Fructose-1,6-bisphosphatase Inhibitors: A Review of Recent (2000- 2017) Advances and Structure-Activity Relationship Studies

Author(s): Sarbjit Singh, Dipesh S. Harmalkar, Yongseok Choi*, Kyeong Lee*

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 29 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor


Diabetes mellitus, commonly referred to as diabetes, is the 8th leading cause of death worldwide. As of 2015, approximately 415 million people were estimated to be diabetic worldwide, type 2 diabetes being the most common accounting for approximately 90-95% of all diagnosed cases with increasing prevalence. Fructose-1,6-bisphosphatase is one of the important therapeutic targets recently discovered to treat this chronic disease. In this focused review, we have highlighted recent advances and structure-activity relationship studies in the discovery and development of different fructose-1,6-bisphosphatase inhibitors reported since the year 2000.

Keywords: Fructose-1, 6-bisphosphatase inhibitors, type 2 diabetes, adenosine 5’-monophosphate, hyperglycemia, diabetes mellitus, chronic disease.

WHO report on diabetes. Available at: [Access date: September 24, 2019].
Danaei, G.; Finucane, M.M.; Lu, Y.; Singh, G.M.; Cowan, M.J.; Paciorek, C.J.; Lin, J.K.; Farzadfar, F.; Khang, Y.H.; Stevens, G.A.; Rao, M.; Ali, M.K.; Riley, L.M.; Robinson, C.A.; Ezzati, M. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet, 2011, 378(9785), 31-40.
[] [PMID: 21705069]
WHO report on top 10 causes of mortality. Available at: [Access date: June , 2018].
Engelgau, M.M.; Narayan, K.M.V.; Herman, W.H. Screening for type 2 diabetes. Diabetes Care, 2000, 23(10), 1563-1580.
[] [PMID: 11023153]
Pilkis, S.J.; Granner, D.K. Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu. Rev. Physiol., 1992, 54, 885-909.
[] [PMID: 1562196]
Kaur, R.; Dahiya, L.; Kumar, M. Fructose-1,6-bisphosphatase inhibitors: a new valid approach for management of type 2 diabetes mellitus. Eur. J. Med. Chem., 2017, 141, 473-505.
[] [PMID: 29055870]
Dang, Q.; Van Poelje, P.D.; Erion, M.D. The discovery and development of MB07803, a second-generation fructose- 1,6-bisphosphatase inhibitor with im-proved pharmacokinetic properties, as a potential treatment of type 2 diabetes in: New therapeutic strategies for type 2 diabetes: small molecule approaches. In: The Royal Society of Chemistry; 11306-323., 2012; pp. 306-322.
Barciszewski, J.; Wisniewski, J.; Kolodziejczyk, R.; Jaskolski, M.; Rakus, D.; Dzugaj, A. T-to-R switch of muscle fructose-1,6-bisphosphatase involves fundamental changes of secondary and quaternary structure. Acta Crystallogr. D Struct. Biol., 2016, 72(Pt 4), 536-550.
[] [PMID: 27050133]
Van Schaftingen, E.; Jett, M.F.; Hue, L.; Hers, H.G. Control of liver 6-phosphofructokinase by fructose 2,6-bisphosphate and other effectors. Proc. Natl. Acad. Sci. USA, 1981, 78(6), 3483-3486.
[] [PMID: 6455662]
Pilkis, S.J.; El-Maghrabi, M.R.; Pilkis, J.; Claus, T. Inhibition of fructose-1,6-bisphosphatase by fructose 2,6-bisphosphate. J. Biol. Chem., 1981, 256(8), 3619-3622.
[PMID: 6260770]
Pilkis, S.J.; el-Maghrabi, M.R.; Claus, T.H. Hormonal regulation of hepatic gluconeogenesis and glycolysis. Annu. Rev. Biochem., 1988, 57, 755-783.
[] [PMID: 3052289]
Taketa, K.; Pogell, B.M. Allosteric inhibition of rat liver fructose 1,6-diphosphatase by adenosine 5′-monophosphate. J. Biol. Chem., 1965, 240, 651-662.
[PMID: 14275118]
Ke, H.M.; Liang, J-Y.; Zhang, Y.P.; Lipscomb, W.N. Conformational transition of fructose-1,6-bisphosphatase: structure comparison between the AMP complex (T form) and the fructose 6-phosphate complex (R form). Biochemistry, 1991, 30(18), 4412-4420.
[] [PMID: 1850623]
Zhang, Y.; Liang, J-Y.; Huang, S.; Lipscomb, W.N. Toward a mechanism for the allosteric transition of pig kidney fructose-1,6-bisphosphatase. J. Mol. Biol., 1994, 244(5), 609-624.
[] [PMID: 7990142]
Dang, Q.; Kasibhatla, S. R.; Reddy, K. R.; Erion, M. D.; Reddy, M. R.; Agarwal, A. Preparation of heteroaromatic phosphonates as fructose 1,6-bisphosphatase inhibitors. PCT Pat., WO 2000014095 A1 March 16, 2000.
Erion, M. D.; Vanpoelje, P. A. A combination of fructose- 1,6-bisphosphatase (FBPase) inhibitors and insulin sensitizers for the treatment of diabetes. PCT Pat., 2000. WO 2000038666 A2 20000706.
Bookser, B. C.; Dang, Q.; Reddy, K. R. Preparation of arylheterocycle phosphates as antidiabetics and aryl fructose-1,6-bisphosphatase inhibitors. Int. Patent Appl., WO2001066553, 2000.
Dang, Q.; Kasibhatla, S.R.; Reddy, K.R.; Erion, M.D.; Reddy, M.R.; Agarwal, A. Preparation of heteroaromatic phosphonates as fructose 1,6-bisphosphatase inhibitors. U.S. Patent US 6489476 B1, December 03, 2002.
Bauer, P.H.; Wright, S.W.; Schnur, R.C. Preparation of 4- phenylaminoquinazoline derivatives as fructose 1,6- bisphosphatase inhibitors. U.S. Patent US 20030144308 A1, July 31, 2007.
Yoshida, T.; Okuno, A. Fructose 1,6-bisphosphatase inhibitors as preventives for the onset of diabetes. PCT Patent WO 2004009118 A1, January 29, 2004.
Erion, M.D.; Van Poelje, P.D. Preparation of 2-(5- phosphono)furanyl substituted heteroar-omatic compounds as fructose-1,6- bisphosphatase (FBPase) inhibitors for use in combination with insulin sensitizers for the treatment of diabetes. US Patent, US 6756360 B1, June 29, 2004.
Yoshida, T.; Okuno, A. fructose 1,6-bisphosphatase (FBPase) inhibitor preventative agents for diabetes mellitus and related Conditions. US Patent, US 20050187194 A1, August 25, 2005.
Dang, Q.; Kopcho, J.J.; Hecker, S.J.; Ugarkar, B.G. Preparation of thiazole compounds as fructose 1,6- bisphosphatase inhibitors. PCT Patent, WO 2006023515 A2, March 2, 2006.
Carniato, D.; Arbellot, A.; Moinet, G.; Audet, A.; Botton, G. Preparation of imidazolylmethylbenzoates as fructose- 1,6-bisphosphatase inhibitors. Eur. Pat., EP 1752450 A1, February 14, 2007.
Gubler, M.; Haap, W.; Hebeisen, P.; Kitas, E.A.; Kuhn, B.; Minder, R.E.; Schott, B.; Wessel, H.P. Preparation of sulfonylureido thiazoles as fructose-1,6-bisphosphatase (FBPase) inhibitors for the treatment of diabetes. PCT Patent, WO 2007137962 A1, December 06, 2007.
Reddy, R. K.; Erion, M. D.; Dang, Q. Preparation of azabenzimidazole derivatives as prodrug inhibitors of fructose 1,6-bisphosphatase. PCT Patent, WO 2008019309 A, February 14, 2008.
Botton, G.; Leriche, C.; Arbellot, A.; Audet, A.; Gleitz, J. Preparation of 1H-benzimidazol-5-yl-3,6-dihydro-2H-1,3,4- thiadiazin-2-one derivatives as inhibitors of fructose-1,6- bisphosphatase, and their pharmaceutical compositions for treating diseases associated with insulin resistance syndrome especially diabetes. PCT Patent, WO 2009062576 A2, May 22, 2009.
Haap, W.; Hebeisen, P.; Kitas, E.A.; Kuhn, B.; Mohr, P.; Wessel, H.P. Preparation of pyridine compounds as fructose- 1,6-bisphosphatase inhibitors for use in treating diseases such as diabetes. PCT Patent, WO 2009068468 A2, June 04, 2009.
Hebeisen, P.; Kitas, E.A.; Minder, R.E.; Mohr, P.; Wessel, H.P. Preparation of aminothiazole derivatives as fructose- 1,6-bisphosphatase inhibitors for treating diseases such as diabetes. PCT Patent, WO 2009068467 A1, June 04, 2009.
Kantrowitz, E.R.; Heng, S. Dibenzofuran derivatives as fructose 1,6-biphosphatase inhibitors and their preparation and use in mono and combina-tion therapy of type 2 diabetes. PCT Patent, WO 2010091185 A2. August 12, 2010.
Li, J.; Tang, J.; Li, J.; He, H.; Gao, L.; Yang, F.; Yang, L.; Yusupu, A. Preparation of 2,5-diaryl-1,3,4-oxadiazole compounds for treating type II diabetes. China Patent, CN 102924399 A, February 13, 2013.
Wan, J.; Han, X.; Chen, H.; Zhu, H.; Feng, L.; Ren, Y.; Chi, B. Application of nitrostyrene derivatives for inhibiting fruc-tose-1,6-bisphosphatase. China Pat., CN 104146989 A, November 19, 2014.
Heng, S.; Harris, K.M.; Kantrowitz, E.R. Designing inhibitors against fructose 1,6-bisphosphatase: exploring natural products for novel inhibitor scaffolds. Eur. J. Med. Chem., 2010, 45(4), 1478-1484.
[] [PMID: 20116906]
Soberón, M.; Lopez, O.; Miranda, J.; Tabche, M.L.; Morera, C. Genetic evidence for 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) as a negative effector of cytochrome terminal oxidase cbb3 production in Rhizobium etli. Mol. Gen. Genet., 1997, 254(6), 665-673.
[] [PMID: 9202382]
Dougherty, M.J.; Boyd, J.M.; Downs, D.M. Inhibition of fructose-1,6-bisphosphatase by aminoimidazole carboxamide ribotide prevents growth of Salmonella enterica purH mutants on glycerol. J. Biol. Chem., 2006, 281(45), 33892-33899.
[] [PMID: 16987812]
Wright, S.W.; Hageman, D.L.; McClure, L.D.; Carlo, A.A.; Treadway, J.L.; Mathiowetz, A.M.; Withka, J.M.; Bauer, P.H. Allosteric inhibition of fructose-1,6-bisphosphatase by anilinoquinazolines. Bioorg. Med. Chem. Lett., 2001, 11(1), 17-21.
[] [PMID: 11140724]
Wright, S.W.; Carlo, A.A.; Danley, D.E.; Hageman, D.L.; Karam, G.A.; Mansour, M.N.; McClure, L.D.; Pandit, J.; Schulte, G.K.; Treadway, J.L.; Wang, I.K.; Bauer, P.H. 3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site. Bioorg. Med. Chem. Lett., 2003, 13(12), 2055-2058.
[] [PMID: 12781194]
von Geldern, T.W.; Lai, C.; Gum, R.J.; Daly, M.; Sun, C.; Fry, E.H.; Abad-Zapatero, C. Benzoxazole benzenesulfonamides are novel allosteric inhibitors of fructose-1,6-bisphosphatase with a distinct binding mode. Bioorg. Med. Chem. Lett., 2006, 16(7), 1811-1815.
[] [PMID: 16442285]
Zhu, D.W.; Xu, G.J.; Rehse, P.H.; Shi, R.; Zhao, F.K.; Lin, S.X. Crystallization and preliminary crystallographic data of fructose-1,6-bisphosphatase from human muscle. Acta Crystallogr. D Biol. Crystallogr., 2001, 57(Pt 6), 847-849.
[] [PMID: 11375504]
Lai, C.; Gum, R.J.; Daly, M.; Fry, E.H.; Hutchins, C.; Abad-Zapatero, C.; von Geldern, T.W. Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg. Med. Chem. Lett., 2006, 16(7), 1807-1810.
[] [PMID: 16446092]
Reddy, M.R.; Erion, M.D. Relative binding affinities of fructose-1,6-bisphosphatase inhibitors calculated using a quantum mechanics-based free energy perturbation method. J. Am. Chem. Soc., 2007, 129(30), 9296-9297.
[] [PMID: 17616196]
Erion, M.D.; Dang, Q.; Reddy, M.R.; Kasibhatla, S.R.; Huang, J.; Lipscomb, W.N.; van Poelje, P.D. Structure-guided design of AMP mimics that inhibit fructose-1,6-bisphosphatase with high affinity and specificity. J. Am. Chem. Soc., 2007, 129(50), 15480-15490.
[] [PMID: 18041833]
Dang, Q.; Kasibhatla, S.R.; Reddy, K.R.; Jiang, T.; Reddy, M.R.; Potter, S.C.; Fujitaki, J.M.; van Poelje, P.D.; Huang, J.; Lipscomb, W.N.; Erion, M.D. Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a series of orally-bioavailable phosphoramidase-sensitive prodrugs for the treatment of type 2 diabetes. J. Am. Chem. Soc., 2007, 129(50), 15491-15502.
[] [PMID: 18041834]
Erion, M.D.; van Poelje, P.D.; Dang, Q.; Kasibhatla, S.R.; Potter, S.C.; Reddy, M.R.; Reddy, K.R.; Jiang, T.; Lipscomb, W.N. MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes. Proc. Natl. Acad. Sci. USA, 2005, 102(22), 7970-7975.
[] [PMID: 15911772]
van Poelje, P.D.; Potter, S.C.; Chandramouli, V.C.; Landau, B.R.; Dang, Q.; Erion, M.D. Inhibition of fructose 1,6-bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in Zucker diabetic fatty rats. Diabetes, 2006, 55(6), 1747-1754.
[] [PMID: 16731838]
Dang, Q.; Kasibhatla, S.R.; Jiang, T.; Fan, K.; Liu, Y.; Taplin, F.; Schulz, W.; Cashion, D.K.; Reddy, K.R.; van Poelje, P.D.; Fujitaki, J.M.; Potter, S.C.; Erion, M.D. Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors. J. Med. Chem., 2008, 51(14), 4331-4339.
[] [PMID: 18570362]
Magnusson, I.; Rothman, D.L.; Katz, L.D.; Shulman, R.G.; Shulman, G.I. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J. Clin. Invest., 1992, 90(4), 1323-1327.
[] [PMID: 1401068]
Yoshida, T.; Okuno, A.; Izumi, M.; Takahashi, K.; Hagisawa, Y.; Ohsumi, J.; Fujiwara, T. CS-917, a fructose 1,6-bisphosphatase inhibitor, improves postprandial hyperglycemia after meal loading in non-obese type 2 diabetic Goto-Kakizaki rats. Eur. J. Pharmacol., 2008, 601(1-3), 192-197.
[] [PMID: 19014931]
Török, B.; Abid, M.; London, G.; Esquibel, J.; Török, M.; Mhadgut, S.C.; Yan, P.; Prakash, G.K.S. Highly enantioselective organocatalytic hydroxyalkylation of indoles with ethyl trifluoropyruvate. Angew. Chem. Int. Ed. Engl., 2005, 44(20), 3086-3089.
[] [PMID: 15844111]
Török, M.; Abid, M.; Mhadgut, S.C.; Török, B. Organofluorine inhibitors of amyloid fibrillogenesis. Biochemistry, 2006, 45(16), 5377-5383.
[] [PMID: 16618127]
Abid, M.; Teixeira, L.; Török, B. Triflic acid-catalyzed highly stereoselective friedel-crafts aminoalkylation of indoles and pyrroles. Org. Lett., 2008, 10(5), 933-935.
[] [PMID: 18254637]
Rudnitskaya, A.; Huynh, K.; Török, B.; Stieglitz, K. Novel heteroaromatic organofluorine inhibitors of fructose-1,6-bisphosphatase. J. Med. Chem., 2009, 52(3), 878-882.
[] [PMID: 19143528]
Hebeisen, P.; Kuhn, B.; Kohler, P.; Gubler, M.; Huber, W.; Kitas, E.; Schott, B.; Benz, J.; Joseph, C.; Ruf, A. Allosteric FBPase inhibitors gain 10(5) times in potency when simultaneously binding two neighboring AMP sites. Bioorg. Med. Chem. Lett., 2008, 18(16), 4708-4712.
[] [PMID: 18650089]
Dang, Q.; Brown, B.S.; Liu, Y.; Rydzewski, R.M.; Robinson, E.D.; van Poelje, P.D.; Reddy, M.R.; Erion, M.D. Fructose-1,6-bisphosphatase inhibitors. 1. Purine phosphonic acids as novel AMP mimics. J. Med. Chem., 2009, 52(9), 2880-2898.
[] [PMID: 19348494]
Tsukada, T.; Takahashi, M.; Takemoto, T.; Kanno, O.; Yamane, T.; Kawamura, S.; Nishi, T. Synthesis, SAR, and X-ray structure of tricyclic compounds as potent FBPase inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(20), 5909-5912.
[] [PMID: 19762234]
Tsukada, T.; Takahashi, M.; Takemoto, T.; Kanno, O.; Yamane, T.; Kawamura, S.; Nishi, T. Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(3), 1004-1007.
[] [PMID: 20045638]
Tsukada, T.; Kanno, O.; Yamane, T.; Tanaka, J.; Yoshida, T.; Okuno, A.; Shiiki, T.; Takahashi, M.; Nishi, T. Discovery of potent and orally active tricyclic-based FBPase inhibitors. Bioorg. Med. Chem., 2010, 18(14), 5346-5351.
[] [PMID: 20542703]
Heng, S.; Gryncel, K.R.; Kantrowitz, E.R. A library of novel allosteric inhibitors against fructose 1,6-bisphosphatase. Bioorg. Med. Chem., 2009, 17(11), 3916-3922.
[] [PMID: 19419876]
Dang, Q.; Reddy, K.R.; Kasibthatla, S.R.; Jiang, T.; Taplin, F.; Gibson, T.; Potter, S.C.; Poelje, P.D.; Reddy, M.R.; Erion, M.D. Discovery of Phosphonic acid-containing desaminobenzimidazoles as fructose 1,6-bisphosphatase inhibitors that are suitable for oral delivery via prodrugs. J. Diabetes Metab., 2010, 1, 105-108.
Dang, Q.; Kasibhatla, S.R.; Xiao, W.; Liu, Y.; Dare, J.; Taplin, F.; Reddy, K.R.; Scarlato, G.R.; Gibson, T.; van Poelje, P.D.; Potter, S.C.; Erion, M.D. Fructose-1,6-bisphosphatase Inhibitors. 2. Design, synthesis, and structure-activity relationship of a series of phosphonic acid containing benzimidazoles that function as 5′-adenosinemonophosphate (AMP) mimics. J. Med. Chem., 2010, 53(1), 441-451.
[] [PMID: 20055427]
Dang, Q.; Liu, Y.; Cashion, D.K.; Kasibhatla, S.R.; Jiang, T.; Taplin, F.; Jacintho, J.D.; Li, H.; Sun, Z.; Fan, Y.; DaRe, J.; Tian, F.; Li, W.; Gibson, T.; Lemus, R.; van Poelje, P.D.; Potter, S.C.; Erion, M.D. Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of fructose-1,6-bisphosphatase. J. Med. Chem., 2011, 54(1), 153-165.
[] [PMID: 21126019]
Triscari, J.; Walker, J.; Feins, K.; Tao, B.; Bruce, S.R. In multiple ascending dose of CS-917, a novel fructose 1,6-bisphosphatase (FBPase) Inhibitor, in subjects with type 2 diabetes treated for 14 days; American Diabetes Association: Alexandria, VA, 2006.
Dang, Q.; Kasibthatla, S.R.; Jiang, T.; Taplin, F.; Gibson, T.; Potter, S.C.; Poeljek, P.D.; Erion, M.D. Oxazole phosphonic acids as fructose 1,6-bisphosphatase inhibitors with potent glucose-lowering activity. MedChemComm, 2011, 2, 287-290.
Kitas, E.; Mohr, P.; Kuhn, B.; Hebeisen, P.; Wessel, H.P.; Haap, W.; Ruf, A.; Benz, J.; Joseph, C.; Huber, W.; Sanchez, R.A.; Paehler, A.; Benardeau, A.; Gubler, M.; Schott, B.; Tozzo, E. Sulfonylureido thiazoles as fructose-1,6-bisphosphatase inhibitors for the treatment of type-2 diabetes. Bioorg. Med. Chem. Lett., 2010, 20(2), 594-599.
[] [PMID: 19969452]
Hebeisen, P.; Haap, W.; Kuhn, B.; Mohr, P.; Wessel, H.P.; Zutter, U.; Kirchner, S.; Ruf, A.; Benz, J.; Joseph, C.; Alvarez-Sánchez, R.; Gubler, M.; Schott, B.; Benardeau, A.; Tozzo, E.; Kitas, E. Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase. Bioorg. Med. Chem. Lett., 2011, 21(11), 3237-3242.
[] [PMID: 21550236]
He, H.B.; Gao, L.X.; Zhou, Y.Y.; Liu, T.; Tang, J.; Gong, X.P.; Qiu, W.W.; Li, J.Y.; Li, J.; Yang, F. Design, synthesis and biological activity evaluation of 2,5-diphenyl-1,3,4-oxadiazole derivatives as novel inhibitors of fructose-1,6-bisphosphatase. Heterocycles, 2012, 85, 2693-2712.
Liao, B.R.; He, H.B.; Yang, L.L.; Gao, L.X.; Chang, L.; Tang, J.; Li, J.Y.; Li, J.; Yang, F. Synthesis and structure-activity relationship of non-phosphorus-based fructose-1,6-bisphosphatase inhibitors: 2,5-Diphenyl-1,3,4-oxadiazoles. Eur. J. Med. Chem., 2014, 83, 15-25.
[] [PMID: 24946215]
Bie, J.; Liu, S.; Zhou, J.; Xu, B.; Shen, Z. Design, synthesis and biological evaluation of 7-nitro-1H-indole-2-carboxylic acid derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg. Med. Chem., 2014, 22(6), 1850-1862.
[] [PMID: 24530031]
Bie, J.; Liu, S.; Li, Z.; Mu, Y.; Xu, B.; Shen, Z. Discovery of novel indole derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase. Eur. J. Med. Chem., 2015, 90, 394-405.
[] [PMID: 25461330]
Wright, S.W.; Carlo, A.A.; Carty, M.D.; Danley, D.E.; Hageman, D.L.; Karam, G.A.; Levy, C.B.; Mansour, M.N.; Mathiowetz, A.M.; McClure, L.D.; Nestor, N.B.; McPherson, R.K.; Pandit, J.; Pustilnik, L.R.; Schulte, G.K.; Soeller, W.C.; Treadway, J.L.; Wang, I.K.; Bauer, P.H. Anilinoquinazoline inhibitors of fructose 1,6-bisphosphatase bind at a novel allosteric site: synthesis, in vitro characterization, and X-ray crystallography. J. Med. Chem., 2002, 45(18), 3865-3877.
[] [PMID: 12190310]
Rosini, M.; Mancini, F.; Tarozzi, A.; Colizzi, F.; Andrisano, V.; Bolognesi, M.L.; Hrelia, P.; Melchiorre, C. Design, synthesis, and biological evaluation of substituted 2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamine related compounds as fructose-1,6-bisphosphatase inhibitors. Bioorg. Med. Chem., 2006, 14(23), 7846-7853.
[] [PMID: 16908175]
Choe, J.Y.; Nelson, S.W.; Arienti, K.L.; Axe, F.U.; Collins, T.L.; Jones, T.K.; Kimmich, R.D.A.; Newman, M.J.; Norvell, K.; Ripka, W.C.; Romano, S.J.; Short, K.M.; Slee, D.H.; Fromm, H.J.; Honzatko, R.B. Inhibition of fructose-1,6-bisphosphatase by a new class of allosteric effectors. J. Biol. Chem., 2003, 278(51), 51176-51183.
[] [PMID: 14530289]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 31 August, 2018
Page: [5542 - 5563]
Pages: 22
DOI: 10.2174/0929867325666180831133734
Price: $65

Article Metrics

PDF: 34
PRC: 1