(2S)-2-氨基-6-[2-[[(4S)-4-氨基-5-羟基-5-氧代戊基]氨基]咪唑并[4,5-b]吡啶-4-基]己酸 | 124505-87-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (2S)-2-氨基-6-[2-[[(4S)-4-氨基-5-羟基-5-氧代戊基]氨基]咪唑并[4,5-b]吡啶-4-基]己酸
• 英文名称: Pentosidine
• 英文别名: (2S)-2-amino-6-[2-[[(4S)-4-amino-4-carboxybutyl]amino]imidazo[4,5-b]pyridin-4-yl]hexanoic acid
• CAS: 124505-87-9
• 化学式: C₁₇H₂₆N₆O₄
• 分子量: 378.4
• InChiKey: AYEKKSTZQYEZPU-RYUDHWBXSA-N

物化性质

• 沸点：
  655.6±65.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：21.4mg/mL； DMSO：22.4mg/mL；乙醇：31.3mg/mL； PBS（pH 7.2）：10 mg/mL
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  169
• 氢给体数：
  5
• 氢受体数：
  9

ADMET

代谢

尿素毒素往往会因为饮食过量或者肾脏过滤功能不佳而在血液中积聚。大多数尿素毒素是代谢废物，通常通过尿液或粪便排出。

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.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

尿毒症毒素如戊糖素通过有机离子转运体（特别是OAT3）被积极运输到肾脏中。尿毒症毒素水平的增加可以刺激活性氧种类的产生。这似乎是通过尿毒症毒素直接结合或抑制NADPH氧化酶（特别是肾脏和心脏中丰富的NOX4）来介导的（A7868）。活性氧种类可以诱导几种不同的DNA甲基转移酶（DNMTs），这些酶参与沉默一种名为KLOTHO的蛋白质。KLOTHO已被确定在抗衰老、矿物质代谢和维生素D代谢中具有重要作用。许多研究表明，在急性或慢性肾脏疾病中，由于局部活性氧种类水平升高，KLOTHO mRNA和蛋白质水平会降低（A7869）。

Uremic toxins such as pentosidine 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

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

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.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

内源性的，摄入，皮肤（接触）

Endogenous, Ingestion, Dermal (contact)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

作为尿毒症毒素，这种化合物可以引起尿毒症综合征。尿毒症综合征可能影响身体的任何部位，并可能导致恶心、呕吐、食欲丧失和体重减轻。它还可能引起精神状态的变化，如混乱、意识减退、躁动、精神疾病、癫痫和昏迷。还可能出现异常出血，例如在非常轻微的损伤后自发或大量出血。心脏问题，如心律不齐、心脏包膜（心包炎）炎症和心脏压力增加，也可能出现在尿毒症综合征患者身上。由于肺部和胸壁之间（胸腔积液）的液体积聚导致的呼吸急促也可能出现。

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.

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为产物：
  描述：

  L-精氨酸 、 L-赖氨酸 、 D-核糖 在 水 、 吡啶 、 (2S)-2-氨基-6-[2-[[(4S)-4-氨基-5-羟基-5-氧代戊基]氨基]咪唑并[4,5-b]吡啶-4-基]己酸 、 sodium hydroxide 作用下， 反应 1.0h， 生成 (2S)-2-氨基-6-[2-[[(4S)-4-氨基-5-羟基-5-氧代戊基]氨基]咪唑并[4,5-b]吡啶-4-基]己酸
  参考文献：
  名称：

  Process for assessing the biological age of a tissue

  摘要：

  本发明涉及使用由赖氨酸和精氨酸残基交联的一种嘧啶并[4,5b]吡啶分子，该分子由戊糖糖基组成，用于评估组织的生物年龄。

  公开号：

  US05480807A1
• 作为试剂：
  描述：

  L-精氨酸 、 L-赖氨酸 、 D-核糖 在 水 、 吡啶 、 (2S)-2-氨基-6-[2-[[(4S)-4-氨基-5-羟基-5-氧代戊基]氨基]咪唑并[4,5-b]吡啶-4-基]己酸 、 sodium hydroxide 作用下， 反应 1.0h， 生成 (2S)-2-氨基-6-[2-[[(4S)-4-氨基-5-羟基-5-氧代戊基]氨基]咪唑并[4,5-b]吡啶-4-基]己酸
  参考文献：
  名称：

  Imidazopyridinium compound and processes for isolating, identifying, and

  摘要：

  本发明涉及一种新型咪唑[4,5b]吡啶分子，由赖氨酸和精氨酸残基与戊糖糖交联组成。这种新型咪唑[4,5b]吡啶化合物称为“戊糖氨基酸”，从经历了高级糖基化的蛋白质组织中分离出来，被认为是非酶促褐变和/或蛋白质老化中涉及的主要产物之一。检测戊糖氨基酸分子可以评估蛋白质老化的程度，这是由戊糖诱导的交联介导的，并受糖尿病和肾病等疾病的调节。此外，通过生产单克隆抗体和/或制备诊断试剂盒等，可以利用戊糖氨基酸分子进行诊断和治疗（即开发抑制非酶促褐变反应等药物）。

  公开号：

  US05214138A1

文献信息

• Crosslink Breakers for Preservation of Biological Substances
  申请人：Spiegel David

  公开号：US20150099260A1

  公开（公告）日：2015-04-09

  A preservative for body fluids, proteins, cells and tissues comprising an effective amount of an AGE crosslink breaker for preventing formation of advanced glycation end products. The AGE crosslink breaker comprises a compound of Structure (1): wherein V, W, X, Y and Z are any atom suitable for a heterocyclic carbene or carbene precursor framework, including B, C, O, N, S, Se, P, and As in any chemically-feasible oxidation state; wherein Q, R, M, T and U are any atom or substituent, including but not limited to, H, CL n , NL n , PL n , OL n , SL n , SeL n , L n Cl, L n Br, L n I, wherein L is any atom, substituent or group, and n is any integer such that Q, R, M, T, and U can access all chemically-feasible oxidation states; and wherein G comprises any charged counter ion including, but not limited to those derived from C, O, N, B, Al, S, Se, Cl, Br, I in any chemically-feasible oxidation state.

  一种用于体液、蛋白质、细胞和组织的防腐剂，包括一种有效量的AGE交联断裂剂，用于预防高级糖基化终产物的形成。AGE交联断裂剂包括结构（1）中的化合物： 其中V、W、X、Y和Z是适用于杂环卡宾或卡宾前体框架的任何原子，包括B、C、O、N、S、Se、P和As在任何化学上可行的氧化态； 其中Q、R、M、T和U是任何原子或取代基，包括但不限于H、CLn、NLn、PLn、OLn、SLn、SeLn、LnCl、LnBr、LnI，其中L是任何原子、取代基或基团，n是任何整数，使得Q、R、M、T和U可以访问所有化学上可行的氧化态；以及 其中G包括任何带电的对离子，包括但不限于那些来源于C、O、N、B、Al、S、Se、Cl、Br、I在任何化学上可行的氧化态。
• SUBSTITUTED 2,4 DIAMINO-QUINOLINE AS NEW MEDICAMENT FOR FIBROSIS, AUTOPHAGY AND CATHEPSINS B (CTSB), L (CTSL) AND D (CTSD) RELATED DISEASES
  申请人：Genoscience Pharma SAS

  公开号：EP3620164A1

  公开（公告）日：2020-03-11

  The present invention relates to novel 2-primary amino-4-secondary amino-quinoline derivatives, their manufacture, pharmaceutical compositions comprising them and their use as medicaments. The active compounds of the present invention can be useful as a medicament in the treatment and/or the decreasing and/or the prevention of fibrosis and/or fibrosis related diseases, or for use as a medicament in the treatment and/or the decreasing and/or the prevention of the autophagy and/or autophagy related diseases and for the inhibition of the autophagy flux, or for use in the inhibition of cathepsins B (CTSB), L (CTSL) and/or D (CTSD) and/or cathepsins B (CTSB), L (CTSL) and/or D (CTSD) related diseases; with the proviso that said compounds are not to be used for the treatment of any forms of cancers.

  本发明涉及新型2-初级氨基-4-次级氨基喹啉衍生物，其制备方法，包含它们的药物组合物以及它们作为药物的用途。本发明的活性化合物可用作药物治疗和/或减少和/或预防纤维化和/或与纤维化相关疾病，或用作药物治疗和/或减少和/或预防自噬和/或与自噬相关疾病以及抑制自噬通量，或用于抑制蛋白酶B（CTSB）、L（CTSL）和/或D（CTSD）和/或与蛋白酶B（CTSB）、L（CTSL）和/或D（CTSD）相关疾病；但所述化合物不得用于治疗任何形式的癌症。
• AMINO ACID AMIDES OF PHENOXYBUTYRIC ACID DERIVATIVES
  申请人：LALEZARI IRAJ

  公开号：US20120232120A1

  公开（公告）日：2012-09-13

  A compound of the formula: where X is phenyl substituted at the 3, 4 and 5 positions with R1, R2 or R3 which are selected from hydrogen, chloro, lower alkyl of 1 to 5 carbons, phenoxy, phenyl, naphthyl, or phenyl (lower) alkyl where the lower alkyl group has 1-5 carbon atoms and m is 0 or 1; Y is —CONH— or —NHCONH— where the nitrogen atoms are unsubstituted or substituted with other phenoxyisobutyric acid derivatives, or the residue of a phenoxyisobutyric acid and n is 0 or 1; Z is unsubstituted phenyl when m is 1 and n is 1; when Y is 0, X is 0; Z is also substituted.

  式的化合物： 其中X是苯基，取代在3、4和5位与R1、R2或R3，它们从氢、氯、1至5个碳原子的低烷基、苯氧基、苯基、萘基或苯基（低）烷基中选择，其中低烷基基团有1-5个碳原子，m为0或1；Y为—CONH—或—NHCONH—，其中氮原子未取代或取代为其他苯氧异丁酸衍生物，或苯氧异丁酸的残基，n为0或1；当m为1且n为1时，Z为未取代的苯基；当Y为0时，X为0；Z也被取代。
• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF RENAL DISEASES<br/>[FR] COMPOSITIONS ET MÉTHODES POUR LE TRAITEMENT DE NÉPHROPATHIES
  申请人：MOHAN M ALAPATI

  公开号：WO2016046670A1

  公开（公告）日：2016-03-31

  The compositions and compounds of formula I which includes a salt of pyridoxamine or its polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for oral administration, delayed release or sustained release, transmucosal, syrup, topical, parenteral administration, injection, subdermal, oral solution, rectal administration, nanoparticle, buccal administration or transdermal administration. Such compositions may be used to treatment of kidney disease, diabetic renal diseases, chronic kidney disease, albuminuria, or its associated complications.

  公式I的组合物和化合物包括吡啶醇盐或其多晶形、对映体、立体异构体、溶剂合物和水合物。这些盐可以制成药物组合物。药物组合物可以制成口服、延迟释放或持续释放、经粘膜、糖浆、局部、肠道、注射、皮下、口服溶液、直肠给药、纳米颗粒、颊黏膜给药或经皮给药的制剂。这些组合物可用于治疗肾脏疾病、糖尿病肾病、慢性肾脏疾病、白蛋白尿或其相关并发症。
• Novel breakers of advanced glycation endproducts
  申请人：City of Hope

  公开号：US20020002203A1

  公开（公告）日：2002-01-03

  Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of a variety of debilitating diseases such as diabetes, atherosclerosis, Alzheimer's and rheumatoid arthritis, as well as in the normal aging process. Seven compounds are here reported to be active in breaking AGE-protein cross-links. These compounds are 1,4-benzene-bis[4-methyleneaminophenoxyisobutyric acid] (LR102); 4-[(3,5-dichlorophenylureidophenoxyisobutyryl]-4-aminobenzoic acid (LR99); L-bis-[4-(4-chlorobenzamidophenoxyisobutyryl)cystine] (LR20); 4-(3,5-dichlorophenylureido)phenoxyisobutyryl-1-amidocyclohexane-1-carboxylic acid (LR23); methylene bis [4,4′-(2-chlorophenylureidophenoxyisobutyric acid)] (LR90); 5-aminosalicylic acid (5-ASA); and metformin. These compounds may be used to reverse the debilitating effects of those diseases in which AGEs are formed.

  AGEs已被指称与多种令人痛苦的疾病的发病机制有关，如糖尿病、动脉粥样硬化、阿尔茨海默病和类风湿性关节炎，以及正常衰老过程。这里报道了七种化合物能够活跃地破坏AGE-蛋白交联。这些化合物分别是1,4-苯二[4-亚甲基氨基苯氧异丁酸]（LR102）；4-[(3,5-二氯苯脲基苯氧异丁酰]-4-氨基苯甲酸（LR99）；L-双-[4-(4-氯苯酰胺基苯氧异丁酰)半胱氨酸]（LR20）；4-(3,5-二氯苯脲基)苯氧异丁酰-1-氨基环己烷-1-羧酸（LR23）；亚甲基双 [4,4′-(2-氯苯脲基苯氧异丁酸)]（LR90）；5-氨基水杨酸（5-ASA）；和二甲双胍。这些化合物可用于逆转那些形成AGEs的疾病的令人痛苦影响。