IP Library › Granted Patent US 12,624,024
Granted Patent B2
US 12,624,024 · App. 18/395,334 · Granted May 12, 2026

EP2 antagonist compounds

Inventors: Matthew Alexander James Duncton (San Bruno, CA); Vladimir V. Senatorov, Jr. (Oakland, CA); Aaron R. Friedman (Berkeley, CA); Steven Howard Olson (San Diego, CA)
Assignee: Reservoir Neuroscience, Inc.
C07D413/14C07D413/06C07D417/14C07D471/04C07D487/04
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Quick Facts
Patent No.
US 12,624,024
App. No.
18/395,334
Granted
May 12, 2026
Kind
B2
Abstract

Described herein are compounds of Formula (II): that are EP2 antagonists, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of diseases or conditions associated with EP2 activity.

Claims (51)

1 . A compound having the structure of Formula (II):

or a pharmaceutically acceptable salt thereof, wherein:

R 1 and R 2 are each independently hydrogen, deuterium, halogen, or C 1-4 alkyl;

R 3 and R 4 are each independently hydrogen, deuterium, halogen, or C 1-4 alkyl;

R 5 and R 6 are each independently hydrogen, deuterium, halogen, or C 1-4 alkyl; or R 5 and R 6 are taken together with the carbon atom to which they are attached to form an oxetane;

R 7 and R 8 are each independently hydrogen, deuterium, halogen, —CN, —C 1-4 alkyl, —C 1-4 haloalkyl, —OH, —O(C 1-4 alkyl), —O(C 1-4 haloalkyl), —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —(C 1-4 alkyl)O(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), —C(O)N(C 1-4 alkyl) 2 , substituted or unsubstituted C 3-6 cycloalkyl, or substituted or unsubstituted 3- to 6-membered heterocycloalkyl; or R 7 and R 8 are taken together with the carbon atom to which they are attached to form a cyclopropane or an oxetane;

R 9 and R 10 are each independently hydrogen, deuterium, halogen, or C 1-4 alkyl; or R 9 and R 10 are taken together with the carbon atom to which they are attached to form an oxetane;

R A1 is halogen, C 1-4 alkyl, or cyclopropyl; and

R A2 is hydrogen, deuterium, halogen, or optionally deuterated or halogenated methyl;

each R B is independently selected from the group consisting of halogen, —CN, —C 1-4 alkyl, —C 1-4 haloalkyl, —C 1-4 aminoalkyl, —C 1-4 hydroxyalkyl, —C 1-4 methoxyalkyl, —(C 1-4 alkyl)O(C 1-4 alkyl), —C(O)(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), —C(O)N(C 1-4 alkyl) 2 , —NH 2 , —NH(C 1-4 alkyl), —NH(C 3-6 cycloalkyl), —NH(C 3-6 heterocycloalkyl), —N(C 1-4 alkyl) 2 , —NHC(O)C 1-4 alkyl, —NHC(O)O(C 1-4 alkyl), —NHS(O) 2 C 1-4 alkyl, —OH, —O(C 1-4 alkyl), —O(C 1-4 haloalkyl), —SH, —S(C 1-4 alkyl), —S(O)(C 1-4 alkyl), —S(O)(NH)(C 1-4 alkyl), —S(O) 2 (C 1-4 alkyl), —S(O) 2 NH 2 , —S(O 2 )NHCH 3 , substituted or unsubstituted C 3-6 cycloalkyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl;

Ring C is bicyclic heterocycle having one or more nitrogen atoms; or Ring C is Ring C′;

each R C is independently selected from the group consisting of halogen, —CN, —C 1-4 alkyl, —C 1-4 haloalkyl, —(C 1-4 alkyl)O(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), —C(O)N(C 1-4 alkyl) 2 , —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —OH, —O(C 1-4 alkyl), —O(C 1-4 haloalkyl), —S(C 1-4 alkyl), —SO 2 C 1-4 alkyl, —SO 2 NHC 1-4 alkyl, substituted or unsubstituted C 3-6 cycloalkyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl; or two R C taken together form a carbonyl;

m is 0 to 3;

n is 1, 2 or 3; and

Ring C′ is selected from the group consisting of:

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R A1 is halogen.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R A1 is —Cl.

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

is selected from the group consisting of:

5 . The compound of claim 1 , having the structure:

or a pharmaceutically acceptable salt thereof.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the structure:

or a pharmaceutically acceptable salt thereof, wherein:

Ring C is bicyclic heterocycle having one or more nitrogen atoms; or Ring C is Ring C′;

each R C is independently selected from the group consisting of halogen, —CN, —C 1-4 alkyl, —C 1-4 haloalkyl, —(C 1-4 alkyl)O(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), —C(O)N(C 1-4 alkyl) 2 , —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —OH, —O(C 1-4 alkyl), —O(C 1-4 haloalkyl), —S(C 1-4 alkyl), —SO 2 C 1-4 alkyl, —SO 2 NHC 1-4 alkyl, substituted or unsubstituted C 3-6 cycloalkyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl; or two R C taken together form a carbonyl;

m is 0 to 3;

n is 1, 2 or 3; and

Ring C′ is selected from the group consisting of:

7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring C is bicyclic heteroaryl having one, two or three nitrogen atoms.

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring C is bicyclic heteroaryl consisting of a pyrrole ring or pyrazole ring fused to a phenyl ring, a pyridine ring, or a pyrimidine ring.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring C is a substituted or unsubstituted indole, or a substituted or unsubstituted azaindole.

10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring C is a substituted or unsubstituted indole.

11 . The compound of claim 1 , wherein Ring C is a bicyclic heterocycle having one or more nitrogens, selected from the group consisting of:

12 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R C is halogen, and m is 0, 1, or 2.

13 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring C is indole; Re is halogen, and m is 1.

14 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R B is independently halogen, C 1-4 alkyl, C 1-4 haloalkyl, —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), or —C(O)N(C 1-4 alkyl) 2 .

15 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R B is independently selected from the group consisting of —F, —Cl, —CN, —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , —OH, and —OCH 3 .

16 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

each R B is independently selected from the group consisting of —F, —Cl, —CN, —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , CH 2 NH 2 , —CH 2 NHBoc, —CH 2 OH, —CH 2 OCH 3 , —C(O)NH 2 , —C(O)NHCH 3 , —C(O)N(CH 3 ) 2 , —C(O)OH, —C(O)OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —NH(oxetanyl), —NHC(O)CH 3 , —NHS(O) 2 CH 3 , —OH, —OCH 3 , —OCH 2 CF 3 , —S(O)(NH)CH 3 , methylpyrazolyl, and pyrazolyl.

17 . The compound of claim 1 , having the structure:

or a pharmaceutically acceptable salt thereof.

18 . The compound of claim 1 , having the structure:

or a pharmaceutically acceptable salt thereof, or a tautomer thereof, wherein:

each R B is independently selected from the group consisting of halogen, —CN, —C 1-4 alkyl, —C 1-4 haloalkyl, —C 1-4 aminoalkyl, —C 1-4 hydroxyalkyl, —C 1-4 methoxyalkyl, —(C 1-4 alkyl)((C 1-4 alkyl), —C(O)(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), —C(O)N(C 1-4 alkyl) 2 , —NH 2 , —NH(C 1-4 alkyl), —NH(C 3-6 cycloalkyl), —NH(C 3-6 heterocycloalkyl), —N(C 1-4 alkyl) 2 , —NHC(O)C 1-4 alkyl, —NHC(O)O(C 1-4 alkyl), —NHS(O) 2 C 1-4 alkyl, —OH, —O(C 1-4 alkyl), —O(C 1-4 haloalkyl), —SH, —S(C 1-4 alkyl), —SO(C 1-4 alkyl), —S(O) 2 (C 1-4 alkyl), —S(O) 2 NH 2 , —S(O 2 )NHCH 3 , substituted or unsubstituted C 3-6 cycloalkyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl; and

each R C is independently selected from the group consisting of halogen, —CN, —C 1-4 alkyl, —C 1-4 haloalkyl, —(C 1-4 alkyl)O(C 1-4 alkyl), —C(O)OH, —C(O)O(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), —C(O)N(C 1-4 alkyl) 2 , —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —OH, —O(C 1-4 alkyl), —O(C 1-4 haloalkyl), —S(C 1-4 alkyl), —SO 2 C 1-4 alkyl, —SO 2 NHC 1-4 alkyl, substituted or unsubstituted C 3-6 cycloalkyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl; or two R C taken together form a carbonyl.

19 . The compound of claim 1 , wherein n is 1.

20 . The compound of claim 1 , wherein n is 2.

21 . The compound of claim 1 , wherein n is 3.

22 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, and at least one pharmaceutically acceptable excipient.

23 . A method of modulating the activity of the prostaglandin E2 receptor 2 (EP2) in a mammal comprising administering to the mammal a compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof.

24 . A method of treating a disease or condition that would benefit from the modulation of prostaglandin E2 receptor 2 (EP2) activity comprising administering to the mammal a compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 27, 2024
From: DUNCTON, MATTHEW ALEXANDER J.; SENATOROV, VLADIMIR V.; FRIEDMAN, AARON R.; OLSON, STEVEN HOWARD
To: RESERVOIR NEUROSCIENCE, INC.
Reel/Frame 068726/0994 →
Continuity (3)
Continuation PCTUS2022034901 · Jun 24, 2022
Provisional Application 63214645 · Jun 24, 2021
Related Publication 20240182459A1 · Jun 6, 2024
References Cited (67)
US 11241431B2 · Fretz et al. · 2022 [cited by applicant]
US 11325899B2 · Boss et al. · 2022 [cited by applicant]
US 11446298B2 · Boss et al. · 2022 [cited by applicant]
US 11712438B2 · Boss et al. · 2023 [cited by applicant]
US 11839613B2 · Boss et al. · 2023 [cited by applicant]
US 12011444B2 · Fretz et al. · 2024 [cited by applicant]
US 20200289517A1 · He · 2020 [cited by applicant]
US 20220048987A1 · Andreasson et al. · 2022 [cited by applicant]
US 20220175775A1 · Fretz et al. · 2022 [cited by applicant]
US 20220388955A1 · Watanabe et al. · 2022 [cited by applicant]
WO WO2008139287 · 2008 [cited by applicant]
WO WO2010052625 · 2010 [cited by applicant]
WO WO2020249527A1 · 2020 [cited by applicant]
B. Fox in “A Selective Prostaglandin E2 Receptor Subtype 2 (EP2) Antagonist Increases the Macrophage-Mediated Clearance of Amyloid-Beta Plaques” (J. Med. Chem. 2015, 58, 13, 5256-5273) (Year: 2015). [cited by examiner]
Af Forselles KJ, Root J, Clarke T, Davey D, Aughton K, Dack K, Pullen N. 2011. In vitro and in vivo characterization of PF-04418948, a novel, potent and selective prostaglandin EP [cited by applicant]
Alhallak K, Nagai J, Zaleski K, et al. Mast cells control lung type 2 inflammation via prostaglandin E2-driven soluble ST2. Immunity. 2024;57(6):1274-1288.e6. doi:10.1016/j.immuni.2024.05.003. [cited by applicant]
Amaradhi R, Banik A, Mohammed S, Patro V, Rojas A, Wang W, Motati DR, Dingledine R, Ganesh T. 2020. Potent, Selective, Water Soluble, Brain-Permeable EP2 Receptor Antagonist for Use in Central Nervous System Disease Mod… [cited by applicant]
Amaradhi R, Mohammed S, Banik A, Franklin R, Dingledine R, Ganesh T. 2022. Second-Generation Prostaglandin Receptor EP2 Antagonist, TG8-260, with High Potency, Selectivity, Oral Bioavailability, and Anti-Inflammatory Pr… [cited by applicant]
Aoki T, Frösen J, Fukuda M, Bando K, Shioi G, Tsuji K, Ollikainen E, Nozaki K, Laakkonen J, Narumiya S. 2017. Prostaglandin E2-EP2-NF-κB signaling in macrophages as a potential therapeutic target for intracranial aneury… [cited by applicant]
Arosh JA, Lee J, Balasubbramanian D, Stanley JA, Long CR, Meagher MW, Osteen KG, Bruner-Tran KL, Burghardt RC, Starzinski-Powitz A, Banu SK. 2015. Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as… [cited by applicant]
Banik A, Amaradhi R, Lee D, Sau M, Wang W, Dingledine R, Ganesh T. 2021. Prostaglandin EP2 receptor antagonist ameliorates neuroinflammation in a two-hit mouse model of Alzheimer's disease. J Neuroinflammation 18:273. d… [cited by applicant]
Birrell MA, Maher SA, Buckley J, Dale N, Bonvini S, Raemdonck K, Pullen N, Giembycz MA, Belvisi MG. 2013. Selectivity profiling of the novel EP2 receptor antagonist, PF-04418948, in functional bioassay systems: atypical… [cited by applicant]
Birrell MA, Nials AT. 2011. At last, a truly selective EP [cited by applicant]
Bonfill-Teixidor E, Otxoa-de-Amezaga A, Font-Nieves M, Sans-Fons MG, Planas AM. 2017. Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide. J Neuroinflammation 1… [cited by applicant]
Chen J, Deng JC, Zemans RL, et al. Age-induced prostaglandin E2 impairs mitochondrial fitness and increases mortality to influenza infection. Nat Commun. 2022;13(1):6759. Published Nov. 9, 2022. doi: 10.1038/s41467-022-… [cited by applicant]
Fang LZ, Linehan V, Licursi M, et al. Prostaglandin E2 activates melanin-concentrating hormone neurons to drive diet-induced obesity. Proc Natl Acad Sci U S A. 2023;120(31):e2302809120. doi:10.1073/pnas.2302809120. [cited by applicant]
Fox BM, Beck HP, Roveto PM, Kayser F, Cheng Q, Dou H, Williamson T, Treanor J, Liu H, Jin L, Xu G, Ma J, Wang S, Olson SH. 2015. A selective prostaglandin E2 receptor subtype 2 (EP2) antagonist increases the macrophage-… [cited by applicant]
Francica BJ, Holtz A, Lopez J, Freund D, Chen A, Wang D, Powell D, Kipper F, Panigrahy D, Dubois RN, Whiting CC, Prasit P, Dubensky TW. 2023. Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activat… [cited by applicant]
Ganesh T, Banik A, Dingledine R, Wang W, Amaradhi R. 2018. Peripherally Restricted, Highly Potent, Selective, Aqueous-Soluble EP2 Antagonist with Anti-Inflammatory Properties. Mol Pharm 15:5809-5817. doi:10.1021/acs.mol… [cited by applicant]
Ganesh T, Jiang J, Dingledine R. 2014a. Development of second generation EP2 antagonists with high selectivity. Eur J Med Chem 82:521-535, doi:10.1016/j.ejmech.2014.05.076. [cited by applicant]
Ganesh T, Jiang J, Shashidharamurthy R, Dingledine R. 2013. Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonists. ACS Med Chem Lett 4:616-621. doi:10.1021/ml400112h. [cited by applicant]
Ganesh T, Jiang J, Yang M-S, Dingledine R. 2014b. Lead optimization studies of cinnamic amide EP2 antagonists. J Med Chem 57:4173-4184. doi:10.1021/jm5000672. [cited by applicant]
Ganesh T. 2014. Prostanoid receptor EP2 as a therapeutic target. J Med Chem 57:4454-4465. doi:10.1021/jm401431x. [cited by applicant]
Ganesh T. 2023. Targeting EP2 Receptor for Drug Discovery: Strengths, Weaknesses, Opportunities, and Threats (SWOT) Analysis. J Med Chem 66:9313-9324. doi:10.1021/acs.jmedchem.3c00655. [cited by applicant]
Gill SK, Yao Y, Kay LJ, Bewley MA, Marriott HM, Peachell PT. 2016. The anti-inflammatory effects of PGE2 on human lung macrophages are mediated by the EP4 receptor. Br J Pharmacol 173:3099-3109. doi:10.1111/bph.13565. [cited by applicant]
Golden J, Illingworth L, Kavarian P, et al. EP2 Receptor Blockade Attenuates COX-2 Upregulation During Intestinal Inflammation. Shock. 2020;54(3):394-401. doi:10.1097/SHK.0000000000001444. [cited by applicant]
Jiang C, Amaradhi R, Ganesh T, Dingledine R. 2020. An Agonist Dependent Allosteric Antagonist of Prostaglandin EP2 Receptors. ACS Chem Neurosci 11:1436-1446. doi:10.1021/acschemneuro.0c00078. [cited by applicant]
Jiang J, Dingledine R. 2013. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection. Trends Pharmacol Sci 34:413-423. doi:10.1016/j.tips.2013.05.003. [cited by applicant]
Jiang J, Ganesh T, Du Y, Quan Y, Serrano G, Qui M, Speigel I, Rojas A, Lelutiu N, Dingledine R. 2012. Small molecule antagonist reveals seizure-induced mediation of neuronal injury by prostaglandin E2 receptor subtype E… [cited by applicant]
Jiang J, Quan Y, Ganesh T, Pouliot WA, Dudek FE, Dingledine R. 2013. Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation. Proc Natl Acad Sci U S A 1… [cited by applicant]
Jones VC, Birrell MA, Maher SA, Griffiths M, Grace M, O'Donnell VB, Clark SR, Belvisi MG. 2016. Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2. Br J Pharmacol 173:992-1004. doi:10… [cited by applicant]
Kameyama H, Dondapati P, Simmons R, et al. Needle biopsy accelerates pro-metastatic changes and systemic dissemination in breast cancer: Implications for mortality by surgery delay. Cell Rep Med. 2023;4(12):101330. doi:… [cited by applicant]
Kawahara K, Hohjoh H, Inazumi T, Tsuchiya S, Sugimoto Y. 2015. Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors. Biochim Biophys Acta 1851:414-421. doi:10.1016/j.bbalip.2014.07.008. [cited by applicant]
Kay LJ, Gilbert M, Pullen N, Skerratt S, Farrington J, Seward EP, Peachell PT. 2013. Characterization of the EP receptor subtype that mediates the inhibitory effects of prostaglandin E2 on IgE-dependent secretion from h… [cited by applicant]
Keery RJ, Lumley P. 1988. AH6809, a prostaglandin DP-receptor blocking drug on human platelets. Br J Pharmacol 94:745-754. doi:10.1111/j.1476-5381.1988.tb11584.x. [cited by applicant]
Li L, Yu Y, Hou R, Hao J, Jiang J. 2020. Inhibiting the PGE2 Receptor EP2 Mitigates Excitotoxicity and Ischemic Injury. ACS Pharmacol Transl Sci 3:635-643. doi:10.1021/acsptsci.0c00040. [cited by applicant]
Li P, Jiang H, Wu H, Wu D, Li H, Yu J, Lai J. 2018. AH6809 decreases production of inflammatory mediators by PGE2—EP2—CAMP signaling pathway in an experimentally induced pure cerebral concussion in rats. Brain Res 1698:… [cited by applicant]
Liu Q, Liang X, Wang Q, Wilson EN, Lam R, Wang J, Kong W, Tsai C, Pan T, Larkin PB, Shamloo M, Andreasson Kl. 2019. PGE2 signaling via the neuronal EP2 receptor increases injury in a model of cerebral ischemia. Proc Nat… [cited by applicant]
Makabe T, Koga K, Nagabukuro H, et al. Use of selective PGE2 receptor antagonists on human endometriotic stromal cells and peritoneal macrophages. Mol Hum Reprod. 2021;27(1):gaaa077. doi:10.1093/molehr/gaaa077. [cited by applicant]
Markoviď T, Jakopin Ž, Dolenc MS, Mlinarič-Raščan I. 2017. Structural features of subtype-selective EP receptor modulators. Drug Discov Today 22:57-71. doi:10.1016/j.drudis.2016.08.003. [cited by applicant]
Minhas PS, Latif-Hernandez A, McReynolds MR, Durairaj AS, Wang Q, Rubin A, Joshi AU, He JQ, Gauba E, Liu L, Wang C, Linde M, Sugiura Y, Moon PK, Majeti R, Suematsu M, Mochly-Rosen D, Weissman IL, Longo FM, Rabinowitz JD… [cited by applicant]
Nakamura N, Honjo M, Yamagishi R, Sakata R, Watanabe S, Aihara M. Synergic effects of EP2 and FP receptors co-activation on Blood-Retinal Barrier and Microglia. Exp Eye Res. 2023;237:109691. doi:10.1016/j.exer.2023.1096… [cited by applicant]
Morotti M, Grimm AJ, Hope HC, Arnaud M, Desbuisson M, Rayroux N, Barras D, Masid M, Murgues B, Chap BS, Ongaro M, Rota IA, Ronet C, Minasyan A, Chiffelle J, Lacher SB, Bobisse S, Murgues C, Ghisoni E, Ouchen K, Bou Mjah… [cited by applicant]
Perrot CY, Herrera JL, Fournier-Goss AE, Komatsu M. 2020. Prostaglandin E2 breaks down pericyte-endothelial cell interaction via EP1 and EP4-dependent downregulation of pericyte N-cadherin, connexin-43, and R-Ras. Sci R… [cited by applicant]
Rawat V, Banik A, Amaradhi R, Rojas A, Taval S, Nagy T, Dingledine R, Ganesh T. 2022. Pharmacological antagonism of EP2 receptor does not modify basal cardiovascular and respiratory function, blood cell counts, and bone… [cited by applicant]
Rojas A, Amaradhi R, Banik A, Jiang C, Abreu-Melon J, Wang S, Dingledine R, Ganesh T. 2021. A Novel Second-Generation EP2 Receptor Antagonist Reduces Neuroinflammation and Gliosis After Status Epilepticus in Rats. Neuro… [cited by applicant]
Rojas A, Ganesh T, Lelutiu N, Gueorguieva P, Dingledine R. 2015. Inhibition of the prostaglandin EP2 receptor is neuroprotective and accelerates functional recovery in a rat model of organophosphorus induced status epil… [cited by applicant]
Rojas A, Ganesh T, Manji Z, O'neill T, Dingledine R. 2016. Inhibition of the prostaglandin E2 receptor EP2 prevents status epilepticus-induced deficits in the novel object recognition task in rats. Neuropharmacology 110… [cited by applicant]
Rojas A, Ganesh T, Wang W, Wang J, Dingledine R. 2020. A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition. Neurobiol Dis 133:104399. doi:10.1016/j.nbd.2019.02… [cited by applicant]
Säfholm J, Manson ML, Bood J, et al. Prostaglandin E2 inhibits mast cell-dependent bronchoconstriction in human small airways through the E prostanoid subtype 2 receptor. J Allergy Clin Immunol. 2015;136(5):1232-9.e1. d… [cited by applicant]
Sluter MN, Hou R, Li L, Yasmen N, Yu Y, Liu J, Jiang J. 2021. EP2 Antagonists (2011-2021): A Decade's Journey from Discovery to Therapeutics. J Med Chem 64:11816-11836. doi:10.1021/acs.jmedchem.1c00816. [cited by applicant]
Thumkeo D, Punyawatthananukool S, Prasongtanakij S, Matsuura R, Arima K, Nie H, Yamamoto R, Aoyama N, Hamaguchi H, Sugahara S, Takeda S, Charoensawan V, Tanaka A, Sakaguchi S, Narumiya S. 2022. PGE2-EP2/EP4 signaling el… [cited by applicant]
Varvel NH, Amaradhi R, Espinosa-Garcia C, Duddy S, Franklin R, Banik A, Alemán-Ruiz C, Blackmar-Raynolds L, Wang W, Honore T, Ganesh T, Dingledine R. 2022. Preclinical development of an EP2 antagonist for post-seizure c… [cited by applicant]
Wang J, Zhi Z, Ding J, et al. Suppression of PGE2/EP2 signaling alleviates Hirschsprung disease by upregulating p38 mitogen-activated protein kinase activity. J Mol Med (Berl). 2023;101(9):1125-1139. doi:10.1007/s00109-… [cited by applicant]
Woodward DF, Pepperl DJ, Burkey TH, Regan JW. 1995. 6-Isopropoxy-9-oxoxanthene-2-carboxylic acid (AH 6809), a human EP2 receptor antagonist. Biochem Pharmacol 50:1731-1733. doi:10.1016/0006-2952(95)02035-7. [cited by applicant]
Zasłona Z, Pålsson-McDermott EM, Menon D, et al. The Induction of Pro-IL-1β by Lipopolysaccharide Requires Endogenous Prostaglandin E2 Production. J Immunol. 2017;198(9):3558-3564. doi:10.4049/jimmunol.1602072. [cited by applicant]
PUBCHEM, Substance Record for SID 318473298, Modify Date Nov. 30, 2016. [cited by applicant]