- INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE
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Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic disorders, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.
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Paragraph 005; 006; 007
(2019/08/20)
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- Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists
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G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound 4 demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models.
- Shi, Jun,Gu, Zhengxiang,Jurica, Elizabeth Anne,Wu, Ximao,Haque, Lauren E.,Williams, Kristin N.,Hernandez, Andres S.,Hong, Zhenqiu,Gao, Qi,Dabros, Marta,Davulcu, Akin H.,Mathur, Arvind,Rampulla, Richard A.,Gupta, Arun Kumar,Jayaram, Ramya,Apedo, Atsu,Moore, Douglas B.,Liu, Heng,Kunselman, Lori K.,Brady, Edward J.,Wilkes, Jason J.,Zinker, Bradley A.,Cai, Hong,Shu, Yue-Zhong,Sun, Qin,Dierks, Elizabeth A.,Foster, Kimberly A.,Xu, Carrie,Wang, Tao,Panemangalore, Reshma,Cvijic, Mary Ellen,Xie, Chunshan,Cao, Gary G.,Zhou, Min,Krupinski, John,Whaley, Jean M.,Robl, Jeffrey A.,Ewing, William R.,Ellsworth, Bruce Alan
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p. 681 - 694
(2018/02/16)
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- Azabenzimidazole derivative having AMPK-activating activity
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Disclosed is a compound which is useful as an AMPK activator. A compound represented by formula: or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen, or substituted or unsubstituted alkyl, R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl or the like, with the proviso that R1, R2 and R3 are not simultaneously hydrogen, X is a single bond, —S—, —O—, —NR5—, —C(═O)— or the like, R5 is hydrogen, or substituted or unsubstituted alkyl, Y is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl or the like.
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Page/Page column 55
(2017/03/08)
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- Synthesis and Minisci reactions of organotrifluoroborato building blocks
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Copper-catalyzed borylation of a variety of organic halides with bis(pinacolato)diboron allows the preparation of diverse potassium organotrifluoroborates. The reactions are mild and general, providing access to a variety of interesting, boron-containing
- Presset, Marc,Fleury-Bregeot, Nicolas,Oehlrich, Daniel,Rombouts, Frederik,Molander, Gary A.
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p. 4615 - 4619
(2013/06/04)
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- 1H-[1,2,3]TRIAZOLO[4,5-c]PYRIDINE-4-CARBONITRILE DERIVATIVES
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The invention relates to 1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile derived Cathepsin S inhibitors of Formula (I), wherein R1 is H or (C1-3)alkyl; R2 is halogen or (C1-4)alkyl, optionally substituted with one or more halogens; n is 1 -3; X is O or CH2; U, V and W are CH; or one of U, V and W is N; Y is a group capable of interacting with the Sn....S2 substites of the active site of Cathepsin S; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same as well as to the use of these derivatives for the preparation of a medicament for the treatment of cathepsin S related diseases such as atherosclerosis, obesity, inflammation and immune disorders, such as rheumatoid arthritis, psoriasis, cancer, and chronic pain, such as neuropathic pain.
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Page/Page column 36; 37
(2011/08/04)
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- ACETYLENE DERIVATIVES AS STEAROYL COA DESATURASE INHIBITORS
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The present invention provides Stearoyl CoA Desaturase (SCD) inhibitors, hi particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase 1 (SCD 1) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by Stearoyl CoA Desaturase (SCD) inhibitors.
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Page/Page column 63
(2008/12/05)
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- Novel euglycemic and hypolipidemic agents. 4. Pyridyl- and quinolinyl- containing thiazolidinediones
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A series of substituted pyridyl- and quinolinyl-containing 2,4- thiazolidinediones having interesting cyclic amine as a linker have been synthesized. Both unsaturated thiazolidinediones 5 and saturated thiazolidinediones 6 and their various salts were evaluated in db/db mice for euglycemic and hypolipidemic effects and compared with BRL compound 11 and BRL-49653, respectively. Some of the potent compounds were converted to various salts in order to obtain improved activities. Among all the salts evaluated, the maleate salt of unsaturated TZD 5a was found to be a very potent euglycemic and hypolipidemic compound. Some of the more interesting compounds have also been evaluated in ob/ob mice and compared with rosiglitazone (maleate salt of BRL-49653). Oral glucose tolerance tests were performed in both db/db and ob/ob mice. Pharmacokinetic studies of 5a maleate are also reported. Receptor binding studies of PPARγ by 5a/5a maleate did not show any significant transactivation of PPARα or PPARγ.
- Lohray,Bhushan, Vidya,Reddy, A. Sekar,Rao, P. Bheema,Reddy, N. Jaipal,Harikishore,Haritha,Vikramadityan, Reeba K.,Chakrabarti, Ranjan,Rajagopalan,Katneni
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p. 2569 - 2581
(2007/10/03)
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- Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them
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Novel antidiabetic compounds, their tautomeric forms, their derivatives, their steroisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceuticaly acceptable compositions containing them; methods for preparing the antidiabetic compounds and their uses.
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