Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
Tadalafil
CIALIS · Tadanafil · Tadalafei · Taladafil · tadanafei · Calais · Tadalfil · Tildenafil
식별자 및 물리적 특성
| CAS No. | 171596-29-5 |
|---|---|
| 분자식 | C22H19N3O4 |
| 평균 분자량 | 389.4 g/mol |
| 단동위원소 질량 | 389.13755609 g/mol |
| SMILES | CN1CC(=O)N2[C@H](c3ccc4c(c3)OCO4)c3[nH]c4ccccc4c3C[C@@H]2C1=O |
| InChIKey | WOXKDUGGOYFFRN-IIBYNOLFSA-N |
| PubChem CID | 110635 |
| ChEMBL | CHEMBL779 |
| ChEBI | CHEBI:71940 |
| EC No. | 687-782-2 |
| DTXSID | DTXSID9046786 |
화학 및 물리적 성질
| XLogP | 2.3 |
|---|---|
| 극성 표면적 | 74.9 |
| 수소 결합 공여자 수 | 1 |
| 수소 결합 수용자 수 | 4 |
| 회전 가능 결합 수 | 1 |
| 무거운 원자 수 | 29 |
| 형식 전하 | 0 |
| 복잡도 | 702 |
| 의약품 | Pharmaceuticals -> Listed in ZINC15 |
| LogP(분배 계수) | log Kow = 1.42 /Estimated/1.72.6 |
| 용해도 | Practically insoluble in waterIn water, 220 mg/L at 25 °C /Estimated/2.50e-01 g/L3.2 [ug/mL] (The mean of the results at pH 7.4)DMSO: 용해성20mg/mL, 투명 |
| Human Drugs | FDA approved drugs -> Active ingredientEMA approved medicines: Human medicine |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| 녹는점 | 301-302 °C301 - 302 °C298-300°C |
| 증기압 | 2.2X10-14 mm Hg at 25 °C /Estimated/ |
| 헨리 상수 | Henry's Law constant = 5.0X10-18 atm-cu m/mol @ 25 °C /Estimated/2.0×1012 mol/(m3Pa) at 25℃, HSDB (2015) |
| Physical Description | Solid |
| Dissociation Constants | pKa = 0.85 /Estimated/ |
| Collision Cross Section | 199.71 Ų [M+K]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]189.4 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]188.7 Ų [M+H]+ [CCS Type: TW |
| Other Experimental Properties | Hydroxyl radical reaction rate constant = 2.9X10-10 cu cm/molec-sec at 25 °C /Estimated/ |
| 끓는 점 | 679.1±55.0 °C(Predicted) |
| 밀도 | 1.51±0.1 g/cm3(Predicted) |
| 인화점 | 2℃ |
| 저장 조건 | Sealed in dry,2-8°C |
| 물리적 상태 | 가루 |
| pKa(산도 계수) | 16.68±0.40(Predicted) |
| 색상 | 흰색에서 베이지색 |
| BCS Class | 4 |
| 안정성 | 메탄올에서는 불안정함 |
| 주요 응용 | 의약품(소분자) |
| InChI | InChI=1S/C22H19N3O4/c1-24-10-19(26)25-16(22(24)27)9-14-13-4-2-3-5-15(13)23-20(14)21(25)12-6-7-17-18(8-12)29-11-28-17/h2-8,16,21,23H,9-11H2,1H3/t16-,21-/m1/s1 |
| InChIKey | WOXKDUGGOYFFRN-IIBYNOLFSA-N |
| SMILES | N1C2=C(C=CC=C2)C2C[C@]3([H])C(=O)N(C)CC(=O)N3[C@H](C3=CC=C4OCOC4=C3)C1=2 |
화학적 성질
White to Off-White Cyrstalline Solid
안전 및 규제
| GHS 분류 | WarningH302 (54.8%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 104 reports by companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| FDA 요건 | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl tadalafil, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Hazard Classes and Categories | Acute Tox. 4 (54.8%) |
| 처리 방법 | SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations. |
| 상호 작용 | Simultaneous administration of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduced the apparent rate of absorption of tadalafil without altering the exposure (AUC) to tadalafil.A significant interaction between tadalafil and nitroglycerin was observed to last up to 48 hoursat least 48 hours should elapse after the last dose of tadalafil before nitrate administration is considered.Administration of tadalafil to patients who are using any form of organic nitrates, either regularly and/or intermittently, is contraindicatedin clinical pharmacology studies tadalafil was shown to potentiate the hypotensive effects of nitratesthis is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway.The safety and efficacy of combinations of tadalafil and other erectile dysfunctions have not been studieduse of combinations is not recommended.For more Interactions (Complete) data for TADALAFIL (15 total), please visit the HSDB record page. |
| Hepatotoxicity | Despite fairly extensive use, tadalafil has been linked to only rare reports of serum aminotransferase elevations and clinically apparent liver injury. In a single case report, tadalafil was linked to cholestatic hepatitis arising within a few days of starting the medication. Immunoallergic features and autoantibodies were not present. The injury was self-limiting without residual evidence of bile duct injury. The related PDE5 inhibitor, sildenafil, has also been associated with rare cases of acute cholestatic liver injury with jaundice. |
| 환경 거동 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 53,000(SRC), determined from a structure estimation method(2), indicates that tadalafil is expected to be immobile in soil(SRC). Volatilization of tadalafil from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.0X10-18 atm-cu m/mole(SRC), determined by a fragment constant estimation method(3). Tadalafil is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-14 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 53,000(SRC), determined from a structure estimation method(2), indicates that tadalafil is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.0X10-18 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 2.5(SRC), from an estimated log Kow of 1.42(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2005).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tadalafil, which has an estimated vapor pressure of 2.2X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase tadalafil may be removed from the air by wet and dry deposition(SRC). |
| 유해 작용 | Common Adverse Effects |
| 독성 요약 | Signs and Symptoms of Overdose |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc for tadalafil can be estimated to be 53,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that tadalafil is expected to be immobile in soil. |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Single doses up to 500 mg have been given to healthy subjects, and multiple daily doses up to 100 mg have been given to patients. Adverse events were similar to those seen at lower doses./HUMAN EXPOSURE STUDIES/ Administration of tadalafil to patients who are using any form of organic nitrates, either regularly and/or intermittently, is contraindicatedin clinical pharmacology studies tadalafil was shown to potentiate the hypotensive effects of nitratesthis is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway./HUMAN EXPOSURE STUDIES/ Cardiovascular status of patients should be considered since there is a degree of risk associated with sexual activitytreatments for erectile dysfunction, including tadalafil, should not be used in men for whom sexual activity is inadvisable as a result of their underlying cardiac status./HUMAN EXPOSURE STUDIES/ Left Ventricular Outflow Obstruction -- Patients with left ventricular outflow obstruction, (e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators, including PDE5 inhibitors.For more Human Toxicity Excerpts (Complete) data for TADALAFIL (6 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Tadalafil's production and use in the treatment of erectile dysfunction(1) may result in its release to the environment through various waste streams(SRC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)TadalafilvLess-DILI-concern3Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Environmental Bioconcentration | An estimated BCF of 2.5 was calculated for tadalafil(SRC), using an estimated log Kow of 1.42(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). |
| Volatilization from Water/Soil | The Henry's Law constant for tadalafil is estimated as 5.0X10-18 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that tadalafil is expected to be essentially nonvolatile from water surfaces(2). Tadalafil's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Tadalafil is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-14 mm Hg(SRC), determined from a fragment constant method(3). |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Animal studies showed vascular inflammation in tadalafil-treated mice, rats, and dogs. In mice and rats, lymphoid necrosis and hemorrhage were seen in the spleen, thymus, and mesenteric lymph nodes ... In dogs, an increased incidence of disseminated arteritis was observed in 1- and 6-month studies at unbound tadalafil exposure of 1- to 54-fold above the human exposure (AUC) at the MRHD./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Tadalafil was not carcinogenic to rats or mice when administered daily for up to two years at doses up to 400 mg per kg per day. Systemic drug exposures, as measured by AUC of unbound tadalafil, were approximately 10-fold for mice, and 14- and 26-fold for male and female rats, respectively, the exposures in human males given Maximum Recommended Human Dose (MRHD)./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a 12-month dog study, no disseminated arteritis was observed, 2 dogs exhibited marked decreases in white blood cells (neutrophils) and moderate decreases in platelets with inflammatory signs at unbound tadalafil exposures of approximately 14- to 18-fold the human exposure at the MRHD./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In beagle dogs given tadalafil daily for 3 to 12 months, there was treatment-related non-reversible degeneration and atrophy of the seminiferous tubular epithelium in the testes in 20 to 100% of the dogs that resulted in decreased spermatogenesis in 40 to 75% of the dogs at doses of > or = 10 mg per kg per day. Systemic exposure (based on AUC) at no-observed-adverse-effect-level (NOAEL) (10 mg/kg/day) for unbound tadalafil was similar to that expected in humans at the MRHD.For more Non-Human Toxicity Excerpts (Complete) data for TADALAFIL (7 total), please visit the HSDB record page. |
| 수질 위해 등급(WGK) | 3 |
| RTECS 번호 | UQ4431050 |
| 관세 코드 | 2934990002 |
| 위험 문구(R) | 11-20/21/22-36 |
| 위험 표시 | F,Xn |
| 안전 문구(S) | 16-36/37 |
| 위험 등급 | Eye Irrit. 2Skin Irrit. 2STOT SE 3 |
| 저장 분류 | 11 - Combustible Solids |
| 유해 물질 데이터 | 171596-29-5(Hazardous Substances Data) |
용도
개요
Tadalafil (market name “Cialis” or “Adcirca”) was developed by American pharmaceutical company Lilly. It is a kind of PDE5 inhibitor used for the treatment of erectile dysfunction, benign prostatic hypertrophy and pulmonary arterial hypertension.The effect of Tadalafil is relaxing the blood vessels muscles and increasing the blood flow into the corpus cavernosum. Studies show that Cialis works very quickly, taking effect in around 15-20 minutes, and has a prolonged effect that can last for up to 36 hours. T1/2 is 17.5h.
일반 설명
Tadalafil, 171596-29-5, is a potent PDE5 inhibitor.It received FDA approval for the treatment of erectiledysfunction in December 2003. Because of its half-life of17.5 hours, it is marketed as a 36-hour treatment. Tadalafil ispredominantly metabolized by hepatic enzymes, includingCYP3A4. The concomitant use of CYP3A4 inhibitors suchas ritonavir, indinavir, ketoconazole, as well as moderateCYP3A inhibitors such as erythromycin have been shown toresult in significant increases in tadalafil plasma levels.Much like sildenafil, tadalafil is under clinical investigationfor managing PAH.