3-dihydro-5-benzoyl-(+-)-1h-pyrrolizine-1-carboxylicaci
Ketorolac
CAS: 74103-06-3
Molecular Formula: C15H13NO3
3-dihydro-5-benzoyl-(+-)-1h-pyrrolizine-1-carboxylicaci - Names and Identifiers
3-dihydro-5-benzoyl-(+-)-1h-pyrrolizine-1-carboxylicaci - Physico-chemical Properties
| Molecular Formula | C15H13NO3 |
| Molar Mass | 255.27 |
| Density | 1.33±0.1 g/cm3(Predicted) |
| Melting Point | 160-161°C |
| Boling Point | 493.2±40.0 °C(Predicted) |
| Flash Point | 252.1°C |
| Water Solubility | 183mg/L(32 ºC) |
| Solubility | Chloroform (Slightly), Methanol (Slightly) |
| Vapor Presure | 1.52E-10mmHg at 25°C |
| Appearance | Solid |
| Color | Off-White |
| pKa | 3.49 ±0.02(at 25℃) |
| Storage Condition | 2-8°C |
| Refractive Index | 1.659 |
| Physical and Chemical Properties | Crystallized from ethyl acetate-diethyl ether, melting point 160-161 °c. UV maximum absorption (methanol):245,312m (n7080, 17400). pKa 3.49±0.02. Acute toxicity LD50 mice (mg/kg): about 200 oral. ()-configuration: crystallized from hexane-ethyl acetate, melting point 174 °c; Melting point 154 156 °c. [Α] D 173 °(C = 1, methanol). (-)-configuration: crystallized from hexane-ethyl acetate, melting point 169-170 °c; Melting point 153-155 °c. [Α] D-176 °(C = 1, methanol). Ketorolac Tromethamine:[74103-07-4]. Crystallized from ethyl acetate, melting point 169-170 °c. |
| Use | Used as an anti-inflammatory analgesic |
| In vitro study | (R, S)-,(S)-, and (R)-Ketorolac inhibit both COX isoforms in recombinant rat and human enzyme systems, and rat COX (rCOX) similar to human COX (hCOX) inhibitors. (R, S)-Ketorolac inhibits rat COX-1,COX-2, and human COX-1,COX-2, with IC50 of 0.27 μm, 2.06 μm, respectively, 1.23 μm and 3.50 μm. The Ketorolac(S) enantiomer is 2 times more effective than Racemate on rat COX-1, with an IC50 of 0.10 μm, while the (R)-enantiomer is inactive, IC50 > 100 μm. Ketorolac acts on HEL cells (COX-1) and LPS-s-stimulated Mono Mac 6 cells (COX-2) to inhibit the formation of eicosanoids with IC50 of 0.025 μm and 0.039 μm, respectively, but NO accumulation was also not inhibited by LPS-stimulated RAW 264.7 cell suspension at 300 μm. The effect of Ketorolac on human bone cells, 24 hours later, significantly inhibited the uptake of thorax, which was dose-dependent, and inhibited the proliferation of hOBs cells and the cell cycle was halted in the G0/G1 phase. |
| In vivo study | (R, S)-Ketorolac was significantly more effective than Indomethacin or Diclofenac in acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema in rats. The treatment of Ketorolac at a dose of ≥ 1 mg/kg significantly inhibited COX-1 activity and gastric PG synthesis by 95% and gastric PG synthesis by> 88%. Ketorolac at a dose of ≤ 3 mg/kg did not inhibit COX-2 activity, but at a dose of 10 and 30 mg/kg significantly inhibited COX-2 activity, inhibition was 75% and 91%, respectively. Ketorolac can cause damage to the stomach only when the dose reaches to inhibit COX-1 and COX-2 at the same time, or when combined with COX-2 inhibitors. |
3-dihydro-5-benzoyl-(+-)-1h-pyrrolizine-1-carboxylicaci - Risk and Safety
| UN IDs | 3249 |
| Hazard Class | 6.1(a) |
| Packing Group | II |
| Toxicity | LD50 orally in mice: ~200 mg/kg (Rooks) |
3-dihydro-5-benzoyl-(+-)-1h-pyrrolizine-1-carboxylicaci - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 0 ml | 0 ml | 0 ml |
| 5 mM | 0 ml | 0 ml | 0 ml |
| 10 mM | 0 ml | 0 ml | 0 ml |
| 5 mM | 0 ml | 0 ml | 0 ml |
Last Update：2024-01-02 23:10:35
3-dihydro-5-benzoyl-(+-)-1h-pyrrolizine-1-carboxylicaci - Reference Information
| EPA chemical substance information | information provided by: ofmpeb.epa.gov (external link) |
| pharmacological action | ketorolac, also known as tonglik, tongliqing, anseria, ketorolac tromethamine, it is a non-steroidal analgesic and anti-inflammatory drug. It is a derivative of pyrrolidine acid. Its chemical structure and pharmacological effects are similar to those of tolmetin, zomethacin and indomethacin. By inhibiting cyclooxygenase, the synthesis and release of prostaglandins are inhibited to produce an anti-inflammatory effect. It can reduce the heat induced Fever body temperature, and its inhibition of central nervous system prostaglandin synthesis, with strong analgesic and moderate anti-inflammatory antipyretic and inhibit platelet aggregation, and no inhibition of respiration and addiction. In animal experiments, its analgesic effect is stronger than aspirin, indomethacin and naproxen, and its anti-inflammatory effect is equal to or stronger than indomethacin, naproxen and phenylbutazone, naproxen was the same. It can inhibit the platelet aggregation induced by arachidonic acid and collagen, but does not inhibit the induction of adenosine diphosphate (ADP). This product is quickly and completely absorbed after intramuscular injection, almost completely absorbed after oral administration, food can slow down the absorption rate, but does not affect the degree of absorption, bioavailability of 80% ~ 100%. Intramuscular injection of 30mg is usually 10 minutes after the obvious pain, 50 minutes after the peak plasma concentration of 2.2 μg/mL, oral usually 30~60 minutes after the obvious pain, 1.5~4 hours plasma concentration peak, plasma half-life of young people about 5.3 hours, the elderly about 7 hours, analgesic effect can be maintained for 6 to 8 hours. 91.4% by the urinary tract discharge, the rest of the fecal discharge. Renal insufficiency, the total plasma clearance rate decreased, the elimination of prolonged half-life, it should reduce the dose. Clinical Application: ketorolac is mainly used for short-term treatment of various kinds of pain including postoperative pain (such as abdominal, chest, urology, gynecology, stomatology, orthopedic and other postoperative pain) and various causes of acute skeletal muscle pain, such as sprains, dislocation, fractures and soft tissue injuries, and other diseases caused by pain such as postpartum pain, acute renal colic, toothache, sciatica, late cancer pain, trauma pain, biliary colic, etc., can be used as a substitute for morphine, pethidine. |
| biological activity | Ketorolac is a non-selective COX inhibitor that acts on human COX-1 and COX-2, the IC50 values were 1.23 μm and 3.50 μm, respectively. |
| Target | Value |
| COX-1 (human) | 1.23 μM |
| COX-2 (human) | 3.50 μM |
| Use | Anti-inflammatory analgesic, and has anti-platelet aggregation effect. used as anti-inflammatory analgesic |
| production method | Method 1: 2-(methylthio) was obtained from pyrrole and dimethyl sulfide in the presence of N-chlorosuccinimide pyrrole. 2-(methylthio) pyrrole is acylated with benzoyldimethylamine in a solution of phosphorus oxychloride in dichloroethane under reflux to give 2-(methylthio)-5-benzoylpyrrole. The compound is condensed with spirodioxane Dione to give compound (I). Compound (I) is first oxidized and then subjected to methanolysis to obtain diester (II). (Ii) the compound (III) is obtained by cyclization under the action of sodium hydride in dimethylformamide. (Iii) hydrolysis and decarboxylation to give ketorolac. Method 2: The compound (IV) was obtained by reacting aminoethanol with dimethyl 3-oxoglutarate. Heating cyclization of (IV) and bromoacetaldehyde gave compound (V). (V) after methanesulfonylation, the compound (VI) is obtained by re-iodination. (Vi) the compound (VII) is obtained by cyclization under the action of a base. (Vii) after hydrolysis, the compound (VIII) is obtained by re-Mono-esterification and decarboxylation. (Viii) acylation with benzoyldimethylamine followed by hydrolysis to give ketorolac. Method 3: pyrrole was reacted with N-benzoyl morpholine in dichloroethane under the action of phosphorus oxychloride to obtain 2-benzoyl pyrrole, The yield was 72.3%. Potassium permanganate, manganese diacetate tetrahydrate and glacial acetic acid were warmed together and acetic anhydride was dripped carefully. After dropping, the mixture was cooled to room temperature, triethyl orthoformate, 2-benzoylpyrrole and anhydrous sodium acetate were added, and the mixture was stirred at 65 ° C. Under nitrogen. Triethyl orthoformate derivative was obtained after treatment in 86% yield. Under the action of potassium carbonate and tetra-n-butyl ammonium bromide, the derivative was refluxed in dichloroethane to obtain a cyclization product; Ketorolac was obtained after hydrolysis and acidification without purification in 66.7% yield. |
Last Update：2024-04-09 20:49:11
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Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Spot supply
Product Name: Ketorolac trometamol for peak identification Visit Supplier Webpage Request for quotationCAS: 74103-06-3
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
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