Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Uremic toxins such as N-methyl-2-pyridone-5-carboxamide are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
健康影响
长期暴露于尿毒症毒素可能会导致多种疾病，包括肾脏损伤、慢性肾病和心血管疾病。
Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
[EN] COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS
申请人：YUMANITY THERAPEUTICS INC
公开号：WO2020198026A1
公开（公告）日：2020-10-01
The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.
The present invention relates to compounds of Formula (I) that are useful as inhibitors of the activity of the ubiquitin specific protease USP19. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in therapy.
[EN] HETEROCYCLIC CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES HÉTÉROCYCLIQUES DU RÉCEPTEUR DU CGRP
申请人：MERCK SHARP & DOHME
公开号：WO2015161014A1
公开（公告）日：2015-10-22
The present invention is directed to heterocyclic compounds which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
[EN] 3-CARBAMOYL-1 -METHYLPYRIDINIUM NITRITE, PROCESS FOR ITS PREPARATION AND ITS USE<br/>[FR] NITRITE DE 3-CARBAMOYL-1-MÉTHYLPYRIDINIUM, PROCÉDÉ POUR SA PRÉPARATION ET SON UTILISATION
申请人：UNIV JAGIELLOŃSKI
公开号：WO2014200373A1
公开（公告）日：2014-12-18
The invention relates to a novel pyridinium salt comprising an anion in the form of a nitrite and a cation in the form of a 3-carbamoyl-l -methylpyridinium, the process of its preparation and its use for the manufacture of a vascular protective agent for the treatment or prevention of conditions or diseases associated with the dysfunction of vascular endothelium, failure of endothelial synthesis of nitric oxide (NO) and/or failure of endothelial synthesis of prostacyclin (PGI2).
Imination of<i>N</i>-methylpyridinium salts by liquid ammonia-potassium permanganate. A new synthesis of nudiflorine
作者：D. J. Buurman、H. C. van der Plas
DOI：10.1002/jhet.5570230409
日期：1986.7
Reaction of substituted 1-methyl(benzyl)pyridinium salts (1) with liquidammonia/potassiumpermanganate leads to introduction of the imino group at the carbon adjacent to the nitrogen. The regiospecificity of the reaction strongly depends on substituent X: at C-6 for X = H, CONH2, C6H5 and at C-2 for X = CH3. 3-Aminocarbonyl-1-t-butylpyridinium iodide (5) on treatment with liquidammonia/potassium
取代的1-甲基（苄基）吡啶鎓盐（1）与液态氨/高锰酸钾的反应导致在与氮相邻的碳上引入亚氨基。该反应的区域特异性强烈取决于取代基X：对于C ＝ 6，对于X ＝ H，CONH 2，C 6 H 5，对于C ＝ 2，对于X ＝ CH 3。用液氨/高锰酸钾处理的3-氨基羰基-1-叔丁基碘化碘化物（5）仅得到4-亚氨基化合物8 ; 1 H nmr光谱显示5在液氨中，得到σ-加合物4-氨基-1,4-二氢-和6-氨基-1,6-二氢-3-吡啶甲酰胺的混合物（6和7）。令人惊讶地，在用液态氨/高锰酸钾，1，6-二氢-1-甲基-6-氧代-3-吡啶甲酰胺（14）处理3-氨基羰基-1,6-二甲基吡啶碘化物（13）时观察到了氧十二烷基甲基化反应。被获得。该化合物可以很容易地被三氯氧化磷转化为生物碱nudiflorine（15）。
