- QUINAZOLINE COMPOUNDS, PREPARATION METHODS AND USES THEREOF
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Provided herein are novel compounds, for example, compounds having a Formula (I), Formula (II), or Formula (III), or a pharmaceutically acceptable salt thereof. Also provided herein are methods of preparing the compounds and methods of using the compounds, for example, in inhibiting KRAS G12D in a cancer cell, and/or in treating various cancer such as pancreatic cancer, colorectal cancer, lung cancer or endometrial cancer.
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Paragraph 230
(2022/01/12)
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- Formation of 6-Azaindoles by Intramolecular Diels-Alder Reaction of Oxazoles and Total Synthesis of Marinoquinoline A
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A new variant of the intramolecular Diels-Alder oxazole (IMDAO) cycloaddition that provides direct access to 6-azaindoles was developed. The IMDAO reaction was applied in a total synthesis of the aminophenylpyrrole-derived alkaloid marinoquinoline A, also
- Jhaveri, Dishit P.,Osano, Mana,Wipf, Peter
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supporting information
p. 2215 - 2219
(2020/04/09)
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- HETEROCYCLIC COMPOUNDS AND THEIR USE FOR TREATMENT OF HELMINTHIC INFECTIONS AND DISEASES
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Provided herein are Heterocyclic compounds of formula (I): and pharmaceutically acceptable salts, tautomers, isotopologues, or stereoisomers thereof, wherein W, X, Y, R1, R2, and RN are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound, and methods for treating or preventing animal and human filarial worm infections and diseases.
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Paragraph 00431
(2020/11/03)
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- Design, synthesis and biological evaluation of 7-chloro-9h-pyrimido[4,5-b]indole-based glycogen synthase kinase-3β inhibitors
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Glycogen synthase kinase-3β (GSK-3β) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer’s disease. We herein report on the optimization of a novel class of GSK-3β inhibitors based on the tofacitinib-derived screen hit 3-((3R,4R)-3-((7-chloro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino)-4-methylpiperidin-1-yl)-3-oxopropanenitrile (1). We synthesized a series of 19 novel 7-chloro-9H-pyrimido[4,5-b]indole-based derivatives and studied their structure–activity relationships with focus on the cyanoacetyl piperidine moiety. We unveiled the crucial role of the nitrile group and its importance for the activity of this compound series. A successful rigidization approach afforded 3-(3aRS,7aSR)-(1-(7-chloro-9H-pyrimido[4,5-b]indol-4-yl)octahydro-6H-pyrrolo[2,3-c]pyridin-6-yl)-propanenitrile (24), which displayed an IC50 value of 130 nM on GSK-3β and was further characterized by its metabolic stability. Finally, we disclosed the putative binding modes of the most potent inhibitors within the ATP binding site of GSK-3β by 1 μs molecular dynamics simulations.
- Andreev, Stanislav,Pantsar, Tatu,Ansideri, Francesco,Kudolo, Mark,Forster, Michael,Schollmeyer, Dieter,Laufer, Stefan A.,Koch, Pierre
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- PYRROLO[2,3-B]PYRIDINE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER
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The present application relates to a compound of Formula I, or a salt, hydrate or solvate thereof, as defined herein. The present compounds are found to have pharmacological effects, particularly at MRCK. Further provided are pharmaceutical compositions comprising said compounds. The present invention also relates to the use of these compounds as therapeutic agents, in particular, for the treatment and/or prevention of proliferative diseases, such as cancer.
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Paragraph 00153; 00206
(2019/03/05)
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- DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A BICYCLO MOIETY
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The disclosure provides compounds having formula (I), wherein the substituents are as defined herein. The compounds are useful for modulating the dopamine D3 receptor and for treating conditions associated therewith, such as addictions, drug dependency, and psychiatric conditions.
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Paragraph 1190; 1191
(2017/02/28)
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- ALANINE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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The description relates to inhibitors of Apoptosis Proteins (TAPs) binding compounds, including Afunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the IAP E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.
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Paragraph 00382
(2017/02/09)
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- ISOQUINOLINESULFONYL DERIVATIVE AS RHO KINASE INHIBITOR
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The present invention discloses a class of isoquinolinesulfonyl derivatives as RHO kinase inhibitors, and pharmaceutical compositions thereof, and relates to pharmaceutically acceptable uses thereof. Specifically, the present invention relates to a compound as represented by formula (I), or a pharmaceutically acceptable salt thereof.
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Paragraph 0147; 0148
(2017/06/12)
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- 6,5-BICYCLIC OCTAHYDROPYRROLOPYRIDINE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to 6,5-bicyclic octahydropyrrolopyridine compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 56
(2016/07/05)
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- PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYR-ROLO[2,3-D]PYRIDINYL ACRYLAMIDES
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The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.
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Paragraph 0306
(2015/06/17)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 0403-0404
(2014/08/19)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter-and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 00268
(2013/06/05)
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- HETEROCYCLIC TYROSINE KINASE INHIBITORS
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The present invention provides compounds useful as inhibitors of Tec family kinases, compositions thereof, and methods of using the same. In certain embodiments, the present invention provides pharmaceutical formulations comprising provided compounds. In certain embodiments, the present invention provides a method of decreasing enzymatic activity of a Tec kinase family member. In some embodiments, such methods include contacting a Tec kinase family member with an effective amount of a Tec kinase family member inhibitor. In certain embodiments, the present invention provides a method of treating a disorder responsive to Tec kinase family inhibition in a subject in need thereof.
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Page/Page column 181
(2012/05/19)
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- PYRROLOPYRIDINES AS KINASE INHIBITORS
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Compounds of Formula (I) are useful for inhibition of CHKl and/or CHK2. Methods of using compounds of Formula (I) and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
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Page/Page column 108
(2009/12/23)
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- PYRIDINE AND PYRAZINE DERIVATIVES AS MNK KINASE INHIBITORS
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The present invention relates to compounds of the general formula (I) wherein X, Y, Z, A, Ar, R1, R2, R3, and R4 are as defined herein, which compounds are inhibitors of MNK2 and MNK1. The invention also relates to the use of the compounds in therapy, pharmaceutical compositions comprising the compounds, and the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of disorders related to undesired activity of MNK1 and/or MNK2 kinases.
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Page/Page column 162-163
(2008/06/13)
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- Heterobicyclic pyrazole compounds and methods of use
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Compounds of Formulas Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
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Page/Page column 115
(2008/06/13)
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- Diazabicyclic central nervous system active agents
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Compounds of formula I pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.
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