When heated to decomposition it emits acrid smoke and irritating fumes.
解离常数：
pKa = 12.9; pKb = 9.52 (25 °C)
碰撞截面：
238.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]
计算性质
辛醇/水分配系数(LogP)：
-9
重原子数：
42
可旋转键数：
9
环数：
4.0
sp3杂化的碳原子比例：
1.0
拓扑面积：
353
氢给体数：
13
氢受体数：
19
ADMET
代谢
新霉素的代谢信息有限，因为药物给药后系统性吸收有限。认为代谢可以忽略不计。
There is limited information on the metabolism of neomycin, as there is limited systemic absorption following drug administration. Metabolism is deemed to be negligible.
来源:DrugBank
代谢
氨基糖苷类药物不被代谢，主要通过肾小球滤过作用以原形在尿液中排出。/氨基糖苷类/
Aminoglycosides are not metabolized and are excreted unchanged in the urine primarily by glomerular filtration. /Aminoglycosides/
Neomycin undergoes negligible biotransformation after parenteral administration.
Route of Elimination: The small absorbed fraction is rapidly distributed in the tissues and is excreted by the kidney in keeping with the degree of kidney function.
Half Life: 2 to 3 hours
IDENTIFICATION AND USE: Neomycin is an aminoglycoside antibiotic. It is used in veterinary medicine as a bactericidal drug. HUMAN EXPOSURE AND TOXICITY: Prolonged administration could result in sufficient systemic drug levels to produce neurotoxicity, ototoxicity and/or nephrotoxicity. Dermatitis is usually caused by ointment with 0.5% neomycin. However, penetration of neomycin through normal skin is so slow that only half of those who are clinically sensitive will develop a positive patch test reaction to 0.5% neomycin. Characteristic lesions of the corneal epithelium in the form of tiny snowflakes, usually associated with sensation of irritation, may develop and may persist for weeks after application of neomycin to the eye is discontinued. Delayed-onset irreversible deafness, renal failure and death due to neuromuscular blockade (regardless of the status of renal function) have been reported following irrigation of both small and large surgical fields with minute quantities of neomycin. If renal insufficiency develops during oral therapy, consideration should be given to reducing the drug dosage or discontinuing therapy. Serious sensitivity reactions, such as anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, angioedema, and Stevens-Johnson syndrome, have been reported rarely in patients receiving aminoglycosides; fatalities have occurred rarely. Cross-sensitivity occurs among the aminoglycosides. In human lymphocytes neomycin tested negative for sister chromatid exchanges, but it was positive in chromosome aberration assay. ANIMAL STUDIES: No significant irritation was observed 24 hours after the intrapleural administration of single doses of solutions of 1 mL neomycin sulfate (0-100 mg/mL) to guinea pigs. Twelve dogs were injected intramuscularly with 24, 48, or 96 mg/kg bw/day neomycin. At the highest dose all dogs died within 1-3 weeks. Blood urea nitrogen was increased and renal function impaired as shown by decreased phenolsulfonphthalein excretion. There was no evidence of carcinogenicity in rats. In a 3-generation reproductive toxicity study groups of rats (40-20/sex/group) were administered neomycin sulfate via the diet at 0, 6.25, 12.5 or 25 mg/kg bw/day. Through all generations no treatment-related effects were observed in any of the parameters evaluated. Neomycin was positive in cytogenetic assay in mice bone marrow.
Aminoglycosides like neomycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically neomycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.
Oral and topical therapy with neomycin has not been linked serum alkaline phosphatase or aminotransferase elevations, and no convincing cases of symptomatic or icteric hepatotoxicity due to oral neomycin have been published. The poor absorption of neomycin makes it unlikely that systemic levels of the drug that might cause liver injury could be achieved. Furthermore, the ototoxicity of absorbed neomycin is likely to supervene before liver toxicity would occur.
References to the safety and potential hepatotoxicity of neomycin are provided in the Overview section on the Aminoglycosides.
Drug Class: Aminoglycosides
Other Drugs in the Class: Amikacin, Gentamicin, Plazomicin, Streptomycin, Tobramycin
Neomycin is poorly absorbed from the gastrointestinal tract. Gastrointestinal absorption of the drug may be increased if inflammatory or ulcerative gastrointestinal disease is present.
来源:DrugBank
吸收、分配和排泄
消除途径
少量的新霉素被吸收后由肾脏排出。未被吸收的药物部分以原形在粪便中排出。
The small absorbed fraction of neomycin is excreted by the kidney. The unabsorbed portion of the drug is excreted unchanged in the feces.
The small fraction of absorbed neomycin is rapidly distributed in the tissues. The amount of systemically absorbed neomycin is reported to increase cumulatively with each repeated dose administered until a steady state is reached.
来源:DrugBank
吸收、分配和排泄
清除
新霉素的清除率方面的信息有限。
There is limited information on the clearance rate of neomycin.
Neomycin sulfate is poorly absorbed from the normal gastrointestinal tract. The small absorbed fraction is rapidly distributed in the tissues and is excreted by the kidney in keeping with the degree of kidney function. The unabsorbed portion of the drug (approximately 97%) is eliminated unchanged in the feces.
氨基糖苷类抗生素模拟物的快速组合合成：在多组分缩合中使用聚乙二醇连接的胺和 Neamine 衍生的醛作为发现 HIV RNA Rev 响应元件的新抑制剂的策略
摘要：
使用新霉素衍生的醛、叔丁基异氰化物或异氰乙酸甲酯、甘氨酸缀合的聚乙二醇 (PEG) 甲基醚和各种 Cbz-N 保护的氨基酸，无需色谱法即可快速制备新霉素 B 模拟物文库作为 Ugi 型一锅反应的底物。通过在乙醚中沉淀分离与PEG连接的产物。同时进行碱催化水解和脱氧乙酰化，然后进行氢化，可以轻松访问新霉素 B 模拟物库，该库已筛选与 HIV mRNA (RRE) 的 Rev 响应元件结合。发现一些产品比尼胺活性更高，IC50 值在微摩尔范围内。
新霉素生物合成的最后一步是在新霉素 C 的 C-5‴ 处差向异构化以产生新霉素 B。负责差向异构化的候选酶是假定的自由基 S-腺苷-L-甲硫氨酸 (SAM) 酶 NeoN，它是独一无二的在新霉素生物合成基因簇中编码，并且在新霉素生物合成中仍然是未指定的蛋白质。重构和还原的 NeoN 在 SAM 存在下显示出预期的差向异构化活性。在差向异构化过程中，消耗 1 当量的 SAM 将新霉素 C 转化为新霉素 B。通过检测来自基于氧化氘的缓冲液中氘原子的掺入，新霉素 C 对差向异构化具有反应性的位点被清楚地证实为 C-5‴解决方案。更多，NeoN 半胱氨酸残基的丙氨酸扫描显示 C249 是一个关键的氨基酸残基，它提供一个氢原子来完成差向异构化。此外，在 SAM 和新霉素 C 存在下对 C249A 变体的电子顺磁共振分析表明，在新霉素 C 的 C-5‴ 处生成了自由基中间体。 因此，本研究清楚地说明了新霉素
Biosynthesis of the triterpenoids, botryococcenes and tetramethylsqualene in the B race of Botryococcus braunii via the non-mevalonate pathway
摘要：
The green microalga Botryococcus braunii race B accumulates two types of triterpenoid hydrocarbons, botryococcenes and tetramethylsqualene. Both triterpenoids are synthesized via the non-mevalonate pathway. (C) 2003 Elsevier Ltd. All rights reserved.
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.
The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5′-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.
[EN] SUBSTITUTED BENZYLAMINE COMPOUNDS, THEIR USE IN MEDICINE, AND IN PARTICULAR THE TREATMENT OF HEPATITIS C VIRUS (HCV) INFECTION<br/>[FR] COMPOSÉS DE BENZYLAMINE SUBSTITUÉS, LEUR UTILISATION EN MÉDECINE, EN PARTICULIER DANS LE TRAITEMENT D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE C (VHC)
申请人：ASTEX THERAPEUTICS LTD
公开号：WO2013064538A1
公开（公告）日：2013-05-10
The invention provides compounds of the formula (I): or a salt, N-oxide or tautomer thereof, wherein A is CH, CF or nitrogen; E is CH, CF or nitrogen; and R0 is hydrogen or C1-2 alkyl; R1a is selected from CONH2; CO2H; an optionally substituted acyclic C1-8 hydrocarbon group; and an optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1, 2, 3 or 4 are heteroatom ring members selected from O, N and S; R2 is selected from hydrogen and a group R2a; R2a is selected from an optionally substituted acyclic d-8 hydrocarbon group; an optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1 or 2 ring members are heteroatom ring members selected from O, N and S; and an optionally substituted bicyclic heterocyclic group of 9 or 10 ring members, of which 1 or 2 ring members are nitrogen atoms; wherein at least one of R1 and R2 is other than hydrogen; R3 is an optionally substituted 3- to 10-membered monocyclic or bicyclic carbocyclic or heterocyclic ring containing 0, 1, 2 or 3 heteroatom ring members selected from N, O and S; R4a is selected from halogen; cyano; C1-4 alkyl optionally substituted with one or more fluorine atoms; C1-4 alkoxy optionally substituted with one or more fluorine atoms; hydroxy-C1-4 alkyl; and C1-2 alkoxy-C1-4 alkyl; R5 is selected from hydrogen and a substituent R5a; and R5a is selected from C1-2 alkyl optionally substituted with one or more fluorine atoms; C1-3 alkoxy optionally substituted with one or more fluorine atoms; halogen; cyclopropyl; cyano; and amino, The compounds have activity against hepatitis C virus and can be used in the prevention or treatment of hepatitis C viral infections.
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。
New Drug Delivery System for Crossing the Blood Brain Barrier
申请人：Lipshutz H. Bruce
公开号：US20070203080A1
公开（公告）日：2007-08-30
New ubiquinol analogs are disclosed, as well as methods of using these compounds to deliver drug moieties to the body.
