- Polycyclic amide derivative as CDK9 inhibitor, and preparation method and application thereof
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The invention belongs to the technical field of polycyclic amide derivatives, and particularly relates to a polycyclic amide derivative as a CDK9 inhibitor, and a preparation method and application thereof. The polycyclic amide derivative shows excellent CDK9 enzyme inhibitory activity, and can be used for preparing drugs for treating cancers, especially hematologic cancers including acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, follicular lymphoma and the like and solid tumors, such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia and follicular lymphoma, including breast cancer, prostate cancer, ovarian cancer, hepatocellular carcinoma, pancreatic cancer, kidney cancer, stomach cancer, colorectal cancer, lung cancer and the like.
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Paragraph 0265-0267; 0270-0272
(2021/07/24)
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- SMALL MOLECULE INHIBITORS OF THE JAK FAMILY OF KINASES
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2-((1r,4r)-4-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)cyclohexyl)acetonitrile compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions mediated by JAK.
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Page/Page column 56; 57
(2020/01/08)
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- Small Molecule Inhibitors of the JAK Family of Kinases
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2-((1r,4r)-4-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)cyclohexyl)acetonitrile compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions mediated by JAK, such as inflammatory bowel disease.
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Paragraph 0188
(2018/07/05)
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- IMIDAZOPYRROLOPYRIDINE AS INHIBITORS OF THE JAK FAMILY OF KINASES
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2-((1r,4r)-4-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)cyclohexyl)acetonitrile compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions mediated by JAK, such as inflammatory bowel disease.
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Page/Page column 174
(2018/07/05)
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- BENZAMIDE IMIDAZOPYRAZINE BTK INHIBITORS
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Provided are Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula I, pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, or their use in therapy.
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Page/Page column 113
(2016/07/27)
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- TERTIARY ALCOHOL IMIDAZOPYRAZINE BTK INHIBITORS
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Provided are Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, or their use in therapy.
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Page/Page column 64
(2016/08/03)
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- BIARYLETHER IMIDAZOPYRAZINE BTK INHIBITORS
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The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), or pharmaceutically acceptable salts thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds of Formula (I) in the treatment of Btk mediated disorders.
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Page/Page column 47
(2016/07/27)
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- SUBSTITUTED DIAMINOCARBOXAMIDE AND DIAMINOCARBONITRILE PYRIMIDINES, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Provided herein are Diaminopyrimidine Compounds having the following structures: wherein R1, R2, R3, and R4 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidine Compound, and methods for treating or preventing liver fibrotic disorders or a condition treatable or preventable by inhibition of a JNK pathway.
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Page/Page column 179; 180
(2012/11/07)
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- Design, synthesis, radiolabeling, and in vitro and in vivo evaluation of bridgehead iodinated analogues of N -{2-[4-(2-methoxyphenyl)piperazin-1-yl] ethyl}- N -(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635) as potential SPECT ligands for the 5-HT1A receptor
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Here we describe the design, synthesis, and pharmacological profile of 5-HT1A receptor ligands related to 1 (WAY-100635). The cyclohexyl moiety in 1 and its O-desmethylated analogue 3 were replaced by the bridgehead iodinated bridge-fused rings: adamantyl, cubyl, bicyclo[2.2.2]octyl, or bicyclo[2.2.1]heptyl. All analogues displayed a (sub)nanomolar affinity for the 5-HT1A receptor in vitro. Compounds 6b and 7b appeared to be selective for this receptor over other relevant receptors and could easily be iodinated with radioactive iodine-123. In humane hepatocytes, [ 123I]6b showed a low propensity for amide hydrolysis and a stable carbon-iodine bond. The biodistribution of [123I]6b and [ 123I]7b in rats revealed that the carbon-iodine bond was also stable in vivo. Unfortunately, the brain uptake and the specificity for both radioligands were significantly lower than those of the parent molecule 1. In conclusion, the designed tracers are not suitable for SPECT imaging.
- Al Hussainy, Rana,Verbeek, Joost,Van Der Born, Dion,Braker, Anton H.,Leysen, Josée E.,Knol, Remco J.,Booij, Jan,Herscheid
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supporting information; experimental part
p. 3480 - 3491
(2011/07/07)
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- HETEROBICYCLIC METALLOPROTEASE INHIBITORS
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The present invention relates generally to amide group containing pharmaceutical agents, and in particular, to amide containing heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic MMP- 13 inhibiting compounds, that exhibit an increased potency in relation to currently known MMP- 13 inhibitors.
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Page/Page column 167
(2008/06/13)
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- Ruthenium catalysed oxidation without CCl4 of oleic acid, other monoenic fatty acids and alkenes
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Ruthenium catalysed oxidation of alkenes and monoenic fatty acids is reported. The study of the influence of cosolvents (H2O/MeCN/X) shows that toxic CCl4 initially used in the Sharpless system (H 2O/MeCN/CCl4) can be avoided and demonstrates that the oxidative cleavage of CC bond could be accomplished in good yields with H 2O/MeCN/AcOEt solvent system in a ratio 3/2/2, respectively.
- Zimmermann, Fran?ois,Meux, Eric,Mieloszynski, Jean-Luc,Lecuire, Jean-Marie,Oget, Nicolas
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p. 3201 - 3203
(2007/10/03)
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- Synthesis of Bridgehead-Bridgehead Substituted Bicycloalkanes
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A convenient synthetic route to several bicycloalkanes bearing substitution at both bridgehead positions is described.The two-step procedure, which involves alkylation of the monoenolates of readily available cyclohexane diesters with 1,2-dihaloethane followed by a base-inducted cyclization of the derived haloethylated product, was successfully applied to the synthesis of dimethyl bicyclooctane-1,4-dicarboxylate, dimethyl bicycloheptane-1,4-dicarboxylate and dimethyl bicyclooctane-1,5-dicarboxylate.Additionally, it was found that the two latter diesters could be obtained in quite acceptable yields in a one-pot procedure through their corresponding cyclohexyl bisenolate precursors.
- Della, Ernest W.,Tsanaktsidis, John
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p. 1705 - 1718
(2007/10/02)
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