98672-91-4

Basic information

• Product Name: SQ 29,548 (POTENT AND SPECIFIC THROMBOXA NE A2 RECEPT
• Synonyms: SQ 29,548 (POTENT AND SPECIFIC THROMBOXA NE A2 RECEPT;(Z)-7-[(1R,4S)-3α-[[2-[(Phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]heptan-2α-yl]-5-heptenoic acid;BMS-18290;1S-[1α,2β(5Z),3β,4α]]-7-[3-[2-(Phenylcarbamoyl)hydrazinomethyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid;RJNDVCNWVBWHLY-BHQIHCQQSA-N
• CAS NO: 98672-91-4
• Molecular Formula: C₂₁H₂₉N₃O₄
• Molecular Weight: 387.47266
• Mol File: 98672-91-4.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Density: 1.207g/cm³
• Refractive Index: 1.582
• Solubility: ≤0.9mg/ml in ethanol;5mg/ml in DMSO;0.14mg/ml in dimethyl formamide
• CAS DataBase Reference: SQ 29,548 (POTENT AND SPECIFIC THROMBOXA NE A2 RECEPT(CAS DataBase Reference)
• NIST Chemistry Reference: SQ 29,548 (POTENT AND SPECIFIC THROMBOXA NE A2 RECEPT(98672-91-4)
• EPA Substance Registry System: SQ 29,548 (POTENT AND SPECIFIC THROMBOXA NE A2 RECEPT(98672-91-4)

Safety Data

• Hazardous Substances Data: 98672-91-4(Hazardous Substances Data)

Usage

Description

SQ 29,548 is a highly selective TP receptor antagonist which binds to the human recombinant TP receptor with a Ki of 4.1 nM. It inhibits the aggregation of washed human platelets induced by U-46619 with an IC50 of 0.06 μM. It antagonizes U-46619 induced contraction of rat and guinea pig tracheal, arterial, and venous smooth muscles with drug/receptor dissociation constants (KB) in the range of 0.5-1.7 nM. SQ 29,548 also inhibits the contraction of rat vascular smooth muscle induced by 8-iso PGF2α.

in vitro

in guinea-pig trachea and rat aorta, sq 29,548 competitively antagonized the activity of 9,11-azo pgh2 with pa2 values of 7.8 and 8.4, respectively. sq 29,548 competitively antagonized contractions of guinea-pig tracheal spirals induced by 11,9-epoxymethano pgh2 with the pa2 value of 9.1. the sq 29,548 competitively antagonized tracheal induced by 11,9-epoxymethano pgh2 and pgd2 with the pa2 values of 8.2 and 8.3, respectively. sq 29,548 partially antagonized the contractions of guinea-pig tracheal spirals caused by pge2. sq 29,548 significantly inhibited the aorta contracting activity of 11,9-epoxymethano pgh2 (pa2 = 9.1) and thromboxane a2 released from perfused guinea-pig lungs upon arachidonic acid challenge [1].

in vivo

in anesthetized dogs, sq 29,548 (0.2 mg/kg/h) completely inhibited the vasoconstrictor response of the left circumflex coronary artery (lcx) caused by u-46619. sq 28,585 showed no effects on infarct size as compared with vehicle controls [3]. in sham mi rats, treatment with sq-29,548 significantly blunted this loss of ck activity and amino-nitrogen concentration from the ischemic myocardium. sq-29,548 significantly prevented the extension of ischemic damage in the myocardium and improved survival following acute coronary artery ligation [4].

references

[1] ogletree m l, harris d n, greenberg r, et al. pharmacological actions of sq 29,548, a novel selective thromboxane antagonist[j]. journal of pharmacology and experimental therapeutics, 1985, 234(2): 435-441.[2] abe t, takeuchi k, takahashi n, et al. rat kidney thromboxane receptor: molecular cloning, signal transduction, and intrarenal expression localization[j]. journal of clinical investigation, 1995, 96(2): 657.[3] grover g j, schumacher w a. effect of the thromboxane receptor antagonist sq 29,548 on myocardial infarct size in dogs[j]. journal of cardiovascular pharmacology, 1988, 11(1): 29-35.[4] hock c e, brezinski m e, lefer a m. anti-ischemic actions of a new thromboxane receptor antagonist, sq-29,548, in acute myocardial ischemia[j]. european journal of pharmacology, 1986, 122(2): 213-219.

InChI:InChI=1/C21H29N3O4/c25-20(26)11-7-2-1-6-10-16-17(19-13-12-18(16)28-19)14-22-24-21(27)23-15-8-4-3-5-9-15/h1,3-6,8-9,16-19,22H,2,7,10-14H2,(H,25,26)(H2,23,24,27)/b6-1-/t16-,17+,18-,19+/m1/s1

Upstream product

• 537-47-3 4-phenyl-semicarbazide 
• 128781-28-2 C₂₂H₂₉N₃O₄ 
• 104596-33-0 methyl <1α,2α(Z),3α,4α>-7-<3-formyl-7-oxabicyclo<2.2.1>hept-2-yl>-5-heptenoate 
• 128781-29-3 C₂₂H₃₁N₃O₄ 
• 128781-28-2 methyl <1S-<1α,2α(Z),3α,4α>>-7-<3-<<2-<(phenylamino)carbonyl>hydrazono>methyl>-7-oxabicyclo<2.2.1>hept-2-yl>-5-heptenoate 
• 94903-80-7 [1S-[1α,2α(5Z)3α,4α]]-7-[3-Formyl-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid, methyl ester 
• 128781-29-3 methyl <1S-<1α,2α(Z),3α,4α>>-7-<3-<<2-<(phenylamino)carbonyl>hydrazino>methyl>-7-oxabicyclo<2.2.1>hept-2-yl>-5-heptenoate 

Relevant articles and documents

7-Oxabicycloheptyl Carboxylic Acids as Thromboxane A2 Antagonists: Aza ω-Chain Analogues

A novel bicyclic prostaglandin analogue, >-7-acetyl>amino>methyl>-7-oxabicyclohept-2-yl>-5-heptenoic acid ((-)-7) was found to be a potent and selective thromboxane A2 (TxA2) receptor antagonist.Unlike the related series of ω-chain allylic alcohols, amide 7 and its congeners were uniformly free of direct contractile activity in vitro (bovine coronary) and in vivo (anesthetized guinea pig).Amide 7 was effective in the inhibition of (a) arachidonic acid induced platelet aggregation of human platelet-richplasma (I50 = 0.18 +/- 0.006 μM), (b) 11,9-epoxymethano-PGH2 induced platelet aggregation of human platelet-rich plasma (I50 = 0.24 μM), (c) 11,9-epoxymethano-PGH2 induced contraction of guinea pig trachea (Kb = 3.0 +/- 0.3 nM) or rat aorta (Kb = 8.8 +/- 1.1 nM), and (d) arachidonic acid induced bronchoconstriction in the anesthetized guinea pig (0.1-1.0 mg/kg iv).Amide 7 inhibited the binding of ->-7-hydrazino>methyl>-7-oxabicyclohept-2-yl>-5-heptenoic acid to human platelet membranes in a specific and saturable manner with a Kd = 49.6 +/- 1.4 nM.