IP Library › Granted Patent US 12,600,709
Granted Patent B2
US 12,600,709 · App. 18/822,733 · Granted Apr 14, 2026

Nonpeptide somatostatin type 5 receptor agonists and uses thereof

Inventors: Jian Zhao (San Diego, CA); Yunfei Zhu (San Diego, CA); Shimiao Wang (San Diego, CA); Mi Chen (San Diego, CA); Joseph Pontillo (San Diego, CA)
Assignee: CRINETICS PHARMACEUTICALS, INC.
C07D401/04A61P3/10C07D401/14
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Quick Facts
Patent No.
US 12,600,709
App. No.
18/822,733
Granted
Apr 14, 2026
Kind
B2
Abstract

Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.

Claims (4)

1 . A method of treating hyperinsulinism in a mammal, the method comprising administering a compound to the mammal in need thereof, wherein the compound is 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1, 1-trifluoropropan-2-yl] pyridine-3-carboxamide, or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein the compound is 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl] pyridine-3-carboxamide.

3 . The method of claim 1 , wherein the compound is a pharmaceutically acceptable salt of 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl] pyridine-3-carboxamide.

4 . The method of claim 1 , wherein the hyperinsulinism is congenital hyperinsulinism or drug induced hyperinsulinism.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 4, 2024
From: ZHAO, JIAN; ZHU, YUNFEI; WANG, SHIMIAO; CHEN, MI; PONTILLO, JOSEPH
To: CRINETICS PHARMACEUTICALS, INC.
Reel/Frame 068805/0821 →
Continuity (7)
Continuation 18612585 · Mar 21, 2024
Continuation 18484065 · Oct 10, 2023
Continuation 18190681 · Mar 27, 2023
Continuation 17930587 · Sep 8, 2022
Continuation 16989193 · Aug 10, 2020
Provisional Application 62886764 · Aug 14, 2019
Related Publication 20250136573A1 · May 1, 2025
References Cited (92)
US 6025372A · Yang et al. · 2000 [cited by applicant]
US 6127343A · Ankersen et al. · 2000 [cited by applicant]
US 7754744B2 · Binggeli et al. · 2010 [cited by applicant]
US 8110574B2 · Thurieau et al. · 2012 [cited by applicant]
US 8778925B2 · McDonald et al. · 2014 [cited by applicant]
US 9630976B2 · Ishida et al. · 2017 [cited by applicant]
US 9643951B2 · Ishida et al. · 2017 [cited by applicant]
US 10214540B2 · Ishida et al. · 2019 [cited by applicant]
US 10696689B2 · Han et al. · 2020 [cited by applicant]
US 11072598B2 · Han et al. · 2021 [cited by applicant]
US 11186590B2 · Han et al. · 2021 [cited by applicant]
US 11427567B2 · Ye et al. · 2022 [cited by applicant]
US 11479540B2 · Zhao et al. · 2022 [cited by applicant]
US 11608335B2 · Zhao et al. · 2023 [cited by applicant]
US 11773076B2 · Zhao et al. · 2023 [cited by applicant]
US 11834462B2 · Han et al. · 2023 [cited by applicant]
US 20060281764A1 · Gaul et al. · 2006 [cited by applicant]
US 20110059971A1 · Thurieau et al. · 2011 [cited by applicant]
US 20130040978A1 · Duffy et al. · 2013 [cited by applicant]
US 20150232478A1 · Ishida et al. · 2015 [cited by applicant]
US 20160311794A1 · Ishida et al. · 2016 [cited by applicant]
US 20200000816A1 · Ishida et al. · 2020 [cited by applicant]
US 20220048924A1 · Han et al. · 2022 [cited by applicant]
US 20220144802A1 · Zhao et al. · 2022 [cited by applicant]
US 20220323427A1 · Ferrara-Cook et al. · 2022 [cited by applicant]
US 20230143091A1 · Crowe et al. · 2023 [cited by applicant]
CA 2925651A1 · 2015 [cited by applicant]
EP 2871179A1 · 2015 [cited by applicant]
EP 3053916A1 · 2016 [cited by applicant]
EP 3053961A1 · 2016 [cited by applicant]
EP 3053916B1 · 2019 [cited by applicant]
EP 3581569A1 · 2019 [cited by applicant]
JP 2008543760A · 2008 [cited by applicant]
WO WO9845285A1 · 1998 [cited by applicant]
WO WO2005047253A1 · 2005 [cited by applicant]
WO WO2008051272A2 · 2008 [cited by applicant]
WO WO2009051705A1 · 2009 [cited by applicant]
WO WO2009158467A2 · 2009 [cited by applicant]
WO WO2010041054A1 · 2010 [cited by applicant]
WO WO2011027249A2 · 2011 [cited by applicant]
WO WO2011144891A1 · 2011 [cited by applicant]
WO WO2011146324A1 · 2011 [cited by applicant]
WO WO2014007228A1 · 2014 [cited by applicant]
WO WO2015046482A1 · 2015 [cited by applicant]
WO WO2018013676A1 · 2018 [cited by applicant]
WO WO2018147300A1 · 2018 [cited by applicant]
WO WO2018170284A1 · 2018 [cited by applicant]
WO WO2019023278A1 · 2019 [cited by applicant]
WO WO2019157458A1 · 2019 [cited by applicant]
WO WO2020061046A1 · 2020 [cited by applicant]
WO WO2020120697A1 · 2020 [cited by applicant]
WO WO2021030262A1 · 2021 [cited by applicant]
WO WO2022177974A1 · 2022 [cited by applicant]
WO WO2022177988A1 · 2022 [cited by applicant]
Abbott et al. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97:175-187 (1999). [cited by applicant]
Berge, Stephen M. et al. Pharmaceutical Salts. Journal of Pharmaceutical Sciences 66(1):1-19 (1977). [cited by applicant]
Brazeau, Paul et al. Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone. Science 179(4068):77-79 (1973). [cited by applicant]
Bundgaard, Hans. Chapter 5: Design and Application of Prodrugs. In: Textbook of Drug Design and Development :113-191 (1991). [cited by applicant]
Bundgaard, Hans. Means to Enhance Penetration: Prodrugs as a Means to Improve the Delivery of Peptide Drugs. Advanced Drug Delivery Review 8(1):1-38 (1992). [cited by applicant]
Corda et al. Treatment with long-acting lanreotide autogel in early infancy in patients with severe neonatal hyperinsulinism. Orphanet J Rare Dis. 12(1):108 (2017). [cited by applicant]
Crider. Somatostatin receptor agonists and antagonists. Expert Opinion on Therapeutic Patents 13(9):1427-1441 (2003). [cited by applicant]
De Cosio et al. Current and emerging agents for the treatment of hypoglycemia in patients with congenital hyperinsulinism. Paediatr Drugs 21(3):123-136 (2019). [cited by applicant]
De Leon et al. Congenital hypoglycemia disorders: new aspects of etiology, diagnosis, treatment and outcomes: highlights of the proceedings of the Congenital Hypoglycemia Disorders Symposium, Philadelphia Apr. 2016. Ped… [cited by applicant]
Esch, Fred et al. Primary Structure of Ovine Hypothalamic Somatostatin-28 and Somatostatin-25. Proceedings of the National Academy of Sciences of the United States of America 77(11):6827-6831 (1980). [cited by applicant]
Ferrara et al. Biomarkers of insulin for the diagnosis of hyperinsulinemic hypoglycemia in infants and children. J Pediatr 168:212-219 (2016). [cited by applicant]
Fowler et al. Discovery and Identification of Late Stage, Selective, Nonpeptide, Somatostatin Subtype 5 (Sst5) Agonists for the Treatment of Hyperinsulinemic Hypoglycemia. Poster #MON-089. Endo Online 2020. Jun. 8-22, 2… [cited by applicant]
Ishida et al. Discovery and SAR Studies of Orally Active Somatostatin Receptor Subtype-2 (SSTR2) Agonists for the Treatment of Acromegaly. ACS Chem Neurosci 11(10):1482-1494 (2020). [cited by applicant]
Khlebnikov et al. A Novel Strategy for the Synthesis of 3-(N-Heteryl)pyrrole Derivatives. Org Lett 14(14):3768-71 (2012). [cited by applicant]
Liu et al. Nonpeptide somatostatin agonists with sst4 selectivity: synthesis and structure-activity relationships of thioureas. J Med Chem 41(24):4693-705 (1998). [cited by applicant]
Lord et al. Hyperinsulinism in the neonate. Clin Perinatol. 45(1):61-74 (2018). [cited by applicant]
Mallinger et al. Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen. J Med Chem 58(4):1717-35 (2015). [cited by applicant]
Ortiz-Marciales et al. Catalytic enantioselective borane reduction of benzyl oximes: preparation of (S)-1-Pyridin-3-YL-Ethylamine BIS Hydrochloride. Organic Synth. 87:36-52 (2010). [cited by applicant]
Patel, Yogesh C, and Coimbatore B Srikant. Somatostatin Receptors. Trends in Endocrinology and Metabolism 8(10):398-405 (1997). [cited by applicant]
PCT/US2020/045610 International Search Report and Written Opinion dated Nov. 23, 2020. [cited by applicant]
Pradayrol, Lucien et al. N-Terminally Extended Somatostatin: The Primary Structure of Somatostatin-28. FEBS Letters 109(1):55-58 (1980). [cited by applicant]
Reisine, Terry, and Graeme I Bell. Molecular Biology of Somatostatin Receptors. Endocrine Reviews 16(4):427-442 (1995). [cited by applicant]
Rico-Bautista et al. Selective somatostatin 5 (SST5) and somatostatin 2 (SST2) nonpeptide agonists potently suppress glucose- and tolbutamide-stimulated dynamic insulin secretion from isolated human islets. Poster #8684… [cited by applicant]
Salomon-Estebanez et al. Conservatively treated congenital hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time. Orphanet J Rare Dis. 11(1):163 (2016). [cited by applicant]
Sanguinetti et al. hERG potassium channels and cardiac arrhythmia. Nature 440(7083):463-469 (2006). [cited by applicant]
Science IP Report. Chemical Structure Search (May 24, 2016) (311 pgs.). [cited by applicant]
Stanley. Perspective on the genetics and diagnosis of congenital hyperinsulinism disorders. J Clin Endocrinol Metab. 101(3):815-826 (2016). [cited by applicant]
Stella. Prodrugs: Some Thoughts and Current Issues. J Pharm Sci 99(12):4755-4765 (2010). [cited by applicant]
Sturchler et al. Selective Nonpeptide Somatostatin Receptor Subtype 5 (sst5) Agonists Suppress Glucose- and Sulfonylurea-induced Insulin Secretion in Rats. Poster. Endo 2019. Mar. 23-26, 2019; New Orleans. [cited by applicant]
Thornton et al. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr. 167(2):238-245 (2015). [cited by applicant]
Van Der Steen et al. A Multicenter experience with long-acting somatostatin analogues in patients with congenital hyperinsulinism. Horm Res Paediatr. 89(2):82-89 (2018). [cited by applicant]
Wang et al. The effect of global SSTR5 gene ablation on the endocrine pancreas and glucose regulation in aging mice. J Surg Res. 129(1):64-72 (2005). [cited by applicant]
Weckbecker et al. Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov 2(12):999-1017 (2003). [cited by applicant]
Widder, Kenneth J. et al. Method in Enzymology. Academic Press 112:309-396 (1985). [cited by applicant]
Wolf et al. Cytochrome P450 CYP2D6. IARC Sci Publ 148:209-229 (1999). [cited by applicant]
Wolkenberg et al. Design, synthesis, and evaluation of novel 3,6-diaryl-4-aminoalkoxyquinolines as selective agonists of somatostatin receptor subtype 2. J Med Chem 54:2351-2358 (2011). [cited by applicant]
Zhao et al. Discovery of nonpeptide 3,4-dihydroquinazoline-4-carboxamides as potent and selective sst2 agonists. Bioorg Med Chem Lett 30(17):127391 (2020). [cited by applicant]
Zhao et al. Discovery of substituted 3H-pyrido[2,3-d]pyrimidin-4-ones as potent, biased, and orally bioavailable sst2 agonist. Bioorg Med Chem Lett 30(21):127496 (2020). [cited by applicant]