- Di-bromo-Based Small-Molecule Inhibitors of the PD-1/PD-L1 Immune Checkpoint
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Immune checkpoint blockade is one of the most promising strategies of cancer immunotherapy. However, unlike classical targeted therapies, it is currently solely based on expensive monoclonal antibodies, which often inflict immune-related adverse events. H
- Konieczny, Magdalena,Musielak, Bogdan,Kocik, Justyna,Skalniak, Lukasz,Sala, Dominik,Czub, Miroslawa,Magiera-Mularz, Katarzyna,Rodriguez, Ismael,Myrcha, Maja,Stec, Malgorzata,Siedlar, Maciej,Holak, Tad A.,Plewka, Jacek
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supporting information
p. 11271 - 11285
(2020/11/09)
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- PROBES FOR IMAGING HUNTINGTIN PROTEIN
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Provided are imaging agents comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and methods of their use.
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- HETEROCYCLIC COMPOUND AND H1 RECEPTOR ANTAGONIST
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A heterocyclic compound useful as an antiallergic agent is provided. A compound represented by the following formula (1) or a salt thereof: wherein the ring A is a homocyclic or heterocyclic ring; the ring B is a heterocyclic ring which contains G and nitrogen atom N as constituent atoms thereof, wherein G is CH or N; R1 is a carbonyl group or an alkylene group; R2a and R2b are an alkyl group, a cycloalkyl group, an aryl group, or a heterocyclic group; X is an oxygen atom or a sulfur atom; Z is a hydroxyl group, an alkoxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy group, an amino group, or an N-substituted amino group; and n is 0 or 1; with the proviso that when the ring A is a benzene ring or when the ring B is a piperazine ring, R1 is an alkylene group which may have a substituent.
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- A new photolabile protecting group for release of carboxylic acids by visible-light-induced direct and mediated electron transfer
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(Chemical Equation Presented) A new aqueous-compatible photoinduced electron transfer based photolabile protecting group has been developed for the release of carboxylic acids. The reduction potential of this group is more positive than previous systems,
- Borak, J. Brian,Falvey, Daniel E.
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supporting information; experimental part
p. 3894 - 3899
(2009/10/02)
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- NOVEL COMPOUND HAVING 4-PYRIDYLALKYLTHIO GROUP AS SUBSTITUENT
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A subject of the present invention is to provide a novel aromatic five- or six-memberd heterocyclic derivative having 4-pyridylalkylthio as a substituent or a salt thereof which is useful as a pharmaceutical. Compound represented by the following general formula [I] or salts thereof are useful as therapeutic agents for diseases in which angiogenesis or augmentation of vascular permeability is involved. In the formula, ring "A" is a benzene ring or an aromatic five- or six-memberd heterocycle which can be fused with a cycloalkane ring, "B" is alkylene, R1 and R2, the same or different, are H, OH, substituted or unsubstituted alkoxy and the like, X and Y, the same or different, are group(s) selected from H, halogen, OH, substituted or unsubstituted alkoxy and the like respectively, p is 0, 1 or 2, and q is 0 or 1.
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Page/Page column 52-53
(2008/06/13)
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- NOVEL INDOLE DERIVATES AS FABP-4 INHIBITORS
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The present invention relates to novel compounds (I) wherein R0, R1, R2, R3, R4, R5, R6, R7, R8, A, B, n, X, and Y are as defined in the description and claims; and also to pharmaceutical compositions comprising the compounds, as well as to the use of the compounds in medicine and for the preparation of a medicament, which acts on the fatty acid binding protein FABP-4. The present invention relates to novel compounds (I) wherein R0, R1, R2, R3, R4, R5, R6, R7, R8, A, B, n, X, and Y are as defined in the description and claims; and also to pharmaceutical compositions comprising the compounds, as well as to the use of the compounds in medicine and for the preparation of a medicament, which acts on the fatty acid binding protein FABP-4.
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- Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src
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Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. We report here the discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Special attention was directed toward finding inhibitors selective against KDR tyrosine kinase in order to ensure that the in vivo profile of a specific Src inhibitor could be determined. The 4-aminobenzodioxole quinazoline series gave compounds with excellent potency and selectivity. The most interesting compounds were evaluated in vivo and displayed good pharmacokinetics following oral dosing. Compounds such as the aminobenzodioxoles were shown to be potent inhibitors of tumor growth in a c-Src-transformed 3T3 xenograft model in vivo, resulting in more than 90% growth inhibition at doses as low as 6 mg/kg po once daily. Src tyrosine kinase inhibitors such as these may provide a novel therapeutic modality for targeting cancer invasion and metastasis.
- Plé, Patrick A.,Green, Tim P.,Hennequin, Laurent F.,Curwen, Jon,Fennell, Michael,Allen, Jack,Lambert-Van Der Brempt, Christine,Costello, Gerard
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p. 871 - 887
(2007/10/03)
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- Chemical compounds
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The invention relates to quinazoline derivatives of the formula: [wherein: Y1represents —O—, —S—, —CH2—, —SO—, —SO2—, —NR5CO—, —CONR6—, —SO2NR7—, —NR8SO2— or —NR9— (wherein R5, R6, R8and R9each independently represents hydrogen, alkyl or alkoxyalkyl); R1represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, alkyl, alkoxy, alkylthio, amino or alkylamino. R2represents hydrogen, hydroxy, halogeno, alkyl, alkoxy, trifluoromethyl, cyano, amino or nitro; m is an integer from 1 to 5; R3represents hydroxy, halogeno, alkyl, alkoxy, alkanoyloxy, trifluoromethyl, cyano, amino or nitro; R4represents a group which is or which contains an optionally substituted pyridone, phenyl or aromatic heterocyclic group] and salts thereof; processes for their preparation and pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
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- Indole compounds as COX-2 inhibitors
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This invention provides a compound of the following formula: and the pharmaceutically acceptable salts thereof, wherein L is oxygen or sulfur; Y is a direct bond or C1-4alkylidene; Q is C1-6alkyl, C3-7cycloalkyl, phenyl, naphthyl, heteroaryl or the like; R1is hydrogen, C1-6alkyl or the like; R2is hydrogen, C1-4alkyl, C(O)R5wherein R5is C1-22alkyl or C2-22alkenyl, halosubstituted C1-8alkyl, halosubstituted C2-8alkenyl, —Y—C3-7cycloalkyl, —Y—C3-7cycloalkenyl, phenyl, naphthyl, heteroaryl or the like; X is halo, C1-4alkyl, hydroxy, C1-4alkoxy or the like; and n is 0, 1, 2 or 3, with the proviso that a group of formula —Y—Q is not methyl or ethyl when X is hydrogen; L is oxygen; R1is hydrogen; and R2is acetyl. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.
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- Substituted sulfonic acid N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds
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The compounds of formula I exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More specifically, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, which are for treating a patient suffering from, or subject to, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.
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- Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa
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The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(s)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (K1 = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.
- Ewing, William R.,Becker, Michael R.,Manetta, Vincent E.,Davis, Roderick S.,Pauls, Henry W.,Mason, Helen,Choi-Sledeski, Yong Mi,Green, Daniel,Cha, Don,Spada, Alfred P.,Cheney, Daniel L.,Mason, Jonathan S.,Maignan, Sebastien,Guilloteau, Jean-Pierre,Brown, Karen,Colussi, Dennis,Bentley, Ross,Bostwick, Jeff,Kasiewski, Charles J.,Morgan, Suzanne R.,Leadley, Robert J.,Dunwiddie, Christopher T.,Perrone, Mark H.,Chu, Valeria
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p. 3557 - 3571
(2007/10/03)
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