Cleavage of the ester group of trandolapril, primarily in the liver, is responsible for conversion to trandolaprilat, the active metabolite. Seven other metabolites, including diketopiperazine and glucuronide conjugated derivatives of trandolapril and trandolaprilat, have been identified.
Trandolapril's angiotensin-converting enzyme (ACE)-inhibiting activity is primarily due to its diacid metabolite, trandolaprilat. Cleavage of the ester group of trandolapril, primarily in the liver, is responsible for conversion.
After oral administration of trandolapril, about 33% of parent drug and metabolites are recovered in urine, mostly as trandolaprilat, with about 66% in feces. ... In addition to trandolaprilat, at least 7 other metabolites have been found, principally glucuronides or deesterification products.
IDENTIFICATION AND USE: Trandolapril is a colorless, crystalline solid. Trandolapril tablets are indicated for the treatment of hypertension. HUMAN STUDIES: In humans, the most likely clinical manifestation would be symptoms attributable to severe hypotension. Symptoms expected with angiotensin-converting enzyme (ACE) inhibitors are hypotension, hyperkalemia, and renal failure. Rare angiotensin-converting enzyme (ACE) inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice may occur; this may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including trandolapril, who develop jaundice or marked elevations in hepatic enzymes should discontinue the drug and receive appropriate monitoring. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. ANIMAL STUDIES: In dogs, an oral dose of 1000 mg/kg did not cause mortality and abnormal clinical signs were not observed. In rats, an oral dose of 5000 mg/kg caused low mortality (1 male out of 5; 0 females). A perinatal and postnatal study was performed in female Sprague-Dawley rats treated orally with trandolapril at dosage levels of 3, 30 and 300 mg/kg/day from day 17 of pregnancy to postpartum day 21. Incidence of dilatation of renal pelvis with higher value in kidney weight was increased in offspring in the 30 and 300 mg/kg dosage groups, and water consumption at the same dosage groups was higher than that of the control group. Body weight gain in offspring was depressed in each treated group and viability of offspring from postpartum day 0 to day 4 was slightly decreased in the 30 and 300 mg/kg dosage groups comparing with that of the control group. No adverse effects were observed on the other postnatal development of the offspring, such as differentiation, sexual maturation, reflex, motor activity, emotionality, learning ability and reproductive performance. No adverse effects were detected in the second generation offspring.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
肝毒性
Trandolapril，像其他ACE抑制剂一样，与血清转氨酶升高的低发生率有关（
Trandolapril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations (
After oral administration of trandolapril, about 33% of parent drug and metabolites are recovered in urine, mostly as trandolaprilat, with about 66% in feces.
来源:DrugBank
吸收、分配和排泄
分布容积
18 L
18 L
来源:DrugBank
吸收、分配和排泄
清除
52升/小时 [在大约2毫克静脉注射剂量后]
52 L/h [After approximately 2 mg IV doses]
来源:DrugBank
吸收、分配和排泄
/MILK/ Trandolapril 及其代谢物在大鼠乳汁中有分布。
/MILK/ Trandolapril and its metabolites are distributed into milk in rats.
Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE Product identifiers Product name : Trandolapril CAS-No. : 87679-37-6 Relevant identified uses of the substance or mixture and uses advised against Identified uses : Laboratory chemicals, Manufacture of substances Section 2. HAZARDS IDENTIFICATION Classification of the substance or mixture Not a dangerous substance according to GHS. This substance is not classified as dangerous according to Directive 67/548/EEC. Label elements The product does not need to be labelled in accordance with EC directives or respective national laws. Other hazards - none Section 3. COMPOSITION/INFORMATION ON INGREDIENTS Substances Synonyms : (2S,3aR,7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]- 1-oxopropyl]octahydro-1H-Indole-2-carboxylic acid Mavik Formula : C24H34N2O5 Molecular Weight : 430,54 g/mol Component Concentration Trandolapril CAS-No. 87679-37-6 - Section 4. FIRST AID MEASURES Description of first aid measures If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. In case of skin contact Wash off with soap and plenty of water. In case of eye contact Flush eyes with water as a precaution. If swallowed Never give anything by mouth to an unconscious person. Rinse mouth with water. Most important symptoms and effects, both acute and delayed To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. Indication of immediate medical attention and special treatment needed no data available Section 5. FIRE-FIGHTING MEASURES Extinguishing media Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special hazards arising from the substance or mixture Carbon oxides, nitrogen oxides (NOx) Precautions for fire-fighters Wear self contained breathing apparatus for fire fighting if necessary. Further information no data available Section 6. ACCIDENTAL RELEASE MEASURES Personal precautions, protective equipment and emergency procedures Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions Do not let product enter drains. Methods and materials for containment and cleaning up Sweep up and shovel. Keep in suitable, closed containers for disposal. Reference to other sections For disposal see section 13. Section 7. HANDLING AND STORAGE Precautions for safe handling Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire protection. Conditions for safe storage, including any incompatibilities Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Specific end uses no data available Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION Control parameters Components with workplace control parameters Exposure controls Appropriate engineering controls General industrial hygiene practice. Personal protective equipment Eye/face protection Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Body Protection Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Respiratory protection Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). Section 9. PHYSICAL AND CHEMICAL PROPERTIES Information on basic physical and chemical properties a) Appearance Form: powder b) Odour no data available c) Odour Threshold no data available d) pH no data available e) Melting/freezing point no data available f) Initial boiling point and no data available boiling range g) Flash point no data available h) Evaporation rate no data available i) Flammability (solid, gas) no data available j) Upper/lower no data available flammability or explosive limits k) Vapour pressure no data available l) Vapour density no data available m) Relative density no data available n) Water solubility no data available o) Partition coefficient: n- log Pow: 2,444 octanol/water p) Autoignition no data available temperature q) Decomposition no data available temperature r) Viscosity no data available s) Explosive properties no data available t) Oxidizing properties no data available Other safety information no data available Section 10. STABILITY AND REACTIVITY Reactivity no data available Chemical stability no data available Possibility of hazardous reactions no data available Conditions to avoid no data available Incompatible materials Strong oxidizing agents Hazardous decomposition products Other decomposition products - no data available Section 11. TOXICOLOGICAL INFORMATION Information on toxicological effects Acute toxicity LD50 Oral - rat - > 5.000 mg/kg Skin corrosion/irritation no data available Serious eye damage/eye irritation no data available Respiratory or skin sensitization no data available Germ cell mutagenicity no data available Carcinogenicity IARC: No component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by IARC. Reproductive toxicity no data available Specific target organ toxicity - single exposure no data available Specific target organ toxicity - repeated exposure no data available Aspiration hazard no data available Potential health effects Inhalation May be harmful if inhaled. May cause respiratory tract irritation. Ingestion May be harmful if swallowed. Skin May be harmful if absorbed through skin. May cause skin irritation. Eyes May cause eye irritation. Signs and Symptoms of Exposure To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. Additional Information RTECS: NL6015178 Section 12. ECOLOGICAL INFORMATION Toxicity no data available Persistence and degradability no data available Bioaccumulative potential no data available Mobility in soil no data available Results of PBT and vPvB assessment no data available Other adverse effects no data available Section 13. DISPOSAL CONSIDERATIONS Waste treatment methods Product Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging Dispose of as unused product. Section 14. TRANSPORT INFORMATION UN-Number ADR/RID: - IMDG: - IATA: - UN proper shipping name ADR/RID: Not dangerous goods IMDG: Not dangerous goods IATA: Not dangerous goods Transport hazard class(es) ADR/RID: - IMDG: - IATA: - Packaging group ADR/RID: - IMDG: - IATA: - Environmental hazards ADR/RID: no IMDG Marine pollutant: no IATA: no Special precautions for users no data available SECTION 15 - REGULATORY INFORMATION N/A
SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS
申请人：BLUM Andreas
公开号：US20140135309A1
公开（公告）日：2014-05-15
This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I
wherein Ar, R
1
and R
2
are as defined herein, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.
[EN] SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS<br/>[FR] QUINAZOLINES SUBSTITUÉES PAR SULFOXIMINE POUR COMPOSITIONS PHARMACEUTIQUES
申请人：BOEHRINGER INGELHEIM INT
公开号：WO2014072244A1
公开（公告）日：2014-05-15
This invention relates to novel sulfoximine substituted quinazoline derivatives of formula (I), wherein Ar, R1 and R2 are as defined in the description and claims, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.
[EN] HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF STRESS-RELATED CONDITIONS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES POUR LE TRAITEMENT D'ÉTATS LIÉS AU STRESS
申请人：OTSUKA PHARMA CO LTD
公开号：WO2010137738A1
公开（公告）日：2010-12-02
The present invention provides a novel heterocyclic compound. A heterocyclic compound represented by general formula (1) wherein, R1 and R2, each independently represent hydrogen; a phenyl lower alkyl group that may have a substituent(s) selected from the group consisting of a lower alkyl group and the like on a benzene ring and/or a lower alkyl group; or a cyclo C3-C8 alkyl lower alkyl group; or the like; R3 represents a lower alkynyl group or the like; R4 represents a phenyl group that may have a substituent(s) selected from the group consisting of a 1,3,4-oxadiazolyl group that may have e.g., halogen or a heterocyclic group selected from pyridyl group and the like; the heterocyclic group may have at least one substituent(s) selected from a lower alkoxy group and the like or a salt thereof.
[EN] SULFOXIMINE SUBSTITUTED PYRROLOTRIAZINES FOR PHARMACEUTICAL COMPOSITIONS<br/>[FR] PYRROLOTRIAZINES À SUBSTITUTION SULFOXIMINE POUR COMPOSITIONS PHARMACEUTIQUES
申请人：BOEHRINGER INGELHEIM INT
公开号：WO2015091156A1
公开（公告）日：2015-06-25
This invention relates to novel sulfoximine substituted pyrrolotriazine derivatives of formula wherein Ar, R1 and R2 are as defined in the description and claims, and their use as MNK1 (MNK1 a or MNK1 b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1 a or MNK1 b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.
[EN] SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS<br/>[FR] QUINAZOLINES SUBSTITUÉES PAR UNE SULFOXIMINE DESTINÉES À DES COMPOSITIONS PHARMACEUTIQUES
申请人：BOEHRINGER INGELHEIM INT
公开号：WO2015169677A1
公开（公告）日：2015-11-12
The application relates to novel sulfoximine substituted quinazoline derivatives of formula (I) wherein Ar, R1, R2 and R3 are as defined in the description and claims, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.
