCARINIC AGONISTS AND METHODS OF TREATMENT OF NEUROPSYCHIATRIC DISORDERS
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Disclosed herein are analogs of clozapine and pharmaceutically acceptable salts, esters, amides, or prodrugs thereof; methods of synthesizing the analogs; and methods of using the analogs for treating neuorpsychiatric disorders. In some embodiments, the analogs are amino substituted diaryl[a,d]cycloheptenes.
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Page/Page column 39, 40
(2011/04/14)
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- Isotope effects in photochemistry: Application to chromatic orthogonality
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Equation Presented The main challenge in developing new wavelength-specific photolabile protecting groups is the rigorous control of the photolysis rate. This rate is controlled by two factors: the chromophore absorbance and the reaction quantum yield. Fine-tuning the properties by changing substituents or structural features is difficult, because both factors are independently affected. By the use of the kinetic isotope effect, we could tune the quantum yield without altering the absorbance, and hence control the overall reaction rate. We exemplified this approach with chromatically orthogonally protected diesters.
- Blanc, Aurelien,Bochet, Christian G.
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p. 2649 - 2651
(2008/02/08)
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- Novel 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists with improved cellular activity
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The disruption of the p53-Hdm2 protein-protein interaction induces cell growth arrest and apoptosis. We have identified the 1,4-benzodiazepine-2,5-dione scaffold as a suitable template for inhibiting this interaction by binding to the Hdm2 protein. Several compounds have been made with improved potency, solubility, and cell-based activities.
- Leonard, Kristi,Marugan, Juan Jose,Raboisson, Pierre,Calvo, Raul,Gushue, Joan M.,Koblish, Holly K.,Lattanze, Jennifer,Zhao, Shuyuan,Cummings, Maxwell D.,Player, Mark R.,Maroney, Anna C.,Lu, Tianbao
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p. 3463 - 3468
(2007/10/03)
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- FIBROSIS INHIBITOR
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Medicament being useful as a fibrosis inhibitor for organs or tissues, which comprises a compound of the formula (I): wherein Ring Z is optionally substituted pyrrole ring, etc.; W2 is -CO-, -SO2-, optionally substituted C1-C4 alkylene, etc.; Ar2 is optionally substituted aryl, etc.; W1 and Ar1 mean the following (1) and (2):(1) W1 is optionally substituted C1-C4 alkylene, etc.; Ar1 is optionally substituted bicyclic heteroaryl having 1 to 4 nitrogen atoms as ring-forming atoms:(2) W1 is optionally substituted C2-C5 alkylene, optionally substituted C2-C5 alkenylene, etc.; and Ar1 is aryl or monocyclic heteroaryl, which is substituted by carboxyl, alkoxycarbonyl, etc. at the ortho- or meta-position thereof with respect to the binding position of W1, or a pharmaceutically acceptable salt thereof.
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- Pyrrole derivatives
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Pyrrole derivatives represented by the following formula: wherein Ring Z is an optionally substituted pyrrole ring, etc.; W2 is —CO—, —SO2—, an optionally substituted C1-C4 alkylene, etc.; Ar2 is an optionally substituted aryl, etc.; W2 and Ar1 mean the following (1) and (2): (1) W1 is an optionally substituted C1-C4 alkylene, etc.; Ar1 is an optionally substituted bicyclic heteroaryl having 1 to 4 nitrogen atoms as ring-forming atoms: (2) W1 is an optionally substituted C2-C5 alkylene, an optionally substituted C2-C5 alkenylene, etc.; and Ar1 is an aryl or monocyclic heteroaryl, which are substituted by carboxyl, an alkoxycarbonyl, etc. at the ortho- or meta-position thereof with respect to the binding position of W1, or a pharmaceutically acceptable salt thereof These compounds are useful as medicaments such as a fibrosis inhibitor for organs or tissues.
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- A Simple Economical Procedure for Selective Reduction of Aldehydes in Presence of Ketones
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A simple, efficient, and economical method for chemoselective reduction of aldehydes in the presence of ketones using stoichiometric amounts of sodium borohydride under phase-transfer catalysis is described.Aliphatic, aromatic and unsaturated aldehydes are reduced rapidly in high yields while dialkyl, aralkyl, diaryl and cycloaliphatic ketones are practically inert under the same conditions.Some exceptions are noted.The scope of the present method is illustrated with suitable examples of selective and competitive reductions.The high reactivity of the phase-transferred borohydride species as compared to that of pre-formed quaternary ammonium borohydrides is noted.
- Rao, C. Someswara,Deshmukh, A. A.,Patel, B. J.
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p. 626 - 629
(2007/10/02)
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