- PROGRANULIN MODULATORS AND METHODS OF USING THE SAME
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Provided herein are compounds of formula (I) that modulate progranulin and methods of using the compounds in progranulin- associated disorders, such as Frontotemperal lobe dementia (FTLD).
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Paragraph 0400
(2021/04/30)
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- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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The present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, solid forms, combinations of pharmacologically active agents, pharmaceutical compositions and methods of using such compounds and solid forms thereof to treat or prevent parasitic diseases, for example malaria.
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Paragraph 0315; 0327-0328; 0474; 0488-0489
(2021/04/23)
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- Opioid receptor agonists and application thereof
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The invention discloses compounds and salts thereof that can be used as opioid receptor ligands, a preparation method of the compounds, compositions containing the compounds, and a use of the compounds as [mu] opioid receptor agonists; the compounds are used for treatment of [mu] opioid receptor-mediated related diseases, such as pains and pain-related disorders.
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Paragraph 1683; 1686-1691
(2019/01/24)
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- 1,9-DIAZASPIRO UNDECANE COMPOUNDS HAVING MULTIMODAL ACTIVITY AGAINST PAIN
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The present invention relates to compounds having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opiod receptor and more particularly to 1,9-diazaspiro undecane compounds having this pharmacological activity, to processes of
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Page/Page column 133-134
(2016/06/21)
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- Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19
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The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 (CCT251921), a potent, selective, and orally bioavailable inhibitor of CDK8 with equipotent affinity for CDK19. We describe a structure-based design approach leading to the discovery of a 3,4,5-trisubstituted-2-aminopyridine series and present the application of physicochemical property analyses to successfully reduce in vivo metabolic clearance, minimize transporter-mediated biliary elimination while maintaining acceptable aqueous solubility. Compound 109 affords the optimal compromise of in vitro biochemical, pharmacokinetic, and physicochemical properties and is suitable for progression to animal models of cancer.
- Mallinger, Aurélie,Schiemann, Kai,Rink, Christian,Stieber, Frank,Calderini, Michel,Crumpler, Simon,Stubbs, Mark,Adeniji-Popoola, Olajumoke,Poeschke, Oliver,Busch, Michael,Czodrowski, Paul,Musil, Djordje,Schwarz, Daniel,Ortiz-Ruiz, Maria-Jesus,Schneider, Richard,Thai, Ching,Valenti, Melanie,De Haven Brandon, Alexis,Burke, Rosemary,Workman, Paul,Dale, Trevor,Wienke, Dirk,Clarke, Paul A.,Esdar, Christina,Raynaud, Florence I.,Eccles, Suzanne A.,Rohdich, Felix,Blagg, Julian
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supporting information
p. 1078 - 1101
(2016/02/23)
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- SUBSTITUTED PYRIDINYL-PYRIMIDINES AND THEIR USE AS MEDICAMENTS
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The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R1, R2, R4, R3, R5 and R6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.
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Paragraph 0266-0268
(2013/03/26)
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- SUBSTITUTED PYRIDINYL-PYRIMIDINES AND THEIR USE AS MEDICAMENTS
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The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R1, R2, R4, R3, R5 and R6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.
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Page/Page column 97
(2012/08/08)
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- Microwave-assisted synthesis of cycloalkanespirohydantoins and piperidinespirohydantoins as precursors of restricted α-amino acids
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Cycloalkanespirohydantoins 3 and piperidinespirohydantoins 4 were synthesized from cycloalkanones 9 and piperidones 10 under microwave-assisted conditions. Results are compared with those obtained under thermal conditions. Cycloalkanespirohydantoins 3 were N-protected with Boc group and hydrolyzed under basic conditions to obtain five, six and seven-membered ring restricted α-amino acids 12 in very good overall yields (76-94%). ARKAT USA, Inc.
- Rivero, Ignacio A.,Reynoso-Soto, Edgar A.,Ochoa-Teran, Adrian
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experimental part
p. 260 - 271
(2011/05/13)
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- Hydantoin compounds
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The invention relates to the use of hydantoin compounds useful for treating or preventing autoimmune disorders. The present invention also provides compositions and uses thereof.
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Page/Page column 12
(2010/11/24)
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- Design, synthesis, and SAR of tachykinin antagonists: Modulation of balance in NK1/NK2 receptor antagonist activity
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Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.
- Albert, Jeffrey S.,Andisik, Donald,Barthlow, Herbert,Bernstein, Peter R.,Bialecki, Russell A.,Dedinas, Robert,Dembofsky, Bruce T.,Hill, Daniel,Kirkland, Karin,Koether, Gerard M.,Kosmider, Benedict J.,Ohnmacht, Cyrus,Palmer, William,Potts, William,Rumsey, William,Shen, Lihong,Shenvi, Ashok,Sherwood, Scott,Aharony, David,Warwick, Paul J.,Russell, Keith
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p. 3972 - 3983
(2007/10/03)
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- Substituted heterocycles
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Compounds of formula I STR1 wherein Q1, Q2, Q3, Q4 and Q5 have any of the meanings given in the specification, their N-oxides, and their pharmacuetically acceptable salts are nonpeptide antagonists NKA, useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.
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