- PYRAZOLOPYRAZINES ACTING ON CANCERS VIA INHIBITION OF CDK12
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The present invention provides compounds of general formula (I) in which X, R1, R2 and R3 are as described and defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and/or prophylaxis of diseases, in particular of hyperproliferative disorders such as cancer disorders, as a sole agent or in combination with other active ingredients.
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- COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF
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The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.
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- COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF
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The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.
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- 5-(4-PYRIDYLOXY)PYRAZOLE COMPOUNDS SERVING AS TGF-BETA R1 KINASE INHIBITOR
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Disclosed are a group of 5-(4-pyridyloxy)pyrazole compounds serving as a TGF-βR1 kinase inhibitor, and applications of same in preparing a TGF-βR1 kinase inhibitor medicament. Specifically disclosed are the compounds as represented by formula (I), a pharm
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- Growth Factor Receptor antagonists. Preparation method and application thereof
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The invention relates to a small molecule antagonist for transforming growth factor β receptors, a method for preparing the small molecule antagonist, and application of the small molecule antagonist in preparation of drugs. The small molecule antagonist for transforming the growth factor β receptor has the application of treating and/or preventing various diseases mediated by ALK5, and has great clinical application potential.
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Paragraph 0107-0112
(2021/11/27)
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- Discovery, synthesis and characterization of a series of (1-alkyl-3-methyl-1H-pyrazol-5-yl)-2-(5-aryl-2H-tetrazol-2-yl)acetamides as novel GIRK1/2 potassium channel activators
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The present study describes the discovery and characterization of a series of 5-aryl-2H-tetrazol-3-ylacetamides as G protein-gated inwardly-rectifying potassium (GIRK) channels activators. Working from an initial hit discovered during a high-throughput screening campaign, we identified a tetrazole scaffold that shifts away from the previously reported urea-based scaffolds while remaining effective GIRK1/2 channel activators. In addition, we evaluated the compounds in Tier 1 DMPK assays and have identified a (3-methyl-1H-pyrazol-1-yl)tetrahydrothiophene-1,1-dioxide head group that imparts interesting and unexpected microsomal stability compared to previously-reported pyrazole head groups.
- Sharma, Swagat,Kozek, Krystian A.,Abney, Kristopher K.,Kumar, Sushil,Gautam, Nagsen,Alnouti, Yazen,David Weaver,Hopkins, Corey R.
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p. 791 - 796
(2019/02/06)
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- ANNULATED GLYCOSIDASE INHIBITORS
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Compounds of formula (I) wherein A, R, W1, W2, W3, W4, W5, W6, L, Q, Rx and u have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.
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Page/Page column 113; 114
(2019/03/12)
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- HYDRAZINE COMPOUND AS BLOOD COAGULATION FACTOR Xa INHIBITOR
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Provided is a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein X is selected from a 3-9 membered carbon ring or its phenyl ring, and a 4-10 membered heterocyclic ring or its benzo ring; Y and Z are independently selected from 4-9 membered saturated heterocyclic rings respectively; RI-3 are independently selected from H, F, Cl, Br, I, CN, OH, SH,NH2, CHO, COOH respectively, or selected from C1-10 alkyls or heteroalkyls optionally substituted by R01, C3-10 alkyls ring hydrocarbon groups or heterocyclic hydrocarbon groups, C1-10 alkyls or heteroalkyls substituted by C3-10 ring hydrocarbon groups or heterocyclic hydrocarbon group. The compound can be used as an anticoagulant for treating and preventing thrombotic disorders, and can meet the real needs of selectivity and a potent inhibitor for coagulation Xa.
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Paragraph 0110
(2017/04/11)
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- PYRAZOLOPYRIMIDINES AS INHIBITORS OF GLUCOCORTICOID RECEPTOR TRANSLOCATION
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Provided herein are compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of Glucocorticoid Receptor (GR) translocation. Furthermore, the subject compounds and compositions are useful for the treatment of diseases involved in the hypothalamic-pituitary-adrenal (HPA) axis.
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- HETEROCYCLIC COMPOUND
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The present invention provides a compound having a superior JAK inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases (rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus, etc.), cancer (leukemia, uterine leiomyosarcoma, prostate cancer, multiple myeloma, cachexia, myelofibrosis, etc.) and the like, or a salt thereof. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.
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Paragraph 0431
(2015/04/15)
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- PROTEIN KINASE INHIBITORS
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The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors of the members of the Tec and Src protein kinase families.
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- PROTEIN KINASE INHIBITORS
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The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors of the members of the Tec and Src protein kinase families.
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- AZAINDAZOLES
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Herein are disclosed azaindazoles of formula (I), (I), where the various groups are defined herein, and which are useful for treating cancer.
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Page/Page column 134
(2013/03/28)
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- Design and discovery of 6-[(3 s,4 s)-4-methyl-1-(pyrimidin-2-ylmethyl) pyrrolidin-3-yl]-1-(tetrahydro-2 h -pyran-4-yl)-1,5-dihydro-4 h -pyrazolo[3,4- d ]pyrimidin-4-one (PF-04447943), a selective brain penetrant pde9a inhibitor for the treatment of cognitive disorders
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6-[(3S,4S)-4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl] -1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943) is a novel PDE9A inhibitor identified using parallel synthetic chemistry and structure-based drug design (SBDD) and has advanced into clinical trials. Selectivity for PDE9A over other PDE family members was achieved by targeting key residue differences between the PDE9A and PDE1C catalytic site. The physicochemical properties of the series were optimized to provide excellent in vitro and in vivo pharmacokinetics properties in multiple species including humans. It has been reported to elevate central cGMP levels in the brain and CSF of rodents. In addition, it exhibits procognitive activity in several rodent models and synaptic stabilization in an amyloid precursor protein (APP) transgenic mouse model. Recent disclosures from clinical trials confirm that it is well tolerated in humans and elevates cGMP in cerebral spinal fluid of healthy volunteers, confirming that it is a quality pharmacological tool for testing clinical hypotheses in disease states associated with impairment of cGMP signaling or cognition.
- Verhoest, Patrick R.,Fonseca, Kari R.,Hou, Xinjun,Proulx-Lafrance, Caroline,Corman, Michael,Helal, Christopher J.,Claffey, Michelle M.,Tuttle, Jamison B.,Coffman, Karen J.,Liu, Shenpinq,Nelson, Frederick,Kleiman, Robin J.,Menniti, Frank S.,Schmidt, Christopher J.,Vanase-Frawley, Michelle,Liras, Spiros
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p. 9045 - 9054
(2013/01/15)
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- PI3K (DELTA) SELECTIVE INHIBITORS
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Novel PI3K, especially PI3K delta isoform, selective inhibitors are disclosed. The compounds are useful in treating disorders related to abnormal PI3K or PI3Kδ activities such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders.
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- PYRAZOLE OXADIAZOLE DERIVATIVES AS S1P1 AGONISTS
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The present invention relates to pyrazole oxadiazoles derivatives of Formula (I), and their use for treating multiple sclerosis and other diseases. Wherein R1, R2 and R3 are as defined in the description.
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Page/Page column 80-81
(2010/12/29)
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- PI3K/MTOR KINASE INHIBITORS
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6-morpholin-4-yl-pyrazolo[3,4-d]pyrimidine and 2-morpholin-4-yl-7H- pyrrolo[2,3-d]pyrimidine derivatives have unexpected drug properties as inhibitors of PI3 and/or mTOR kinases and are useful in treating disorders related to abnormal PI3K/mT0R activities such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders.
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Page/Page column 54
(2010/06/15)
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- AMINO-HETEROCYCLIC COMPOUNDS
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The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R, R1, R2 and R3 are as defined herein. Pharmaceutical compositions containing the compounds of Formul
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Page/Page column 35-36
(2009/02/11)
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- 1-HETEROCYCLYL-1,5-DIHYDRO-PYRAZOLO[3,4-D] PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A MODULATORS
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The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, Formula (I) with Hc is a mono-, bi- or tricyclic heterocyclyl group, the ring members of which are carbon atoms and at least 1, preferably 1, 2 or 3, heteroatom(s), which are selected from the group of nitrogen, oxygen and sulphur, which is in the form of -S(O)r - with r being 0, 1 or 2, and - said heterocyclyl group is or comprises 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member and - said heterocyclyl group is bound to the scaffold by said 1 non- aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease.
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Page/Page column 172-173
(2009/10/30)
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- THIAZOLYL-DIHYDRO-INDAZOLES
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The present invention encompasses compounds of general formula (1) wherein R1 to R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a
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Page/Page column 53; 54
(2009/10/22)
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- AMINO-HETEROCYCLIC COMPOUNDS
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The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R, R1, R2 and R3 are as defined herein. Pharmaceutical compositions containing the compounds of Formul
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Page/Page column 90; 46
(2009/01/20)
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- Hydrazinopyrimidines as cysteine protease inhibitors
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Substituted heteroaryl nitrile derivatives of Formula I, processes for their preparation, pharmaceutical compositions comprising such compounds and use of the compounds as cysteine protease inhibitors are provided.
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Page/Page column 27-28
(2008/12/04)
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- Discovery and characterization of novel, potent, non-peptide parathyroid hormone-1 receptor antagonists
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A 1,3,4-benzotriazepine was identified as a suitable lead in our effort toward obtaining a non-peptide parathyroid hormone-1 receptor (PTH1R) antagonist. A process of optimization afforded derivatives displaying nanomolar PTH1R affinity, a representative example of which behaved as a PTH1R antagonist in cell-based cyclic adenosine monophosphate (cAMP) assays, with selectivity over PTH2 receptors.
- McDonald, Iain M.,Austin, Carol,Buck, Ildiko M.,Dunstone, David J.,Gaffen, John,Griffin, Eric,Harper, Elaine A.,Hull, Robert A. D.,Kalindjian, S. Barret,Linney, Ian D.,Low, Caroline M. R.,Patel, Dipa,Pether, Michael J.,Raynor, Michelle,Roberts, Sonia P.,Shaxted, Mark E.,Spencer, John,Steel, Katherine I. M.,Sykes, David A.,Wright, Paul T.,Xun, Wei
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p. 4789 - 4792
(2008/03/13)
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- BENZOTRIAZEPINONE DERIVATIVES
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The present invention is concerned with benzotriazepinone derivatives, their intermediates, uses thereof and processes for their production. In particular, the present invention relates to parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrp) receptor ligands, (PTH-1 or PTH/PTHrp receptor ligands). The invention also relates to methods of preparing such ligands and to compounds which are useful as intermediates in such methods.
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Page/Page column 62
(2010/11/29)
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- BENZOTRIAZEPINONE DERIVATIVES
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The present invention is concerned with benzotriazepinone derivatives, their intermediates, uses thereof and processes for their production. In particular, the present invention relates to parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrp) receptor ligands, (PTH-I or PTH/PTHrp receptor ligands). The invention also relates to methods of preparing such ligands and to compounds which are useful as intermediates in such methods.
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Page/Page column 56
(2010/11/29)
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- Synthesis and Selective Cyclooxygenase-2 Inhibitory Activity of a Series of Novel, Nitric Oxide Donor-Containing Pyrazoles
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The synthesis of a series of novel pyrazoles containing a nitrate (ONO 2) moiety as a nitric oxide (NO)-donor functionality is reported. Their COX-1 and COX-2 inhibitory activities in human whole blood are profiled. Our data demonstrate that py
- Ranatunge, Ramani R.,Augustyniak, Michael,Bandarage, Upul K.,Earl, Richard A.,Ellis, James L.,Garvey, David S.,Janero, David R.,Letts, L. Gordon,Martino, Allison M.,Murty, Madhavi G.,Richardson, Stewart K.,Schroeder, Joseph D.,Shumway, Matthew J.,Tam, S. William,Trocha, A. Mark,Young, Delano V.
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p. 2180 - 2193
(2007/10/03)
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