L-isoleucinamide | 1225449-97-7

• 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
• 英文名称: L-isoleucinamide
• 英文别名: L-isoleucine amide；(2S)-2-amino-3-methylpentanamide
• CAS: 1225449-97-7
• 化学式: C₆H₁₄N₂O
• 分子量: 130.19
• InChiKey: JDAMFKGXSUOWBV-AKGZTFGVSA-N

物化性质

• 沸点：
  250.9±23.0 °C(Predicted)
• 密度：
  0.980±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  69.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  L-isoleucinamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 L-1,2-diamino-3-methylpentane
  参考文献：
  名称：

  Brunner; Schmidt; Unger, European Journal of Medicinal Chemistry, 1985, vol. 20, # 6, p. 509 - 512

  摘要：

  DOI：
• 作为产物：
  描述：

  isoleucine 在 氯化亚砜 、 氨 作用下， 以 甲醇 为溶剂， 反应 148.0h， 生成 L-isoleucinamide
  参考文献：
  名称：

  Brunner; Schmidt; Unger, European Journal of Medicinal Chemistry, 1985, vol. 20, # 6, p. 509 - 512

  摘要：

  DOI：

文献信息

• Novel tetrahydrocarbazole derivatives having improved biological action and improved solubility as ligands of G-protein coupled receptors (GPCRs)
  申请人：Paulini Klaus

  公开号：US20060014818A1

  公开（公告）日：2006-01-19

  The present invention provides novel tetrahydrocarbazole derivatives which have improved properties and which can be employed as inhibitors of GPCRs. This results in the possibility of using the novel compounds to treat pathological conditions whose severity depends on the pathobiochemical effect of GPCRs. The compounds of the invention act in particular via an antagonistic inhibition of the LHRH receptor. The invention further provides medicaments which comprise one or more of the novel compounds as active ingredient. The medicaments are suitable in particular to be employed in an oral dosage form for a mammal, in particular a human.

  本发明提供了新颖的四氢咔唑衍生物，具有改进的性能，并可用作GPCR的抑制剂。这导致可以利用这些新型化合物来治疗病理条件，其严重程度取决于GPCR的病理生物化学效应。本发明的化合物特别通过对LHRH受体的拮抗性抑制发挥作用。本发明还提供了包含一种或多种新型化合物作为活性成分的药物。这些药物特别适合用于口服剂型，用于哺乳动物，特别是人类。
• KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease
  作者：Min-Ho Nam、Jong-Hyun Park、Hyo Jung Song、Ji Won Choi、Siwon Kim、Bo Ko Jang、Hyung Ho Yoon、Jun Young Heo、Hyowon Lee、Heeyoung An、Hyeon Jeong Kim、Sun Jun Park、Doo-Wan Cho、Young-Su Yang、Su-Cheol Han、Sangwook Kim、Soo-Jin Oh、Sang Ryong Jeon、Ki Duk Park、C. Justin Lee

  DOI：10.1007/s13311-021-01097-4

  日期：2021.7

  Monoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD.

  单胺氧化酶-B（MAO-B）是帕金森病（PD）的一个被广泛认可的治疗靶点；然而，先前对目前可用的不可逆MAO-B抑制剂进行的临床研究显示出令人失望的神经保护效果。在这里，我们测试了KDS2010的治疗潜力，这是一种最近合成的强效、选择性和可逆的MAO-B抑制剂，在多个PD动物模型中进行了测试。我们设计并合成了一系列α-氨酰胺衍生物，并发现衍生物KDS2010表现出最高的效力、特异性、可逆性和生物利用度（> 100%）。此外，KDS2010在小鼠MPTP帕金森病模型中表现出显著的神经保护和抗神经炎症效果，对黑质纹状体通路的破坏具有显著作用。KDS2010治疗还缓解了6-羟基多巴胺诱导和A53T突变α-突触核蛋白过表达大鼠PD模型的帕金森病运动功能障碍。此外，KDS2010在非人灵长类动物中几乎没有毒性或副作用。KDS2010可能是PD的下一代治疗候选药物。
• Preparation and Characterization of (Amino carboxamidato-<i>N</i>,<i>N</i>′)(chloro)(dimethyl sulfoxide-<i>S</i>)platinum(II) Complexes
  作者：Takashi Komorita、Akira Fuyuhiro、Kazumi Tanimoto、Koji Yamauchi、Kazumi Fujita

  DOI：10.1246/bcsj.68.1593

  日期：1995.6

  13(3)°, Z = 2, and final R = 0.029 and RW = 0.034. The crystal of 3b was monoclinic, space group P21 with a = 7.158(2), b = 9.948(2), c = 8.741(2) A, β = 102.76(2)°, Z = 2, and final R = 0.041 and Rw = 0.050. Both complexes were found to contain a carboxamidato group coordinating to platinum(II) through the nitrogen atom. A larger trans influence was observed for the coordinating carboxamidato nitrogen

  制备了 [PtCl(aaa-N,N')(dmso-S)] 类型的几种方形平面配合物（aaa = 氨基酸酰胺，dmso = 二甲基亚砜）。顺式(NH2,S)-[PtCl(DL-alaa)(dmso)]·H2O (4) 和反式(NH2,S)-[PtCl(DL-vala)(dmso)] (3b) 的晶体和分子结构) 由 X 射线衍射测定（alaa = 丙氨酰胺，vala = valinamidate）。4的晶体为三斜晶系，空间群 a = 9.144(2), b = 9.172(3), c = 7.371(2) A, α = 109.41(2)°, β = 99.69(2)°, γ = 76.13(3)°，Z = 2，最终 R = 0.029 和 RW = 0.034。3b的晶体为单斜晶系，空间群P21，a = 7.158(2), b = 9.948(2), c = 8.741(2) A, β =
• Quinazoline derivatives useful in cancer treatment
  申请人：Mallams K. Alan

  公开号：US20070015774A1

  公开（公告）日：2007-01-18

  The present invention provides compounds of Formula I (wherein R 1 , R 2 , R 3 , L, and X are as defined herein). or a pharmaceutically acceptable salt, solvate or ester thereof. The present invention also provides compositions comprising these compounds that are useful for treating cellular proliferative diseases, disorders associated with activity of mutants of p53, or in causing apoptosis of cancer cells.

  本发明提供了式I的化合物（其中R1、R2、R3、L和X如本文所定义）。或其药用可接受的盐、溶剂或酯。本发明还提供了包含这些化合物的组合物，用于治疗细胞增殖性疾病、与p53突变体活性有关的疾病，或导致癌细胞凋亡。
• BENZIMIDAZOLONE DERIVATIVES
  申请人：Ando Kazuo

  公开号：US20090298811A1

  公开（公告）日：2009-12-03

  This invention relates to compounds and methods for the treatment of a condition mediated by CB1 receptor activity in a mammalian subject including a human, which comprises administering to a mammal in need of such treatment a therapeutically effective amount of the compound of formula (I) or pharmaceutically acceptable salts thereof, wherein: A, B, R 1 , R 2 and R 3 are each as described herein. These compounds are useful in the treatment of a condition mediated by CB2 receptor binding activity such as, but not limited to, inflammatory pain, nociceptive pain, neuropathic pain, fibromyalgia, chronic low back pain, visceral pain, acute cerebral ischemia, pain, chronic pain, acute pain, post herpetic neuralgia, neuropathies, neuralgia, diabetic neuropathy, HIV-related neuropathy, nerve injury, rheumatoid arthritic pain, osteoarthritic pain, back pain, cancer pain, dental pain, fibromyalgia, neuritis, sciatica, inflammation, neurodegenerative disease, spasticity, epilepsy, Tourette's syndrome, Parkinson's disease, neuroprotection, anxiety, cough, broncho constriction, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colitis, cerebrovascular ischemia, cachexia, nausea, emesis, chemotherapy-induced emesis, rheumatoid arthritis, asthma, Crohn's disease, ulcerative colitis, asthma, dermatitis, seasonal allergic rhinitis, gastroesophageal reflux disease (GERD), constipation, diarrhea, functional gastrointestinal disorder, cutaneous T cell lymphoma, multiple sclerosis, osteoarthritis, psoriasis, systemic lupus erythematosus, diabetes, glaucoma, osteoporosis, glomerulonephritis, renal ischemia, nephritis, hepatitis, cerebral stroke, vasodialation, hypertension, vasculitis, myocardial infarction, cerebral ischemia, reversible airway obstruction, adult respiratory disease syndrome, chronic obstructive pulmonary disease (COPD), cryptogenic fibrosing alveolitis and bronchitis.

  本发明涉及化合物和方法，用于治疗由CB1受体活性在哺乳动物主体中介导的疾病，包括人类，其包括向需要该治疗的哺乳动物施用化合物的治疗有效量的公式(I)或其药用可接受盐，其中：A、B、R1、R2和R3如本文所述。这些化合物在治疗由CB2受体结合活性介导的疾病中有用，如但不限于炎症性疼痛、伤害性疼痛、神经性疼痛、纤维肌痛、慢性腰痛、内脏疼痛、急性脑缺血、疼痛、慢性疼痛、急性疼痛、带状疱疹后神经痛、神经病、神经痛、糖尿病性神经病、艾滋病相关神经病、神经损伤、类风湿性关节炎疼痛、骨关节炎疼痛、背部疼痛、癌症疼痛、牙痛、纤维肌痛、神经炎、坐骨神经痛、炎症、神经退行性疾病、痉挛、癫痫、托瑞特综合征、帕金森病、神经保护、焦虑、咳嗽、支气管痉挛、肠易激综合征（IBS）、炎症性肠病（IBD）、结肠炎、脑血管缺血、虚弱、恶心、呕吐、化疗诱导呕吐、类风湿关节炎、哮喘、克罗恩病、溃疡性结肠炎、皮炎、季节性过敏性鼻炎、胃食管反流病（GERD）、便秘、腹泻、功能性胃肠障碍、皮肤T细胞淋巴瘤、多发性硬化症、骨关节炎、牛皮癣、系统性红斑狼疮、糖尿病、青光眼、骨质疏松症、肾小球肾炎、肾缺血、肾炎、肝炎、脑中风、血管扩张、高血压、血管炎、心肌梗死、脑缺血、可逆气道阻塞、成人呼吸系统疾病综合征、慢性阻塞性肺疾病（COPD）、隐源性纤维化肺泡炎和支气管炎。