Synonym
RO-1138452; RO1138452; RO 1138452; CAY10441; CAY-10441; CAY 10441;
IUPAC/Chemical Name
N-(4-(4-isopropoxybenzyl)phenyl)-4,5-dihydro-1H-imidazol-2-amine4,5-Dihydro-N-(4-((4-(1-methylethoxy)phenyl)methyl)phenyl)-1H-imadazol-2-amine
InChi Key
GYYRMJMXXLJZAB-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H23N3O/c1-14(2)23-18-9-5-16(6-10-18)13-15-3-7-17(8-4-15)22-19-20-11-12-21-19/h3-10,14H,11-13H2,1-2H3,(H2,20,21,22)
SMILES Code
CC(OC1=CC=C(C=C1)CC2=CC=C(NC3=NCCN3)C=C2)C
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, DMF, and ethanol
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
RO-1138452 is selective for the IP receptor over several prostaglandin E2 (PGE2) receptor subtypes and a panel of 30 other receptors and ion channels but does bind to the α2A-adrenergic and imidazoline I2 receptors. RO-1138452 inhibits carbaprostacyclin-induced cAMP accumulation in SH-SY5Y cells (pKB = 8.8) and vasorelaxation of isolated human pulmonary arteries induced by the IP receptor agonist cicaprost (pA2 = 8.2). It also decreases cicaprost-induced inhibition of platelet aggregation in human platelet-rich plasma. RO-1138452 reduces acetic acid-induced writhing and carrageenan-induced paw hyperalgesia in rats (ED50s = 4 and 2.8 mg/kg, respectively).
In vitro activity:
This study found that RO-1138452 is a potent and selective IP receptor antagonist that is an important, potential clinical agent in cases where prostacyclin has a pathophysiological function. RO-1138452 antagonized relaxation of human pulmonary artery, guinea-pig aorta and rabbit mesenteric artery induced by the selective IP agonist cicaprost.
Reference: Br J Pharmacol. 2006 Sep;149(1):110-20. https://pubmed.ncbi.nlm.nih.gov/16880763/
In vivo activity:
The increase in the retinal arteriolar diameter induced by intravitreal injection of NOR3 was not suppressed by RO-1138452. The dose of RO-1138452 injected intravitreally in the present study significantly reduced the increase in the retinal arteriolar diameter induced by prostaglandin I2 (PGI2). Male Wistar rats were used to examine the effects ofseveral compounds, including RO-1138452, on the changes in the retinal arteriolar diameter induced by intravitreal administration of NOR3.
Reference: Biomolecules. 2022 Oct 1;12(10):1403. https://pubmed.ncbi.nlm.nih.gov/36291611/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
30.0 |
96.96 |
| DMSO |
20.0 |
64.64 |
| Ethanol |
20.0 |
64.64 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
309.41
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Jones RL, Wise H, Clark R, Whiting RL, Bley KR. Investigation of the prostacyclin (IP) receptor antagonist RO1138452 on isolated blood vessel and platelet preparations. Br J Pharmacol. 2006 Sep;149(1):110-20. doi: 10.1038/sj.bjp.0706841. Epub 2006 Jul 31. PMID: 16880763; PMCID: PMC1629403.
2. Bley KR, Bhattacharya A, Daniels DV, Gever J, Jahangir A, O'Yang C, Smith S, Srinivasan D, Ford AP, Jett MF. RO1138452 and RO3244794: characterization of structurally distinct, potent and selective IP (prostacyclin) receptor antagonists. Br J Pharmacol. 2006 Feb;147(3):335-45. doi: 10.1038/sj.bjp.0706554. PMID: 16331286; PMCID: PMC1751302.
3. Mori A, Seki H, Mizukoshi S, Uezono T, Sakamoto K. Role of Prostaglandins in Nitric Oxide-Induced Glial Cell-Mediated Vasodilation in Rat Retina. Biomolecules. 2022 Oct 1;12(10):1403. doi: 10.3390/biom12101403. PMID: 36291611; PMCID: PMC9599243.
4. Misawa H, Ohashi W, Tomita K, Hattori K, Shimada Y, Hattori Y. Prostacyclin mimetics afford protection against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice. Toxicol Appl Pharmacol. 2017 Nov 1;334:55-65. doi: 10.1016/j.taap.2017.09.003. Epub 2017 Sep 5. PMID: 28887131.
In vitro protocol:
1. Jones RL, Wise H, Clark R, Whiting RL, Bley KR. Investigation of the prostacyclin (IP) receptor antagonist RO1138452 on isolated blood vessel and platelet preparations. Br J Pharmacol. 2006 Sep;149(1):110-20. doi: 10.1038/sj.bjp.0706841. Epub 2006 Jul 31. PMID: 16880763; PMCID: PMC1629403.
2. Bley KR, Bhattacharya A, Daniels DV, Gever J, Jahangir A, O'Yang C, Smith S, Srinivasan D, Ford AP, Jett MF. RO1138452 and RO3244794: characterization of structurally distinct, potent and selective IP (prostacyclin) receptor antagonists. Br J Pharmacol. 2006 Feb;147(3):335-45. doi: 10.1038/sj.bjp.0706554. PMID: 16331286; PMCID: PMC1751302.
In vivo protocol:
1. Mori A, Seki H, Mizukoshi S, Uezono T, Sakamoto K. Role of Prostaglandins in Nitric Oxide-Induced Glial Cell-Mediated Vasodilation in Rat Retina. Biomolecules. 2022 Oct 1;12(10):1403. doi: 10.3390/biom12101403. PMID: 36291611; PMCID: PMC9599243.
2. Misawa H, Ohashi W, Tomita K, Hattori K, Shimada Y, Hattori Y. Prostacyclin mimetics afford protection against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice. Toxicol Appl Pharmacol. 2017 Nov 1;334:55-65. doi: 10.1016/j.taap.2017.09.003. Epub 2017 Sep 5. PMID: 28887131.
1: Auberson YP, Briard E, Sykes D, Reilly J, Healy M. Ligand Specific Efficiency (LSE) Index for PET Tracer Optimization. ChemMedChem. 2016 Jul 5;11(13):1415-27. doi: 10.1002/cmdc.201600112. Epub 2016 May 19. PMID: 27193393.
2: Syed NI, Jones RL. Assessing the agonist profiles of the prostacyclin analogues treprostinil and naxaprostene, particularly their DP₁ activity. Prostaglandins Leukot Essent Fatty Acids. 2015 Apr;95:19-29. doi: 10.1016/j.plefa.2014.11.011. Epub 2014 Dec 5. PMID: 25542069.
3: McCormick C, Jones RL, Kennedy S, Wadsworth RM. Activation of prostanoid EP receptors by prostacyclin analogues in rabbit iliac artery: implications for anti-restenotic potential. Eur J Pharmacol. 2010 Sep 1;641(2-3):160-7. doi: 10.1016/j.ejphar.2010.04.035. Epub 2010 May 5. PMID: 20450909.
4: Clark RD, Jahangir A, Severance D, Salazar R, Chang T, Chang D, Jett MF, Smith S, Bley K. Discovery and SAR development of 2-(phenylamino) imidazolines as prostacyclin receptor antagonists [corrected]. Bioorg Med Chem Lett. 2004 Feb 23;14(4):1053-6. doi: 10.1016/j.bmcl.2003.10.070. Erratum in: Bioorg Med Chem Lett. 2004 May 17;14(10):2697. PMID: 15013022.
