- SUBSTITUTED PYRROLOPYRIDINES AS JAK INHIBITORS
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The present invention relates to new pyrrolopyridine compounds having the structures of Formula (I)-(IV), wherein the R groups, A, B, C, D and n are as defined in the detailed description, and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibition of JAK kinase activity in a human or animal subject are also provided for the treatment diseases such as pruritus, alopecia, androgenetic alopecia, alopecia areata, vitiligo and psoriasis.
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Paragraph 0328; 0329
(2020/11/12)
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- Preparation method of 3-substituted-5-aminopiperidine with protecting group
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The invention provides a preparation method of 3-substituted-5-aminopiperidine with a protecting group, and particularly provides a preparation method of 3-substituted-5-aminopiperidine with a protecting group, which has the advantages of low cost and easily available raw materials and reaction reagents.
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- Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans
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Significant work has been dedicated to the discovery of JAK kinase inhibitors resulting in several compounds entering clinical development and two FDA approved NMEs. However, despite significant effort during the past 2 decades, identification of highly s
- Thorarensen, Atli,Dowty, Martin E.,Banker, Mary Ellen,Juba, Brian,Jussif, Jason,Lin, Tsung,Vincent, Fabien,Czerwinski, Robert M.,Casimiro-Garcia, Agustin,Unwalla, Ray,Trujillo, John I.,Liang, Sidney,Balbo, Paul,Che, Ye,Gilbert, Adam M.,Brown, Matthew F.,Hayward, Matthew,Montgomery, Justin,Leung, Louis,Yang, Xin,Soucy, Sarah,Hegen, Martin,Coe, Jotham,Langille, Jonathan,Vajdos, Felix,Chrencik, Jill,Telliez, Jean-Baptiste
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p. 1971 - 1993
(2017/03/20)
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- POLYCYCLIC TLR7/8 ANTAGONISTS AND USE THEREOF IN THE TREATMENT OF IMMUNE DISORDERS
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The present invention relates to compounds of Formula (I) and pharmaceutically acceptable compositions thereof, useful as toll-like receptor 7/8 (TLR7/8) antagonists. In Formula (I), Ring A is aryl or heteroaryl; Ring B is aryl or heteroary; and X is C(R4)2, O, NR4, S, S(R4), or S(R4)2.
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- BICYCLIC HETEROAROMATIC CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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The present disclosure describes bicyclic heteroaromatic carboxamide derivatives of formula (I), as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.
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Page/Page column 85
(2016/02/26)
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- PYRIDINEAMINE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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The present disclosure describes pyridineamine compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer, immune disorders and other diseases. Formula (I).
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Page/Page column 67
(2016/12/22)
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- BICYCLIC AROMATIC CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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The present disclosure describes bicyclic aromatic carboxamide derivatives, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.
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Paragraph 0328
(2016/03/01)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE
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Disclosed herein are reversible and irreversible inhibitors of Bruton's tyrosine kinase (Btk). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are describeded, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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- Discovery of imidazopyridazines as potent Pim-1/2 kinase inhibitors
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High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted in the discovery of a series of imidazopyridazine-based Pim inhibitors exemplified by compound 22m, which was found to be a subnanomolar inhibitor of the Pim-1 and Pim-2 isoforms (IC50values of 0.024?nM and 0.095?nM, respectively) and to potently inhibit the phosphorylation of BAD in a cell line that expresses high levels of all Pim isoforms, KMS-12-BM (IC50?=?28?nM). Profiling of Pim-1 and Pim-2 expression levels in a panel of multiple myeloma cell lines and correlation of these data with the potency of compound 22m in a proliferation assay suggests that Pim-2 inhibition would be advantageous for this indication.
- Wurz, Ryan P.,Sastri, Christine,D'Amico, Derin C.,Herberich, Brad,Jackson, Claire L.M.,Pettus, Liping H.,Tasker, Andrew S.,Wu, Bin,Guerrero, Nadia,Lipford, J. Russell,Winston, Jeffrey T.,Yang, Yajing,Wang, Paul,Nguyen, Yen,Andrews, Kristin L.,Huang, Xin,Lee, Matthew R.,Mohr, Christopher,Zhang,Reid, Darren L.,Xu, Yang,Zhou, Yihong,Wang, Hui-Ling
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p. 5580 - 5590
(2016/11/09)
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- FURO- AND THIENO-PYRIDINE CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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The present disclosure describes furo- and thieno-pyridine carboxamide compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.
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Paragraph 0778; 0779
(2015/03/04)
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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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- SELECTIVELY SUBSTITUTED QUINOLINE COMPOUNDS
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Embodiments of the disclosure relate to selectively substituted quinoline compounds of formula (I) that act as antagonists or inhibitors for Toll -like receptors 7 and/or 8, and their use in pharmaceutical compositions effective for treatment of systemic
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Paragraph 0236
(2015/05/05)
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- BICYCLIC AROMATIC CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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The present disclosure describes bicyclic aromatic carboxamide derivatives, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.
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Paragraph 0689; 0690
(2014/07/23)
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- THIAZOLECARBOXAMIDES AND PYRIDINECARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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The present disclosure describes thiazole and pyridine carboxamide derivatives, their compositions and methods of use. The compounds inhibit the activity of the Pim kinases and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.
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Paragraph 08285; 0829
(2014/07/23)
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- BICYCLIC PYRIDAZINE COMPOUNDS AS PIM INHIBITORS
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The invention relates to bicyclic compounds of formulas I and I', and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.
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- INHIBITORS OF JAK
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The present invention relates to the use of novel compounds of Formula I, wherein the variables m, n, p, q, Q, r, R, R′, X, X′, Y, Z1, Z2, and Z3 are defined as described herein, which inhibit JAK and are useful for the treatment of auto-immune and inflammatory diseases.
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Page/Page column 53
(2011/04/18)
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- Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors
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Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.
- Medina, Jesús R.,Becker, Christopher J.,Blackledge, Charles W.,Duquenne, Celine,Feng, Yanhong,Grant, Seth W.,Heerding, Dirk,Li, William H.,Miller, William H.,Romeril, Stuart P.,Scherzer, Daryl,Shu, Arthur,Bobko, Mark A.,Chadderton, Antony R.,Dumble, Melissa,Gardiner, Christine M.,Gilbert, Seth,Liu, Qi,Rabindran, Sridhar K.,Sudakin, Valery,Xiang, Hong,Brady, Pat G.,Campobasso, Nino,Ward, Paris,Axten, Jeffrey M.
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experimental part
p. 1871 - 1895
(2011/05/30)
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- HETEROARYL BTK INHIBITORS
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The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.
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- Bicyclic Kinase Inhibitors
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New compounds, compositions and methods of inhibition of Provirus Integration of Maloney Kinase (PIM kinase) activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one PIM kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.
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- Heterocyclic Kinase Inhibitors
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New compounds, compositions and methods of inhibition of Provirus Integration of Maloney Kinase (PIM kinase) activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one PIM kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.
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- STEREOSELECTIVE SYNTHESIS OF PIPERIDINE DERIVATIVES
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This invention relates to dialdehyde or dinitrile compounds, which are useful for stereoselective synthesis of piperidine, pyrrolidine, and azepane derivatives.
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Page/Page column 11
(2010/06/22)
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- Pyrrolopyrazinyl Urea Kinase Inhibitors
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The present invention relates to the use of novel pyrrolopyrazinyl urea derivatives of Formula I, wherein the variables R1, R2, R3, R4, and R5 are defined as described herein, which inhibit JAK and are useful for the treatment of auto-immune and inflammatory diseases.
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Page/Page column 44
(2010/06/19)
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- ANTIBIOTIC DRUG
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This invention relates to a malic acid salt of (3S, 5R)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid. Also disclosed is a method of treating bacterial infection by an effective amount of this salt.
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Page/Page column 8
(2010/04/03)
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- TREATMENT OF ANTIBIOTIC-RESISTANT BACTERIA INFECTION
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This invention relates to a method of treating infection by methicillin-nonsusceptibale bacteria, vancomycin-nonsusceptibale bacteria, penicillin-nonsusceptibale bacteria, clarithromycin-nonsusceptibale bacteria, or metronidazole-nonsusceptibale bacteria by administering to a subject in need thereof an effective amount of a compound of the following formula:
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- PNEUMONIA TREATMENT
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This invention relates to a method of treating pneumonia by orally administering to a subject in need thereof a quinolone compound of formula (I), shown in the disclosure, at a daily dose of 2-30 mg/kg.
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- Pim kinase inhibitors and methods of their use
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The present invention relates to new compounds of Formulas I and II, their tautomers, stereoisomers and polymorphs, and pharmaceutically acceptable salts, esters, metabolites or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the inhibition of Pim kinase activity and/or the prophylaxis or treatment of cancer.
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Page/Page column 24
(2010/09/05)
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- ANTIMICROBIAL PARENTERAL FORMULATION
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This invention relates to a parenteral formulation containing an effective amount of the compound of the following formula I: water, and an isotonic agent. Also disclosed is a method of treating an infectious disease by administering this formula to a subject via parenteral injection or infusion.
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- PIM KINASE INHIBITORS AND METHODS OF THEIR USE
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The present invention relates to new compounds of Formulas (I) and (II), their tautomers, stereoisomers and polymorphs, and pharmaceutically acceptable salts, esters, metabolites or prodrugs thereof, compositions of the new compounds together with pharmac
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- Malate salts, and polymorphs of (3S,5S)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid
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The present invention is directed to malate salts of (3S,5S)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid, and its polymorphs. The present invention is also directed to pharmaceutical compositions comprising the described salts and polymorphs.
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Page/Page column 6
(2008/06/13)
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- Coupling process for preparing quinolone intermediates
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Process for making 7-cycloamino-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acids. Borate ester compounds suitable for use in such process.
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Page/Page column 4; 5-6
(2008/06/13)
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- Hydride reduction process for preparing quinolone intermediates
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Hydride process for making acyclic diol intermediates from cyclic intermediates, useful in antibacterial quinolone synthesis.
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Page/Page column 3-4
(2008/06/13)
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- ANTIMICROBIAL QUINOLONES, THEIR COMPOSITIONS AND USES
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Compounds of the following formula (I) are effective antimicrobial agents.
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Page 103; 104-105
(2010/02/06)
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