IDENTIFICATION AND USE: Lisinopril is angiotensin-converting enzyme (ACE) inhibitor, antihypertensive and cardiotonic agent. HUMAN EXPOSURE AND TOXICITY: The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Marked hypotension may occur in patients with congestive heart failure-potential for myocardial infarction or stroke in those with acute myocardial infarction or ischemic cardiovascular or cerebrovascular disease. Rare ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice or hepatitis; may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including lisinopril, who develop jaundice or marked elevations in hepatic enzymes should discontinue the drug and receive appropriate monitoring. Hyperkalemia can develop, especially in those with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration. Sensitivity reactions, including anaphylactoid reactions and angioedema (including laryngeal edema, tongue edema), are potentially fatal. 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. ANIMAL STUDIES: There was no evidence of a tumorigenic effect when lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg per kg per day or for 92 weeks to male and female mice at doses up to 135 mg per kg per day. Lisinopril treatment in male rats resulted in a marked decrease in sperm density, sperm motility and zona pellucida penetration. Acrosome reaction by spermatozoa obtained from drug-treated animals was significantly lower when compared with spermatozoa from normal animals. The developmental toxicity of lisinopri have been tested in mice and rabbits. In mice, the incidence of resorptions increased at all dosage levels. No treatment-related adverse effects were found on litter sizes of live fetuses and mean fetal weights. In rabbits, mean fetal weights were normal, although ossification was retarded at all dosage levels. External, skeletal and visceral examinations did not reveal any teratogenic potential at any dosage level in mice and rabbits. Lisinopril was not mutagenic in the Ames microbial mutagen test with or without metabolic activation. It was also negative in a forward mutation assay using Chinese hamster lung cells. Lisinopril did not produce single strand DNA breaks in an in vitro alkaline elution rat hepatocyte assay. In addition, lisinopril did not produce increases in chromosomal aberrations in an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow. There were 1781 dogs exposed to lisinopril and 156 that became symptomatic. The most common clinical signs included: lethargy (24%), tachycardia (18%), vomiting (14%) and hypotension (13%). Of the 98 cats, 7 were symptomatic with 29% hypertensive 29% tachycardic and 29% vomiting.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
肝毒性
Lisinopril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations (
Lisinopril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations (
Lisinopril is 6-60% orally bioavailable with an average of 25% bioavailability. Lisinopril reaches a Cmax of 58ng/mL with a Tmax of 6-8h. Lisinopril's absorption is not affected by food.
来源:DrugBank
吸收、分配和排泄
消除途径
Lisinopril 完全通过尿液排出。
Lisinopril is entirely eliminated exclusively in the urine.
来源:DrugBank
吸收、分配和排泄
分布容积
赖诺普利的表观分布容积为124L。
The apparent volume of distribution of lisinopril is 124L.
A 30kg child has a typical clearance of 10L/h, which increases with renal function. The mean renal clearance of lisinopril in healthy adult males is 121mL/min.
来源:DrugBank
吸收、分配和排泄
稳态在健康志愿者每天两次剂量（每隔24小时）后达到。该药物不被代谢，而是通过肾脏消除。
Steady state is attained after two daily doses (every 24 hours) in healthy volunteers. The drug is not metabolized but is eliminated via the kidneys.
Material Safety Data Sheet Section 1. Identification of the substance Product Name: Lisinopril Synonyms: Section 2. Hazards identification Harmful by inhalation, in contact with skin, and if swallowed. Section 3. Composition/information on ingredients. Ingredient name: Lisinopril CAS number: 76547-98-3 Section 4. First aid measures Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. If irritation persists, seek medical attention. Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical attention. Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention. Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention. Section 5. Fire fighting measures In the event of a fire involving this material, alone or in combination with other materials, use dry powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus should be worn. Section 6. Accidental release measures Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national standards. Respiratory precaution: Wear approved mask/respirator Hand precaution: Wear suitable gloves/gauntlets Skin protection: Wear suitable protective clothing Eye protection: Wear suitable eye protection Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container for disposal. See section 12. Environmental precautions: Do not allow material to enter drains or water courses. Section 7. Handling and storage Handling: This product should be handled only by, or under the close supervision of, those properly qualified in the handling and use of potentially hazardous chemicals, who should take into account the fire, health and chemical hazard data given on this sheet. Store in closed vessels, refrigerated. Storage: Section 8. Exposure Controls / Personal protection Engineering Controls: Use only in a chemical fume hood. Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles. General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse. Section 9. Physical and chemical properties Appearance: Not specified Boiling point: No data No data Melting point: Flash point: No data Density: No data Molecular formula: C21H31N3O5 Molecular weight: 405.5 Section 10. Stability and reactivity Conditions to avoid: Heat, flames and sparks. Materials to avoid: Oxidizing agents. Possible hazardous combustion products: Carbon monoxide, nitrogen oxides. Section 11. Toxicological information No data. Section 12. Ecological information No data. Section 13. Disposal consideration Arrange disposal as special waste, by licensed disposal company, in consultation with local waste disposal authority, in accordance with national and regional regulations. Section 14. Transportation information Non-harzardous for air and ground transportation. Section 15. Regulatory information No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302, or have known CAS numbers that exceed the threshold reporting levels established by SARA Title III, Section 313.
DISUBSTITUTED TRIFLUOROMETHYL PYRIMIDINONES AND THEIR USE
申请人：BAYER PHARMA AKTIENGESELLSCHAFT
公开号：US20160221965A1
公开（公告）日：2016-08-04
The present application relates to novel 2,5-disubstituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.
[EN] SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] COMPOSÉS DE SULFONYLE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
申请人：AMGEN INC
公开号：WO2013123444A1
公开（公告）日：2013-08-22
The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
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.
NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
申请人：Ryono Denis E.
公开号：US20080009465A1
公开（公告）日：2008-01-10
Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure
wherein
is a heteroaryl ring;
R
4
is —(CH
2
)
n
-Z-(CH
2
)
m
—PO(OR
7
)(OR
8
), —(CH
2
)
n
Z-(CH
2
)
m
—PO(OR
7
)R
g
, —(CH
2
)
n
-Z-(CH
2
)
m
—OPO(OR
7
)R
g
, —(CH
2
)
n
Z—(CH
2
)
m
—OPO(R
9
)(R
10
), or —(CH
2
)
n
Z—(CH
2
)
m
—PO(R
9
)(R
10
);
R
5
and R
6
are independently selected from H, alkyl and halogen;
Y is R
7
(CH
2
)
s
or is absent; and
X, n, Z, m, R
4
, R
5
, R
6
, R
7
, and s are as defined herein; or a pharmaceutically acceptable salt thereof.
A method for treating diabetes and related diseases employing the above compounds is also provided.
提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构：
其中
是杂环芳基环；
R
4
为—(CH
2
)
n
-Z-(CH
2
)
m
—PO(OR
7
)(OR
8
)、—(CH
2
)
n
Z-(CH
2
)
m
—PO(OR
7
)R
g
、—(CH
2
)
n
-Z-(CH
2
)
m
—OPO(OR
7
)R
g
、—(CH
2
)
n
Z—(CH
2
)
m
—OPO(R
9
)(R
10)
或—(CH
2
)
n
Z—(CH
2
)
m
—PO(R
9
)(R
10)
；
R
5
和R
6
分别选择自H、烷基和卤素；
Y为R
7
(CH
2
)
s
或不存在；以及
X、n、Z、m、R
4
、R
5
、R
6
、R
7
和s如本文所定义；或其药用盐。
还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
