乙基4-氨基-2,6-二氟苯甲酸酯 | 191469-36-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 乙基4-氨基-2,6-二氟苯甲酸酯
• 英文名称: ethyl 2,6-difluoro-4-aminobenzoate
• 英文别名: ethyl 4-amino-2,6-difluorobenzoate
• CAS: 191469-36-0
• 化学式: C₉H₉F₂NO₂
• 分子量: 201.173
• InChiKey: UNWQLHONIWEPMU-UHFFFAOYSA-N

物化性质

• 沸点：
  317.6±42.0 °C(Predicted)
• 密度：
  1.301±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  乙基4-氨基-2,6-二氟苯甲酸酯 在 4-二甲氨基吡啶 、 sodium hydroxide 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 AGN 194574
  参考文献：
  名称：

  高效视黄酸受体α-选择性拮抗剂的鉴定。

  摘要：

  描述了一系列新型视黄酸受体α（RARα）拮抗剂1-5的合成和类视黄醇受体的完整特征。这些化合物与RARα具有高亲和力，但在基因反式激活中完全没有活性。它们还是视黄酸（RA）诱导的RARα基因转录的有效和有效拮抗剂。相对于RARβ/γ，化合物1-5对RARα表现出不同程度的选择性，而化合物5在结合和功能拮抗试验中选择性最高。这些化合物将是描述RARα在发育和成年动物中的生理作用的宝贵工具，它们本身可能是与RARα相关的人类疾病的有用治疗剂。

  DOI：

  10.1021/jm9703911
• 作为产物：
  描述：

  2,4,6-三氟苯甲酸 在 palladium on activated charcoal 氯化亚砜 、 sodium azide 、 氢气 、 三乙胺 作用下， 以 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 78.5h， 生成 乙基4-氨基-2,6-二氟苯甲酸酯
  参考文献：
  名称：

  视黄酸受体α亚型特异性激动剂的鉴定。

  摘要：

  DOI：

  10.1021/jm9603532
• 作为试剂：
  描述：

  3-Methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene-2-carbonyl chloride 、 乙基4-氨基-2,6-二氟苯甲酸酯 在 乙基4-氨基-2,6-二氟苯甲酸酯 作用下， 以85的产率得到2,6-Difluoro-4-[(3-methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene-2-carbonyl)-amino]-benzoic acid ethyl ester
  参考文献：
  名称：

  Bioorg. Med. Chem. Lett. 2002, 12, 3145-3148

  摘要：

  DOI：

文献信息

• [EN] THERAPEUTIC ARYL-AM I DO-ARYL COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS ARYLAMIDOARYLIQUES THÉRAPEUTIQUES ET LEUR UTILISATION
  申请人：KING S COLLEGE LONDON

  公开号：WO2011027106A1

  公开（公告）日：2011-03-10

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as "AAA compounds"), which, inter alia, are (selective) retinoic acid receptor α (RARα) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARα, and in the treatment of diseases and conditions that are mediated by RARα, that are ameliorated by the activation of RARα, etc., including cognitive disorders, memory impairment, memory deficit, senile dementia, Alzheimer's disease, early stage Alzheimer's disease, intermediate stage Alzheimer's disease, late stage Alzheimer's disease, cognitive impairment, and mild cognitive impairment.

  本发明一般涉及治疗化合物领域，更具体地涉及以下结构的某些芳基酰胺-芳基化合物（为方便起见，统称为“AAA化合物”），这些化合物是（选择性的）视黄酸受体α（RARα）激动剂。本发明还涉及包含这种化合物的药物组合物，以及利用这种化合物和组合物在体内外（选择性地）激活RARα，并用于治疗由RARα介导的疾病和症状，通过激活RARα得到改善等方面，包括认知障碍、记忆障碍、记忆缺陷、老年痴呆症、阿尔茨海默病、早期阿尔茨海默病、中期阿尔茨海默病、晚期阿尔茨海默病、认知障碍和轻度认知障碍的治疗。
• Therapeutic Aryl-Amido-Aryl Compounds and Their Use
  申请人：Corcoran Jonathan Patrick Thomas

  公开号：US20120149737A1

  公开（公告）日：2012-06-14

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as “AAA compounds”), which, inter alia, are (selective) retinoic acid receptor α (RARα) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARα, and in the treatment of diseases and conditions that are mediated by RARα, that are ameliorated by the activation of RARα, etc., including cognitive disorders, memory impairment, memory deficit, senile dementia, Alzheimer's disease, early stage Alzheimer's disease, intermediate stage Alzheimer's disease, late stage Alzheimer's disease, cognitive impairment, and mild cognitive impairment.

  本发明涉及治疗化合物领域，更具体地涉及以下公式的某些芳基酰胺-芳基化合物（为方便起见，以下统称为“AAA化合物”），其为（选择性）视黄酸受体α（RARα）激动剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在体外和体内（选择性地）激活RARα，并用于治疗由RARα介导的疾病和症状，以及通过激活RARα改善的疾病和症状，包括认知障碍、记忆障碍、记忆缺陷、老年性痴呆、阿尔茨海默病、早期阿尔茨海默病、中期阿尔茨海默病、晚期阿尔茨海默病、认知损害和轻度认知损害。
• GPR119 작용 활성을 갖는 신규 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 약제학적 조성물
  申请人：DONG-A ST CO., LTD. 동아에스티 주식회사(120130140418) Corp. No ▼ 110111-5079713BRN ▼204-86-40122

  公开号：KR20150018916A

  公开（公告）日：2015-02-25

  본 발명은 GPR119 작용 활성을 갖는 신규 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 약제학적 조성물에 관한 것이다. 보다 상세하게는 효과적인 혈당강하작용 및 췌장베타세포에 대한 긍정적 효과를 지니면서 만성 심혈관계 위험인자인 지질대사를 개선시켜 당뇨병과 같은 대사성 질환의 치료 및/또는 예방용 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 약제학적 조성물에 관한 것이다.

  本发明涉及具有GPR119作用活性的新化合物，其制备方法以及包含其作为有效成分的药学组合物。更详细地说，本发明涉及改善脂质代谢，具有有效降血糖作用和对胰岛β细胞产生积极影响的化合物，用于治疗和/或预防代谢性疾病，如糖尿病等慢性心血管危险因素的药物学组合物的制备方法及包含其作为有效成分的药学组合物。
• Synthesis and use of retinoid compounds having negative hormone and/or
  申请人：Allergan Sales, Inc.

  公开号：US05877207A1

  公开（公告）日：1999-03-02

  Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.

  含有芳基取代和芳基以及(3-氧代-1-丙烯基)-取代的苯并吡喃、苯并硫吡喃、1,2-二氢喹啉和5,6-二氢萘衍生物具有维甲酸负性激素和/或拮抗剂样生物活性。发明的RAR拮抗剂可用于哺乳动物，包括人类，以防止或减少RAR激动剂对结合受体位点的作用。具体而言，RAR激动剂与维甲酸药物一起给哺乳动物，以防止或改善维甲酸或维生素A或维生素A前体引起的毒性或副作用。维甲酸负性激素可用于增强其他维甲酸类和核受体激动剂的活性。例如，名为AGN 193109的维甲酸负性激素在体外转录激活实验中有效增加了其他维甲酸类和类固醇激素的有效性。此外，转录激活实验可用于鉴定具有负性激素活性的化合物。这些实验基于负性激素下调具有构成转录激活子域的嵌合维甲酸受体的活性的能力。
• 5-MEMBERED HETEROCYCLIC COMPOUND
  申请人：Muratake Hideaki

  公开号：US20110213156A1

  公开（公告）日：2011-09-01

  A compound represented by the following general formula (I): [wherein R 1 and R 2 represent an alkyl group, X represents —S—, —O— or —NH—, Y represents C or N, R 3 represents hydrogen atom or a C 1-10 alkyl group, Z represents —CO—N(R 5 )— (R 5 represents hydrogen atom or a C 1-6 alkyl group) or —C(R 6 )═C(R 7 )—CO—NH— (R 6 and R 7 represent hydrogen atom or a C 1-6 alkyl group), Ar represents an aryldiyl group or a heteroaryldiyl group, and R 4 represents —COOH, —OCH 2 —COOH, —CH 2 —COOH, or —CH 2 —CH 2 —COOH], which has a retinoid action and is useful as an active ingredient of a medicament.

  以下是通用式(I)所代表的化合物：[其中R1和R2代表烷基，X代表—S—、—O—或—NH—，Y代表C或N，R3代表氢原子或C1-10烷基，Z代表—CO—N(R5)—(R5代表氢原子或C1-6烷基)或—C(R6)═C(R7)—CO—NH—(R6和R7代表氢原子或C1-6烷基)，Ar代表芳基二基团或杂芳基二基团，R4代表—COOH、—OCH2—COOH、—CH2—COOH或—CH2—CH2—COOH]，具有视黄醇作用，是药物的有效成分。