E-6123

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 526943

CAS#: 131614-02-3

Description: E-6123 is a platelet activating factor inhibitor potentially for the treatment of asthma. E6123 inhibited PAF inhalation-induced bronchoconstriction in guinea pigs with an ED50 value (p.o.) of 1.3 micrograms/kg which was lower than those of other PAF-antagonists such as WEB2347 (ED50 = 26 micrograms/kg) and Y-24180 (ED50 = 12 micrograms/kg). E6123 significantly inhibited PAF inhalation-induced eosinophil infiltration into the bronchiole and trachea, and bronchial hyperreactivity in guinea pigs after oral administration at 1 and 10 micrograms/kg, respectively. E6123 inhibited the PAF-induced increase in intracellular free calcium ion concentration ([Ca2+]i) in guinea pig eosinophils with an IC50 value of 14 nM.


Price and Availability

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E-6123 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 526943
Name: E-6123
CAS#: 131614-02-3
Chemical Formula: C23H22ClN5OS
Exact Mass: 451.1234
Molecular Weight: 451.973
Elemental Analysis: C, 61.12; H, 4.91; Cl, 7.84; N, 15.50; O, 3.54; S, 7.09


Synonym: E-6123; E 6123; E6123.

IUPAC/Chemical Name: (S)-(6-(2-chlorophenyl)-1,4-dimethyl-7,10-dihydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-9(8H)-yl)(cyclopropyl)methanone

InChi Key: JEQVYSUCZLYBRQ-LBPRGKRZSA-N

InChi Code: InChI=1S/C23H22ClN5OS/c1-12-21-27-26-13(2)29(21)23-19(20(25-12)15-5-3-4-6-17(15)24)16-9-10-28(11-18(16)31-23)22(30)14-7-8-14/h3-6,12,14H,7-11H2,1-2H3/t12-/m0/s1

SMILES Code: O=C(N(C1)CCC2=C1SC3=C2C(C4=CC=CC=C4Cl)=N[C@@H](C)C5=NN=C(C)N53)C6CC6


Technical Data

Appearance:
Solid powder

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

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).

Harmonized System Code:
293490


References

1: Gundemir S, Johnson GV. Intracellular localization and conformational state of transglutaminase 2: implications for cell death. PLoS One. 2009 Jul 1;4(7):e6123. doi: 10.1371/journal.pone.0006123. PubMed PMID: 19568436; PubMed Central PMCID: PMC2701606.

2: Tsuyuki K, Ichinowatari G, Tanimoto A, Yamada M, Yaginuma H, Ohuchi K. Possible participation of intracellular platelet-activating factor in NF-kappaB activation in rat peritoneal macrophages. Biochim Biophys Acta. 2002 Jun 13;1583(1):26-34. PubMed PMID: 12069846.

3: Ichinowatari G, Yamada M, Yaginuma H, Tsuyuki K, Tanimoto A, Ohuchi K. Participation of prostaglandin E2 and platelet-activating factor in thapsigargin-induced production of interleukin-6. Eur J Pharmacol. 2002 Jan 11;434(3):187-96. PubMed PMID: 11779582.

4: Kimura I, Sakamoto Y, Shibasaki M, Kobayashi Y, Matsuo H. Release of endothelins and platelet-activating factor by a rat pleural mesothelial cell line. Eur Respir J. 2000 Jan;15(1):170-6. PubMed PMID: 10678641.

5: Fujimura M, Ishiura Y, Amemiya T, Myou S, Matsuda T. No involvement of lipid mediators in a guinea pig model of ultrasonically nebulized distilled water-induced bronchoconstriction. Prostaglandins Other Lipid Mediat. 2000 Jan;60(1-3):49-58. PubMed PMID: 10680775.

6: Miike S, Kurasawa K, Saito Y, Iwamoto I. Platelet-activating factor activates mitogen-activated protein kinases through the activation of phosphatidylinositol 3-kinase and tyrosine kinase in human eosinophils. J Leukoc Biol. 2000 Jan;67(1):117-26. PubMed PMID: 10648006.

7: Yamada M, Tanimoto A, Ichinowatari G, Yaginuma H, Ohuchi K. Possible participation of intracellular platelet-activating factor in tumor necrosis factor-alpha production by rat peritoneal macrophages. Eur J Pharmacol. 1999 Jun 25;374(3):341-50. PubMed PMID: 10422778.

8: Yamada M, Ichinowatari G, Tanimoto A, Yaginuma H, Ohuchi K. Inhibition of tumor necrosis factor-alpha production by SK&F 98625, a CoA-independent transacylase inhibitor, in cultured rat peritoneal macrophages. Life Sci. 1998;62(20):PL 297-302. PubMed PMID: 9600332.

9: Kusano K, Seko T, Tanaka S, Shikata Y, Ando T, Ida S, Hosokawa M, Satoh T, Yuzuriha T, Horie T. Purification and characterization of rhesus monkey liver amido hydrolases and their roles in the metabolic polymorphism for E6123, a platelet-activating factor receptor antagonist. Drug Metab Dispos. 1996 Nov;24(11):1186-91. PubMed PMID: 8937851.

10: Fujimura M, Tsujiura M, Songür N, Myou S, Matsuda T. Involvement of PAF in postallergic propranolol-induced bronchoconstriction in guinea-pigs. Eur Respir J. 1996 Oct;9(10):2064-9. PubMed PMID: 8902468.

11: Sano H, Nakagawa N, Nakajima H, Yoshida S, Iwamoto I. Role of vascular cell adhesion molecule-1 and platelet-activating factor in selective eosinophil migration across vascular endothelial cells. Int Arch Allergy Immunol. 1995 Aug;107(4):533-40. PubMed PMID: 7542515.

12: Kaneko T, Ikeda H, Fu L, Nishiyama H, Okubo T. Platelet-activating factor mediates the ozone-induced increase in airway microvascular leakage in guinea pigs. Eur J Pharmacol. 1995 Mar 16;292(3-4):251-5. PubMed PMID: 7796863.

13: Kusano K, Tadano K, Tanaka S, Kagei Y, Ueda M, Miyazawa S, Abe Y, Ida S, Yuzuriha T. Development of radioimmunoassay for the novel platelet activating factor receptor antagonist, E6123, and its application to pharmacokinetics in laboratory animals. Biol Pharm Bull. 1994 Feb;17(2):334-9. PubMed PMID: 8205134.

14: Kusano K, Tanaka S, Ando T, Abe Y, Ida S, Yuzuriha T. Metabolic polymorphism of E6123 in rhesus monkey. Xenobiotica. 1993 Jun;23(6):599-608. PubMed PMID: 8212734.

15: Kusano K, Tanaka S, Abe Y, Ida S, Yuzuriha T. Pharmacokinetics of a new thienodiazepine platelet activating factor receptor antagonist (E6123) in laboratory animals. Is there a metabolic polymorphism in the rhesus monkey? Xenobiotica. 1993 Jun;23(6):589-98. PubMed PMID: 8212733.

16: Miyazawa S, Okano K, Kawahara T, Machida Y, Yamatsu I. Hapten synthesis for (+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tet rahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] triazolo[4,3-a][1,4]diazepine (E6123). Chem Pharm Bull (Tokyo). 1992 Mar;40(3):762-5. PubMed PMID: 1611690.

17: Miyazawa S, Okano K, Shimomura N, Clark RS, Kawahara T, Asano O, Yoshimura H, Miyamoto M, Sakuma Y, Muramoto K, et al. Structure-activity studies on triazolothienodiazepine derivatives as platelet-activating factor antagonists. Chem Pharm Bull (Tokyo). 1991 Dec;39(12):3215-20. PubMed PMID: 1814614.

18: Sakuma Y, Muramoto K, Harada K, Katayama S, Tsunoda H, Katayama K. Inhibitory effects of a novel PAF antagonist E6123 on anaphylactic responses in passively and actively sensitized guinea pigs and passively sensitized mice. Prostaglandins. 1991 Dec;42(6):541-55. PubMed PMID: 1801063.

19: Sakuma Y, Tsunoda H, Shirato M, Katayama S, Yamatsu I, Katayama K. Pharmacological effects of oral E6123, a novel PAF antagonist, on biological changes induced by PAF inhalation in guinea pigs. Prostaglandins. 1991 Nov;42(5):463-72. PubMed PMID: 1763202.

20: Sakuma Y, Tsunoda H, Katayama S, Harada K, Obaishi H, Shirato M, Yamada K, Miyazawa S, Okano K, Machida Y, et al. Effects of a novel PAF antagonist, E6123, on passive anaphylaxis. Agents Actions Suppl. 1990;31:255-8. PubMed PMID: 2080758.