- METHODS OF TREATING NEURODEGENERATIVE DISEASES
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Described herein are methods of treating or preventing an ASK1 or DYRK1A associated disease, disorder, or condition comprising administering to a subject in need thereof a dual inhibitor of ASK1 and DYRK1A; including administering pharmaceutically acceptable salts and solvates thereof.
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Paragraph 0194
(2020/03/23)
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- ASK1 INHIBITOR COMPOUNDS AND USES THEREOF
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Described herein are compounds, including pharmaceutically acceptable salts and solvates thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat non-alcoholic steatohepatitis and other diseases characterized by dysfunctional tissue healing and fibrosis.
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Paragraph 0182
(2019/07/20)
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- New tetracyclic compound
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The invention relates to a new tetracyclic compound. The tetracyclic compound has a structure shown in the formula (III) and can be used as a bromine domain and additional terminal (BET) inhibitor. The invention further relates to synthesis and application of the compounds in disease treatment. More specifically, the invention relates to a fused heterocyclic derivative used as a BET inhibitor, a method for the preparation of these compounds, and a disease and symptom treatment method conductive to inhibition of one or more BET bromine domains.
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Paragraph 0393-0397
(2019/11/14)
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- COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF
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The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1α, GSPT1, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.
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Paragraph 0358
(2018/07/04)
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- 7-(MORPHOLINYL)-2-(N-PIPERAZINYL) METHYL THIENO [2, 3-C] PYRIDINE DERIVATIVES AS ANTICANCER DRUGS
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The present invention relates to novel series of substituted 7-(morpholinyl)-2-(N-piperazinyl)-methyl thieno [2, 3-c] pyridines of the following structure of formula I. Where in R1, R2, R3 and R4 are defined.
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- HETEROARYL COMPOUNDS AS BTK INHIBITORS AND USES THEREOF
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The present invention relates to imidazo pyridine compounds, and pharmaceutically acceptable compositions thereof, useful as BTK inhibitors.
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Paragraph 0512
(2016/05/02)
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- (2,4-dihydroxy-5-isopropylphenyl)(4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)ketone derivative, preparation and uses thereof
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The present invention discloses a (2,4-dihydroxy-5-isopropylphenyl)(4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)ketone derivative, preparation and uses thereof, and particularly relates to a (2,4-dihydroxy-5-isopropylphenyl)(4,6-dihydro-5H-thieno[2,3-c]pyrrol
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Paragraph 0106; 0107; 0108
(2016/10/08)
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- BIARYL COMPOUNDS USEFUL FOR THE TREATMENT OF HUMAN DISEASES IN ONCOLOGY, NEUROLOGY AND IMMUNOLOGY
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The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
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Paragraph 0160; 0164
(2015/06/25)
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- PYRIDINONES/PYRAZINONES, METHOD OF MAKING, AND METHOD OF USE THEREOF
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Pyridone and pyrazinone compounds of Formula (I) including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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- MST1 KINASE INHIBITORS AND METHODS OF THEIR USE
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Compounds for the inhibition of mammalian Ste20-like kinase 1 (MST1) are disclosed, along with compositions comprising them and methods of their use in the treatment, management or prevention of an inflammatory or autoimmune diseases or disorders.
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Page/Page column 13
(2012/09/11)
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- PHOSPHOTHIOPHENE AND PHOSPHOTHIAZOLE HCV POLYMERASE INHIBITORS
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Provided herein are phosphothiophene and phosphothiazole compounds, for example, of any of Formulae I, IA, HA, IIIA, IVA, VA, VIA, VIIA, IB, HB, IIIB, IVB, VB, VIB and VIIB disclosed herein, pharmaceutical compositions comprising the compounds, and proces
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Page/Page column 168; 169
(2010/09/18)
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- Synthesis and pharmacological characterization of N3-substituted willardiine derivatives: Role of the substituent at the 5-position of the uracil ring in the development of highly potent and selective GLUK5 kainate receptor antagonis
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Some N3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-sub
- Dolman, Nigel P.,More, Julia C. A.,Alt, Andrew,Knauss, Jody L.,Pentik?inen, Olli T.,Glasser, Carla R.,Bleakman, David,Mayer, Mark L.,Collingridge, Graham L.,Jane, David E.
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p. 1558 - 1570
(2007/10/03)
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- IMIDAZOLOPYRAZINE COMPOUNDS USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES
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Novel imidazo[1,2-a]pyrazine compounds are disclosed that have a formula ( I ) represented by the following:The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, arthritis, inflammation, and others.
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Page/Page column 98
(2008/06/13)
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- Structure-activity relationship studies on N3-substituted willardiine derivatives acting as AMPA or kainate receptor antagonists
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N3-Substitution of the uracil ring of willardiine with a variety of carboxyalkyl or carboxybenzyl substituents produces AMPA and kainate receptor antagonists. In an attempt to improve the potency and selectivity of these AMPA and kainate receptor antagonists a series of analogues with different terminal acidic groups and interacidic group spacers was synthesized and pharmacologically characterized. (5′)-1-(2-Amino-2-carboxyethyl)-3-(2- carboxythiophene-3-ylmethyl)pyrimidine-2,4-dione (43, UBP304) demonstrated high potency and selectivity toward native GLUK5-containing kainate receptors (KD 0.105 ± 0.007 μM vs kainate on native GLUK5; KD 71.4 ± 8.3 μM vs (S)-5- fluorowillardiine on native AMPA receptors). On recombinant human GLU K5, GLUK5/GLUK6, and GLUK5/GLU K2, KB values of 0.12 ± 0.03, 0.12 ± 0.01, and 0.18 ± 0.02 μM, respectively, were obtained for 43. However, 43 displayed no activity on homomeric GLUK6 or GLUK7 kainate receptors or homomeric GLUA1-4 AMPA receptors (IC50 values > 100 μM). Thus, 43 is a potent and selective GLUK5 receptor antagonist.
- Dolman, Nigel P.,More, Julia C. A.,Alt, Andrew,Knauss, Jody L.,Troop, Helen M.,Bleakman, David,Collingridge, Graham L.,Jane, David E.
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p. 2579 - 2592
(2007/10/03)
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- TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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The present invention relates to tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. More precisely, the present invention relates to tricyclic derivatives as colchicine derivatives, pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. Tricyclic derivatives of the present invention show very powerful cytotoxicity to cancer cell lines but were much less toxic than colchicine or taxol, confirmed through animal toxicity test. Tricyclic derivatives of the invention also decrease the volume and weight of a tumor and have a strong angiogenesis inhibiting activity in HUVEC cells. Thus, tricyclic derivatives of the present invention can effectively be used as an anticancer agent, anti-proliferation agent and an angiogenesis inhibitor.
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- Aminomethylthiophene-2-carboxylic acids as dipeptide mimetic in new growth hormone secretagogues
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3-Aminomethylbenzoic acid is a well established dipeptide mimetic. Herein, aminomethylthiophene-2-carboxylic acids have been synthesized as analogues of 3-aminomethylbenzoic acid. Their use as a dipeptide-mimetic at the N-terminal of novel growth hormone secretagogues is described.
- Peschke, Bernd,Madsen, Kjeld,Hansen, Birgit Sehested,Johansen, Nils Langeland
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p. 1969 - 1972
(2007/10/03)
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- Synthesis of Conformationally-Constrained Glutamate Analogues of the Antitumor Agents DDATHF, LY254155, and LY231514
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Analogues of the active antitumor agents DDATHF (4), LY254155 (11), and LY231514 (14) have been prepared in which the rotational flexibility of the benzoylglutamate amide linkage is constrained by incorporation of a methylene bridge between the glutamate amide nitrogen and the ortho position of the aromatic ring. Evaluation of the resulting isoindolinones as in vitro inhibitors of the growth of CCRF-CEM cells revealed that, although some analogues retained activity, in no case was cytotoxicity enhanced, and in some cases it was substantially reduced.
- Taylor, Edward C.,Jennings, Lee D.,Mao, Zhenmin,Hu, Baihua,Jun, Jong-Gab,Zhou, Ping
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p. 5392 - 5403
(2007/10/03)
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- N-3-Substituted Pyrimidones as Potent, Orally Active, AT1 Selective Angiotensin II Receptor Antagonists
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A novel series of nonpeptide angiotensin II (A II) antagonists containing a pyrimidinone ring which carries a C-linked biphenyltetrazole moiety and a carboxyheteroaryl group on the 3-position have been prepared.Their affinity for the AT1 receptor was determined in a binding assay on rat adrenal cortical membranes.The in vivo antihypertensive properties were tested by evaluating the inhibition of the pressor response to A II followed by iv and id administration.Extensive molecular modeling studies, including comparison of molecular electrostatic potential distributions, conformational analysis, and overlays on a computational pharmacophore model of A II, were used to evaluate structural parameters of the new compounds, in comparison to other known A II antagonists (e.g., DUP-753 and SKandF 108566).According to the modeling studies, the introduction of a (carboxyheteroaryl)methyl moiety at the 3-position of the pyrimidinone ring led to derivatives with increased potency.Methyl 2-methyl>-1-(6H)-pyrimidinyl>methyl>-3-thiophenecarboxylate (3k, LR-B/081), one of the most potent compounds in the series (Ki = 1.4 nM), exhibited a marked antihypertensive activity on oral administration to conscious renal hypertensive rats, with long duration of action.It was selected for clinical evaluation in the treatment of hypertension in man.
- Salimbeni, Aldo,Canevotti, Renato,Paleari, Fabio,Poma, Davide,Caliari, Saturnino,et al.
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p. 4806 - 4820
(2007/10/03)
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- A New Synthesis of Benzothiophenes and Benzothiophenes by Annulation of Disubstituted Thiophenes
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Nine newly prepared ortho-disubtituted thiophenes (1-5) react with Michael acceptors to form benzo- and benzothiophenes.This novel annulation process is specifically suited to form benzothiophenes with substituents in the benzene moiety.Substitution
- Terpstra, Jan W.,Leusen, Albert M. van
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p. 230 - 238
(2007/10/02)
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- SYNTHESIS OF QUINOLINE AND BENZOTHIOPHENE DERIVATIVES BY RING ANNELATION OF PYRIDINES AND THIOPHENES
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Selected ortho-disubstituted pyridines and thiophenes react with Michael acceptors to give functionalized quinolines or benzothiophenes, respectively.
- Leusen, Albert M. van,Terpstra, Jan Willem
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p. 5097 - 5100
(2007/10/02)
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