클로피브레이트
클로피브레이트 · 클로피브레이트(CLOFIBRATE) · ELPI · Cinnarizin · Fibrate · LIP1 · CPIB · EPIB
식별자 및 물리적 특성
| CAS No. | 637-07-0 |
|---|---|
| 분자식 | C12H15ClO3 |
| 평균 분자량 | 242.7 g/mol |
| 단동위원소 질량 | 242.07097202 g/mol |
| SMILES | CCOC(=O)C(C)(C)Oc1ccc(Cl)cc1 |
| InChIKey | KNHUKKLJHYUCFP-UHFFFAOYSA-N |
| PubChem CID | 2796 |
| ChEMBL | CHEMBL565 |
| ChEBI | CHEBI:3750 |
| EC No. | 211-277-4 |
| DTXSID | DTXSID3020336 |
| 현지명 | 클로피브레이트 |
화학 및 물리적 성질
| XLogP | 3.3 |
|---|---|
| 극성 표면적 | 35.5 |
| 수소 결합 공여자 수 | 0 |
| 수소 결합 수용자 수 | 3 |
| 회전 가능 결합 수 | 5 |
| 무거운 원자 수 | 16 |
| 형식 전하 | 0 |
| 복잡도 | 232 |
| 의약품 | Pharmaceuticals -> Listed in ZINC15 |
| LogP(분배 계수) | 3.33.39 |
| 냄새 | FAINT CHARACTERISTIC ODOR |
| 맛 | FAINT CHARACTERISTIC TASTE |
| 밀도 | 1.138-1.144 @ 20 °C1.14 g/mL at 25 °C(lit.) |
| Color/Form | OILCOLORLESS TO PALE YELLOW LIQ |
| 용해도 | InsolubleINSOL IN WATERSOL IN ALC, CHLOROFORMMISCIBLE WITH ACETONE, ETHER2.90e-02 g/LDMSO에서는 100mM까지 용해됩니다. |
| Human Drugs | FDA approved drugs -> Active ingredient |
| 끓는 점 | 148-150 °C @ 20 MM HG154 °C |
| 녹는점 | 118-119< 25 °C<25 °C |
| 굴절률 | INDEX OF REFRACTION: 1.500-1.505 @ 19.5-20.5 °C/DMAX ABSORPTION (DEHYDRATED ETHANOL): 226 NM (A= 910, 1%, 1 CM)280 NM (A= 87, 1%, 1 CM)288 NM (A= 62, 1%, 1 CM)n20/D 1.503 |
| Physical Description | Solid |
| 인화점 | 113 °C |
| 저장 조건 | 2-8°C |
| 물리적 상태 | 액체 |
| 색상 | 투명, 무색 |
| 용해도 | 97.08mg/L(상온) |
| Merck | 14,2377 |
| BRN | 1913459 |
| 주요 응용 | 법의학 및 독성학의약품(소분자) |
| InChI | 1S/C12H15ClO3/c1-4-15-11(14)12(2,3)16-10-7-5-9(13)6-8-10/h5-8H,4H2,1-3H3 |
| InChIKey | KNHUKKLJHYUCFP-UHFFFAOYSA-N |
| SMILES | CCOC(=O)C(C)(C)Oc1ccc(Cl)cc1 |
| NIST | Clofibrate(637-07-0) |
| EPA | Clofibrate (637-07-0) |
화학적 성질
Clear Colorless Oil
안전 및 규제
| GHS 분류 | DangerH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P354+P338, P317, P319, P321, P330, P332+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 42 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 규제 정보 | Hazard Traits - Carcinogenicity |
| 기타 안전 정보 | IMAP assessments - Propanoic acid, 2-(4-chlorophenoxy)-2-methyl-, ethyl ester: Environment tier I assessment |
| FDA 요건 | Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392). |
| Special Reports | COHEN AJ, GRASSO PREVIEW OF THE HEPATIC RESPONSE TO HYPOLIPIDEMIC DRUGS IN RODENTS AND ASSESSMENT OF ITS TOXICOLOGICAL SIGNIFICANCE TO MANFOOD COSMET TOXICOL 19 (5): 585 (1981). A REVIEW OF THE HEPATIC RESPONSE TO HYPOLIPIDEMIC DRUGS, INCLUDING CLOFIBRATE, IN RODENTS & ASSESSMENT OF THEIR TOXICOLOGICAL SIGNIFICANCE TO MAN. |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| 보관 조건 | Clofibrate liquid-filled capsules should be stored in well-closed, light-resistant containers, @ a temp less than 40 °C. preferably @ 15-30 °Cfreezing of the liquid-filled capsules should be avoided. |
| 처리 방법 | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| 상호 작용 | ONE CASE REPORT HAS APPEARED DESCRIBING A PATIENT WITH TYPE-IV HYPERLIPOPROTEINEMIA CONTROLLED ON CLOFIBRATE THERAPY WHO DEVELOPED A RETURN OF ELEVATED SERUM CHOLESTEROL AND TRIGLYCERIDE AFTER TAKING AN ORAL CONTRACEPTIVE. |
용도
개요
Researchers in France observed in 1953 that structures derived from dehydrocholic acid, phenylethyl acetic acid, and certain other disubstituted acetic acids exhibited hypocholesterolemic properties in rats and humans. Several years later, Thorp and Waring discovered clof ibrate as an effective compound for lowering lipids in animal models, with minimal toxicity. Its mode of action was initially attributed to seasonal variations in adrenal and thyroid function, and the administration of androsterone was found to potentiate the hypocholesterolemic effect of this compound. Subsequently, several clinical trials were performed which showed that clofibrate decreases lipid levels in hypercholesterolemic patients, mainly as the result of a reduction in the very-low-density lipoprotein (VLDL), and less in the low-density lipoprotein (LDL) fraction, and that the coadministration of androsterone was not necessary for its hypolipidemic effect. Despite reported hepatomegaly in rats following long-term treatment with clofibrate, this drug was approved in the United States in 1967 for the treatment of hyperlipidemias. Clofibrate can be chemically synthesized by the condensation of phenol with ethyl 2-chloro-2-methylpropionate in the presence of a dehydrochlorinating agent, followed by chlorination and purification. It can also be synthesized by the condensation of p-chlorophenol with acetone and chloroform followed by esterifying the resultant acid to give clofibrate.
용도
Clofibrate is a lipid-lowering agent (antilipidemic) used for controlling high cholesterol (anticholesteremic) and triacylglyceride levels in the blood. It increases lipoprotein lipase activity to promote the conversion of VLDL to LDL, thereby reducing VLDL levels. It is indicated only in subjects with increased concentrations of VLDL and intermediate-density lipoproteins (IDL) who have failed to respond adequately to gemfibrozil or nicotinic acid. Clofibrate is of limited utility for patients with either familial hypercholesterolemia or polygenic hypercholesterolemia, as comparatively more effective drugs are available for lowering the concentration of LDL in these patients.Clofibrate has no effect on hyperchylomicronemia, nor does it affect concentrations of high-density lipoproteins (HDL). Thus, clofibrate appears to have specific efficacy only in patients with familial type-III hyperlipoproteinemia. There is no substantial evidence proving efficacy of clofibrate in preventing deaths from coronary artery disease. Clofibrate has been used to prevent or control polydipsia, polyuria, and dehydration in a limited number of patients with mild to moderate neurohypophyseal diabetes insipidus. A 5-year multicenter study reported failure of clofibrate in reducing or preventing mortality in cardiovascular disorders, which has provided a setback for the prophylactic use of this drug.