- Solid dispersions containing an apoptosis-inducing agent
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A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound of Formula I as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises dissolving the compound, the polymeric carrier and the surfactant in a suitable solvent, and removing the solvent to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.
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- Aryl substituted aminotetrahydropyran compound and use thereof
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The invention relates to an aryl substituted aminotetrahydropyran compound and use thereof, and further relates to a pharmaceutical composition comprising the compound. The compound or pharmaceuticalcomposition provided by the invention can be used as a dipeptidyl peptidase-IV (DPP-IV) inhibitor.
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Paragraph 0250; 0252; 0253; 0254
(2019/07/04)
-
- Design, synthesis, and evaluation of novel and selective G-protein coupled receptor 120 (GPR120) spirocyclic agonists
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Type 2 diabetes mellitus (T2DM) is an ever increasing worldwide epidemic, and the identification of safe and effective insulin sensitizers, absent of weight gain, has been a long-standing goal of diabetes research. G-protein coupled receptor 120 (GPR120) has recently emerged as a potential therapeutic target for treating T2DM. Natural occurring, and more recently, synthetic agonists have been associated with insulin sensitizing, anti-inflammatory, and fat metabolism effects. Herein we describe the design, synthesis, and evaluation of a novel spirocyclic GPR120 agonist series, which culminated in the discovery of potent and selective agonist 14. Furthermore, compound 14 was evaluated in vivo and demonstrated acute glucose lowering in an oral glucose tolerance test (oGTT), as well as improvements in homeostatic measurement assessment of insulin resistance (HOMA-IR; a surrogate marker for insulin sensitization) and an increase in glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp in diet-induced obese (DIO) mice.
- Cox, Jason M.,Chu, Hong D.,Chelliah, Mariappan V.,Debenham, John S.,Eagen, Keith,Lan, Ping,Lombardo, Matthew,London, Clare,Plotkin, Michael A.,Shah, Unmesh,Sun, Zhongxiang,Vaccaro, Henry M.,Venkatraman, Srikanth,Suzuki, Takao,Wang, Nengxue,Ashley, Eric R.,Crespo, Alejandro,Madeira, Maria,Leung, Dennis H.,Alleyne, Candice,Ogawa, Aimie M.,Souza, Sarah,Thomas-Fowlkes, Brande,Di Salvo, Jerry,Weinglass, Adam,Kirkland, Melissa,Pachanski, Michele,Powles, Mary Ann,Tozzo, Effie,Akiyama, Taro E.,Ujjainwalla, Feroze,Tata, James R.,Sinz, Christopher J.
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supporting information
p. 49 - 54
(2017/12/12)
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- SUBSTITUTED SPIROPIPERIDINYL COMPOUNDS USEFUL AS GPR120 AGONISTS
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The present invention relates to a compound represented by formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, inflammation related disorders, and related diseases and conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR120. Pharmaceutical compositions and methods of treatment are also included.
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Page/Page column 36; 39
(2014/05/07)
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- TETRAHYDROPYRAZOLOPYRIMIDINE COMPOUNDS
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Embodiments of the disclosure relate to tetrahydropyrazolopyrimidine compounds 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 lupus erythematosus (SLE) and lupus nephritis
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Paragraph 0499
(2014/01/07)
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- SUBSTITUTED ACETYL-COA CARBOXYLASE INHIBITORS
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The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R1, R2 and R3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.
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Page/Page column 17-18
(2012/11/07)
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- Synthesis of 7-oxo-dihydrospiro[indazole-5,4′-piperidine] acetyl-CoA carboxylase inhibitors
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Synthesis of oxo-dihydrospiroindazole-based acetyl-CoA carboxylase (ACC) inhibitors is reported. The dihydrospiroindazoles were assembled in a regioselective manner in six steps from substituted hydrazines and protected 4-formylpiperidine. Enhanced regios
- Bagley, Scott W.,Southers, James A.,Cabral, Shawn,Rose, Colin R.,Bernhardson, David J.,Edmonds, David J.,Polivkova, Jana,Yang, Xiaojing,Kung, Daniel W.,Griffith, David A.,Bader, Scott J.
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experimental part
p. 1497 - 1506
(2012/03/26)
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- N1-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
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The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of the compound, wherein R1, R2, R3 and R4 are as described herein; pharmaceutical compositions there-of; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl- CoA carboxylase enzyme(s) in an animal
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Page/Page column 21; 22
(2011/05/16)
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- N2-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
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The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of said compound, wherein R1, R2, R3 and R4 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl- CoA carboxylase enzyme(s) in an animal.
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Page/Page column 42; 43
(2011/06/16)
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- Substituted Disulfonamide Compounds
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Substituted disulfonamide compounds corresponding to formula I: In which R1, R2, R3, R4a, R4b, R5a, R5b, R8, R9a, R9b, R10, R11, a, b, s, t and A have defined meanings, pharmaceutical compositions containing one or more such compounds, processes for preparing such compounds, and a method of using such compounds for the treatment or inhibition of pain and/or other conditions mediated by the bradykinin receptor 1 (BR1).
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Page/Page column 31
(2010/06/22)
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- Substituted Indole Compounds
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Substituted indole compounds corresponding to the formula I: In which R8, R9a, R9b, R10, R11, R200, R210, A, D, T, q, s and t have defined meanings, processes for the preparation thereof, pharmaceutical compositions containing such compounds and the use of substituted indole compounds for the treatment or inhibition of pain and other conditions which are at least partly mediated by Bradykinin 1 receptors (B1R).
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Page/Page column 57
(2010/09/07)
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- Substituted Spiroamide Compounds
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Substituted spiroamide compounds corresponding to formula (I): wherein A, B, Q1, Q2, Q3, Q4, R1, R8, R9a, R9b, R12, R13, R200 and R210 have defined meanings, processes for their preparation, pharmaceutical compositions containing such compounds, and the use of such compounds for treating or inhibiting pain or other conditions mediated at least in part by the bradykinin 1 receptor (B1R).
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Page/Page column 41
(2010/09/18)
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- Substituted Spiro-amide Compounds
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Substituted spiro-amide compounds corresponding to formula I in which R5 through R8, D, X, Y and Z have defined meanings, processes for preparing such spiro-amide compounds, pharmaceutical compositions containing such compounds, and methods of using such spiro-amide compounds for treating and/or inhibiting disorders or disease states mediated at least in part by the bradykinin 1 receptor.
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Page/Page column 120
(2010/10/19)
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- SUBSTITUTED BENZIMIDAZOLES, BENZOTHIAZOLES AND BENZOXAZOLES
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The present invention relates to substituted benzimidazoles, benzothiazoles and benzoxazoles, processes for their preparation, medicaments containing these compounds and the use of these compounds for the preparation of medicaments.
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Page/Page column 143-144
(2010/12/29)
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- Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 2: Design of potent antagonists containing the 3-azaspiro[5.5]undec-9-yl template
-
The synthesis and biological activity of novel glycoprotein IIb-IIIa anatagonists containing 3-azaspiro[5.5]undec-9-yl nucleus are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the monoaza
- Pandey,Seroogy,Volkots,Smyth,Rose,Mehrotra,Heath,Ruhter,Schotten,Scarborough
-
p. 1293 - 1296
(2007/10/03)
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- Spiro compounds as inhibitors of fibrinogen-dependent platelet aggregation
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This invention relates to certain spirocyclic compounds substituted with both basic and acidic functionality, as shown by formula (I): wherein Q, L, Ai, Bj, R0, R3, R10, m, n, p and q are as defined in the disclosure, which are useful in inhibiting of platelet aggregation.
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