354
Views
2
CrossRef citations to date
0
Altmetric
Review

GPR119 agonists for the treatment of type 2 diabetes: an updated patent review (2014-present)

, ORCID Icon, & ORCID Icon
Pages 795-808 | Received 07 Jan 2021, Accepted 20 Apr 2021, Published online: 10 May 2021

References

  • Li N, Wang LJ, Jiang B, et al. Recent progress of the development of dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus. Eur J Med Chem. 2018;151:145–157.
  • Fang Y, Yang Z, Gundeti S, et al. Novel 5-nitropyrimidine derivatives bearing endo-azabicyclic alcohols/amines as potent GPR119 agonists. Bioorg Med Chem. 2017;25:254–260.
  • IDF diabetes atlas 9th edition, 2019. [cited 2020 Dec 20]. Available from: https://diabetesatlas.org/en/[Last
  • Boehm M, Crawford M, Moscovitz JE, et al. Diabetes area patent participation analysis – part II: years 2011-2016. Expert Opin Ther Pat. 2018;28:111–122.
  • Matsuda D, Kawamura M, Kobashi Y, et al. Design, synthesis and biological evaluation of novel 7-azaspiro[3.5]nonane derivatives as GPR119 agonists. Bioorg Med Chem. 2018;26:1832–1847.
  • Yu CG, Fu Y, Fang Y, et al. Fighting type-2 diabetes: present and future perspectives. Curr Med Chem. 2019;26:1891–1907.
  • Yang Z, Fang Y, Park H. Synthesis and biological evaluation of pyrimidine derivatives with diverse azabicyclic ether/amine as novel GPR119 agonist. Bioorg Med Chem Lett. 2017;27:2515–2519.
  • Kang SU. GPR119 agonists: a promising approach for T2DM treatment? A SWOT analysis of GPR119. Drug Discov Today. 2013;18:1309–1315.
  • Ohishi T, Yoshida S. The therapeutic potential of GPR119 agonists for type 2 diabetes. Expert Opin Inv Drug. 2012;21:321–328.
  • Overton HA, Fyfe MCT, Reynet C. GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Br J Pharmacol. 2008;153:S76–81.
  • Fredriksson R, Höglund PJ, Gloriam DE, et al. Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett. 2003;554:381–388.
  • Shah U, Kowalski TJ. GPR119 agonists for the potential treatment of type 2 diabetes and related metabolic disorders. Vitam Horm. 2010;84:415–448.
  • Odori S, Hosoda K, Tomita T, et al. GPR119 expression in normal human tissues and islet cell tumors: evidence for its islet-gastrointestinal distribution, expression in pancreatic beta and alpha cells, and involvement in islet function. Metabolism. 2013;62:70–78.
  • Little TJ, Isaacs NJ, Young RL, et al. Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index. Am J Physiol Gastrointest Liver Physiol. 2014;307:G958–967.
  • Dhayal S, Morgan NG. The significance of GPR119 agonists as a future treatment for type 2 diabetes. Drug News Perspect. 2010;23:418–424.
  • Chepurny OG, Holz GG, Roe MW, et al. GPR119 agonist AS1269574 activates TRPA1 cation channels to stimulate GLP-1 secretion. Mol Endocrinol. 2016;30:614–629.
  • Jones RM, Leonard JN. The emergence of GPR119 agonists as anti-diabetic agengs. Annu Rep Med Chem. 2009;44:149–170.
  • Li NX, Brown S, Kowalski T, et al. GPR119 agonism increases glucagon secretion during insulin-induced hypoglycaemia. Diabetes. 2018;67:1401–1413.
  • Overton HA, Babbs AJ, Doel SM, et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 2006;3:167–175.
  • Chu ZL, Carroll C, Chen R, et al. N-oleoyldopamine enhances glucose homeostasis through the activation of GPR119. Mol Endocrinol. 2010;24:161–170.
  • Syed SK, Bui HH, Beavers LS, et al. Regulation of GPR119 receptor activity with endocannabinoid-like lipids. Am J Physiol Endocrinol Metab. 2012;303:E1469–E1478.
  • Moran BM, Abdel-Wahab YHA, Flatt PR, et al. Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice. Biol Chem. 2014;395:453–464.
  • Kleberg K, Hassing HA, Hansen HS. Classical endocannabinoid-like compounds and their regulation by nutrients. BioFactors. 2014;40:363–372.
  • Ritter K, Buning C, Halland N, et al. G protein-coupled receptor 119 (GPR119) agonists for the treatment of diabetes: recent progress and prevailing challenges. J Med Chem. 2016;59:3579–3592.
  • Semple G, Fioravanti B, Pereira G, et al. Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119. J Med Chem. 2008;51(17):5172–5175.
  • Fevig JM, Wacker DA [6,6] and [6,7]-bicyclic GPR119 G protein-coupled receptor agonists. WO2008137435. 2008.
  • Neelamkavi SF, Boyle CD, Harris JM, et al. Bicyclic heterocycle derivatives and their use as GPCR modulators. WO2010009207. 2010.
  • Neustadt BR, Stamford A, Hao J, et al. Pyrimidine derivatives as GPCR modulators for use in the treatment of obesity and diabetes. WO2010075269. 2010.
  • Neelamakavil SF, Boyle CD, Chackalamannil S, et al. Bicyclic heterocycle derivatives and use thereof as GPR119 modulators. WO2010009195. 2010.
  • Heckel A, Himmelsbach F, Langkopf E, et al. Substituted piperidines as GPR119 modulators for the treatment of metabolic disorders. WO2012168315A1. 2012.
  • Jones RM, Buzard DJ, Han S, et al. Modulators of the GPR119 receptor and the treatment of disorders related thereto. WO2012170702. 2012.
  • Darout E, Guimaraes C, Mascitti V, et al. GPR119 modulators. WO2013011402. 2013.
  • Fell JB, Fischer JP, Hinklin RJ Piperidinyl-substituted cyclic ureas as gpr119 modulators. US20140309226. 2014.
  • Broekema M, Wu G, Wacker DA Pyrimidinylpiperidinyloxypyridone analogues as gpr119 modulators. US9174965. 2015.
  • Shintani Y, Niwa M, Monma S, et al. Preparation of substituted azole compounds as GPR119 agonists for the treatment of diabetes and obesity. JP2017119628. 2017.
  • Mansour TS, Chafeev M, Yudin M, et al. Compounds containing benzo[d][1,3]oxathiole, benzo[d][1,3]oxathiole 3-oxide or benzo[d][1,3]oxathiole 3,3-dioxide and methods/uses thereof as agonists of g protein-coupled receptor 119. WO2017210794. 2017.
  • Patil RI, Gunjal AP, Verma J, et al. Preparation of heterocyclic compounds as GPR119 agonist for treatment of metabolic disorders. WO2017175066. 2017.
  • Patil RI, Verma J, Shah D, et al. Preparation of thiazolopyridine derivatives as GPR119 agonists for treatment of metabolic disorders. WO2017175068. 2017.
  • Jones RM, Leonard JN, Buzard DJ, et al. GPR119 agonists for the treatment of type 2 diabetes. J Expert Opin Ther Pat. 2009;19:1339–1359.
  • Fyfe MC, McCormack JG, Overton HA, et al. GPR119 agonists as potential new oral agents for the treatment of type 2 diabetes and obesity. Expert Opin Drug Discov. 2008;3:403–413.
  • Yang JW, Kim HS, Choi YW, et al. Therapeutic application of GPR119 ligands in metabolic disorders. Diabetes Obes Metab. 2018;20:257–269.
  • Cornall LM, Mathai ML, Hryciw DH, et al. Is GPR119 agonism an appropriate treatment modality for the safe amelioration of metabolic diseases? Expert Opin Investig Drugs. 2013;22:487–498.
  • Mo XL, Yang Z, Tao YX. Targeting GPR119 for the potential treatment of type 2 diabetes mellitus. Prog Mol Biol Transl Sci. 2014;121:95–131.
  • Jang YK, Lee KM, Jung KY, et al. Design, synthesis, and biological evaluation of aryl N-methoxyamide derivatives as GPR119 agonists. Bioorg Med Chem Lett. 2017;27:3909–3914.
  • Kato M, Furuie H, Kamiyama E, et al. Safety and pharmacokinetics of DS-8500a, a novel GPR119 agonist, after multiple oral doses in healthy Japanese males. Clin Drug Investig. 2018;38:519–525.
  • Han T, Lee BM, Park YH, et al. YH18968, a novel 1,2,4-triazolone G-protein coupled receptor 119 agonist for the treatment of type 2 diabetes mellitus. Biomol Ther (Seoul). 2018;26:201–209.
  • Wacker DA, Wang Y, Broekema M, et al. Discovery of 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (BMS-903452), an antidiabetic clinical candidate targeting GPR119. J Med Chem. 2014;57:7499–7508.
  • Spasov AA, Kosolapov VA, Babkov DA, et al. Effect of GRP119 receptor agonist, compound MBX-2982, on activity of human glucokinase. Bull Exp Biol Med. 2017;163:695–698.
  • Schwink L, Bossart M, Glombik H, et al. Pyrrolidinone derivatives as GPR119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders. WO2014056938. 2014.
  • Schwink L, Buning C, Glombik H, et al. Substituted indanone compounds as GPR119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders. WO2015150563. 2015.
  • Schwink L, Buning C, Glombik H, et al. Substituted fused heterocycles as GPR119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders. WO2015150564. 2015.
  • Schwink L, Buning C, Glombik H, et al. Isoindolinone compounds as GPR119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders. WO2015150565. 2015.
  • Schwink L, Buning C, Glombik H, et al. Azetidine compounds as GRP119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders. WO2018153849. 2018.
  • Schwink L, Buning C, Glombik H, et al. Azetidine compounds as GRP119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders. US20180237419. 2018.
  • Shintani Y, Niwa M, Monma S, et al. Substituted azole compounds, GPR119 agonists containing them, and their use as therapeutic agents for diabetes. WO2015170775. 2015.
  • Cow CN, Epple R, Nikulin V, et al. Preparation of piperidine derivatives as GPR119 modulators for treatment of diabetes, obesity, and related metabolic disorders. WO2014052619. 2014.
  • Han TD, Jung EH, Yi CH, et al. Novel triazolone derivatives or salts thereof as GPR119 activators and pharmaceutical composition comprising the same for diabetes treatment. WO2014175621. 2014.
  • Kim Y, Lee C, Choi D, et al. Pyrrolidinecarboxamide derivatives as GPR119 agonist and their preparation and use for the treatment of metabolic disorders. WO2015080446. 2015.
  • Yang J, Kim JW, Lee HK, et al. Piperazine derivative as GPR119 activator and method for the preparation thereof. WO2014077532. 2014.
  • Yang J, Kim JW, Lee K, et al. Cyclohexene derivative, preparation method thereof, and pharmaceutical composition for preventing or treating metabolic disease comprising the same as active ingredient. WO2017078352. 2017.
  • Qiu N, Chen JY, Yang T Phenyl pyrimidine derivative as GPR119 inhibitor for prevention and treatment of metabolic disorder and its preparation. CN106279041. 2017.
  • Ahn JH, Bae EJ, Lee IK, et al. Piperidine-aryl derivatives or pharmaceutically acceptable salt thereof, method for preparing same, and pharmaceutical composition containing same as active ingerdient. WO2018160024. 2018.
  • Chafeev M Compounds containing polysubstituted benzo[d][1,3]oxathiole, benzo[d][1,3]oxathiole 3-oxide or benzo[d][1,3]oxathiole 3,3-dioxide and uses thereof as agonists of G protein-coupled receptor 119. WO2019104418. 2019.
  • Lu MJ, Zhang HY, Wang GC Preparation of quinolinone derivatives and their application in the treatment of diabetes. CN104447693. 2016.
  • Yang Z, Fang Y, Liu R, et al. Preparation of fused pyrimidine derivatives useful as GPR119 agonists. CN110256461. 2020.
  • Yang Z, Fang Y, Jin Y, et al. Tetrahydropyridopyrimidine derivative, preparation and application. CN110256420. 2020.
  • Fang Y, Zhang S, Wu W, et al. Design and synthesis of tetrahydropyridopyrimidine derivatives as dual GPR119 and DPP-4 modulators. Bioorg Chem. 2020;94:103390.
  • Yang JS, Baek GM, Kim YJ, et al. Compounds having GPR119 agonistic activity, method for preparing the same, and pharmaceutical composition including the same as effective component. WO2016068453. 2016.
  • Cai ZY Preparation of halogenated benzenesulfonylhydrazines as GPR119 agonists. CN104592065. 2016.
  • Cai ZY Preparation of cyanophenylsulfonyl hydrazine structure containing compounds as GPR119 agonists for treatment of type II diabetes mellitus. CN104628612. 2016.
  • Cai ZY Preparation of alkyl substituted benzenesulfonyl hydrazides as GPR119 agonists. CN104610105. 2016.
  • Cai ZY. N-(4-(3-(4-Substituted-5,6,7,8-tetrahydronaphthalen-1-yl)ureido)phenyl) −2-(phenylsulfonyl)hydrazinecarboxamides as GPR119 agonists and their preparation method and application in preparation of medicines for treatment of type-II diabetes. CN104649937. 2015.
  • Cai ZY GPR119 agonist N-(4-(3-(4-chloro-5,6,7,8-tetrahydronaphthalen-1- yl)ureido)phenyl)-2-((methoxyphenyl)sulfonyl)hydrazinecarboxamide, its preparation method and application in preparation of medicines for treatment of type-II diabetes. CN104649944. 2016.
  • Yu B, Xie X, Zhang SY, et al. Preparation of Gordonoside F and derivatives for treating GPR119-mediated disease. CN103755762. 2014.
  • Zhang YY G protein coupled receptor agonist for treatment of diabetes. CN108117545. 2018.
  • Yang SQ, Wang Y, Liu LG, et al. Spiro ketal derivative, its preparation method and application in preparing the medical formulations as GPR119 agonist for treating diabetes. CN104592245. 2015.
  • Acton JJ, Edmondson SD, Liu P, et al. Substituted cyclopropyl compounds. WO2014052379. 2014.
  • Kelley DE, Liu P, Wood HB, et al. Methods of preventing or treating hypoglycemia by administering a GPR119 agonist. WO2017106112. 2017.
  • Liu P, Hu Z, DuBois BG, et al. Design of potent and orally active GPR119 agonists for the treatment of type II diabetes. ACS Med Chem Lett. 2015;6:936–941.
  • Hamiton J, Kotsikorou E. Parameterization of the GPR119 Receptor Agonist AR231453. J Comput Chem. 2018;39:35–41.
  • Kaushik AC, Kumar A, Rehman AU, et al. Deciphering G-protein-coupled receptor 119 agonists as promising strategy against type 2 diabetes using systems biology approach. ACS Omega. 2018;3:18214–18226.
  • Barba O, Bradley SE, Fyfe MCT, et al. Compounds for the treatment of metabolic disorders. WO2009034388. 2009.
  • Li G, Huan Y, Yuan B, et al. Discovery of novel xanthine compounds targeting DPP-IV and GPR119 as anti-diabetic agents. Eur J Med Chem. 2016;124:103–116.
  • Huan Y, Jiang Q, Li G, et al. The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo. Sci Rep. 2017;7:4351.
  • Li G, Meng B, Yuan B, et al. The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119. Eur J Med Chem. 2020;188:112017.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.