6-叔丁基-7,8-二氢-1,6-萘啶-2,6(5H)-二羧酸-2-甲酯 | 259809-47-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 6-叔丁基-7,8-二氢-1,6-萘啶-2,6(5H)-二羧酸-2-甲酯
• 中文别名: 6-叔-丁基2-甲基7,8-二氢-1,6-萘啶-2,6(5H)-二甲酸基酯
• 英文名称: 6-(tert-butoxycarbonyl)-2-methoxycarbonyl-5,6,7,8-tetrahydro-1,6-naphthyridine
• 英文别名: O6-tert-butyl O2-methyl 7,8-dihydro-5H-1,6-naphthyridine-2,6-dicarboxylate；6-tert-butyl 2-methyl 7,8-dihydro-5H-1,6-naphthyridine-2,6-dicarboxylate；6-(1,1-dimethylethyl)-2-methyl-7,8-dihydro-1,6-naphthyridine-2,6(5H)-dicarboxylate；6-tert-butyl 2-methyl 7,8-dihydro-1,6-naphthyridine-2,6(5H)-dicarboxylate；6-O-tert-butyl 2-O-methyl 7,8-dihydro-5H-1,6-naphthyridine-2,6-dicarboxylate
• CAS: 259809-47-7
• 化学式: C₁₅H₂₀N₂O₄
• 分子量: 292.335
• InChiKey: SIDSQSLFPRZTOG-UHFFFAOYSA-N

物化性质

• 沸点：
  432.9±45.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-叔丁基-7,8-二氢-1,6-萘啶-2,6(5H)-二羧酸-2-甲酯 在 二异丁基氢化铝 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以320 mg的产率得到tert-butyl 2-(hydroxymethyl)-7,8-dihydro-5H-1,6-naphthyridine-6-carboxylate
  参考文献：
  名称：

  [EN] PIPERIDINYL AMINE COMPOUNDS FOR THE TREATMENT OF AUTOIMMUNE DISEASE
  [FR] COMPOSÉS DE PIPÉRIDINYL AMINE POUR LE TRAITEMENT D'UNE MALADIE AUTO-IMMUNE

  摘要：

  本发明涉及公式（I）的化合物，其中R1、R2、R3、R4和R5如本文所述，并且它们的药用盐、对映体或二对映体，以及包括该化合物的组合物和使用该化合物的方法。

  公开号：

  WO2021052892A1
• 作为产物：
  描述：

  2-氰基-7,8-二氢-1,6-萘啶-6(5H)-羧酸叔丁酯 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.5h， 生成 6-叔丁基-7,8-二氢-1,6-萘啶-2,6(5H)-二羧酸-2-甲酯
  参考文献：
  名称：

  Synthesis and Conformational Analysis of a Non-Amidine Factor Xa Inhibitor That Incorporates 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 Binding Element

  摘要：

  Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.

  DOI：

  10.1021/jm049884d

文献信息

• [EN] SUBSTITUTE 1, 6-NAPHTHYRIDINES FOR USE AS SCD INHIBITORS<br/>[FR] 1,6-NAPHTYRIDINES SUBSTITUÉES EN VUE D'UNE UTILISATION EN TANT QU'INHIBITEURS DE SCD
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009056556A1

  公开（公告）日：2009-05-07

  The present invention relates to substituted tetrahydronaphthyridine (THN) compounds of the formula (I) and salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds for inhibiting SCD activity.

  本发明涉及公式（I）的取代四氢萘啶（THN）化合物及其盐，含有它们的药物组合物以及它们在医学上的用途。具体而言，该发明涉及用于抑制SCD活性的化合物。
• NOVEL SULFONYL DERIVATIVES
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1104754A1

  公开（公告）日：2001-06-06

  Sulfonyl derivatives represented by the following general formula (I): Q1-Q2-T1-Q3-SO2-QA and drugs containing the same (wherein Q1 is an optionally substituted, saturated or unsaturated, five- or six-membered cyclic hydrocarbon group, a five- or six-membered heterocyclic group, or the like; Q2 is a single band, oxygen, sulfur, C1-C6 alkylene or the like; QA is optionally substituted arylalkenyl, heteroarylalkenyl or the like; and T1 is carbonyl or the like). These compounds have potent FXa-inhibitory effects and promptly exert satisfactory and persistent antithrombotic effects through oral administration, thus being useful as anticoagulant agents little accompanied with side effects.

  以下是通用公式（I）所代表的磺酰衍生物：Q1-Q2-T1-Q3-SO2-QA以及含有这些衍生物的药物（其中Q1是可选择地取代的饱和或不饱和的五元或六元环烃基团，五元或六元杂环基团等；Q2是单键，氧，硫，C1-C6烷基或类似物；QA是可选择地取代的芳基烯烃基团，杂环芳基烯烃基团或类似物；T1是羰基或类似物）。这些化合物具有强大的FXa抑制作用，并通过口服迅速产生令人满意且持久的抗血栓作用，因此可作为几乎不伴随副作用的抗凝血剂。
• HETEROCYCLIC CARBOXYLIC ACIDS AS ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20160024059A1

  公开（公告）日：2016-01-28

  The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , B, V, W, X, Y, Z and m are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及具有以下式I的化合物及其药学上可接受的盐，其中R1、R2、R3、R5、R6、R7、R8、R9、B、V、W、X、Y、Z和m如本文所定义。该发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和紊乱的方法，制备这些化合物的方法以及在这些过程中有用的中间体。
• [EN] PIPERIDINYL AMINE COMPOUNDS FOR THE TREATMENT OF AUTOIMMUNE DISEASE<br/>[FR] COMPOSÉS DE PIPÉRIDINYL AMINE POUR LE TRAITEMENT D'UNE MALADIE AUTO-IMMUNE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021052892A1

  公开（公告）日：2021-03-25

  The present invention relates to compounds of formula (I), wherein R1, R2, R3, R4 and R5 are as described herein, and their pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.

  本发明涉及公式（I）的化合物，其中R1、R2、R3、R4和R5如本文所述，并且它们的药用盐、对映体或二对映体，以及包括该化合物的组合物和使用该化合物的方法。
• DRUG COMPOSITIONS AND METHODS FOR PREVENTING AND TREATING THROMBOSIS OR EMBOLISM
  申请人：OHTA Toshiharu

  公开号：US20090281074A1

  公开（公告）日：2009-11-12

  Drug compositions containing a substituted diamine compound represented by formula (1): Q 1 -Q 2 -r-N(R 1 )-Q 3 -N(R 2 )  (1) wherein Q 3 represents the following group wherein Q 5 represents an alkylene group having 4 carbon atoms, R 3 represents a hydrogen atom, and R 4 represents a 3-6 membered heterocyclic group which may be substituted; are useful for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.

  含有以下式子（1）所代表的取代二胺化合物的药物组合物： Q1-Q2-r-N（R1）-Q3-N（R2）  （1） 其中，Q3代表以下基团： 其中，Q5代表具有4个碳原子的烷基基团，R3代表氢原子，R4代表可取代的3-6环杂环基团； 该药物组合物对于预防和/或治疗脑梗死、脑栓塞、心肌梗死、心绞痛、肺梗死、肺栓塞、布尔格病、深静脉血栓形成、弥散性血管内凝血综合征、人工瓣膜或关节置换后的血栓形成、血管成形术后的血栓形成和再闭塞、全身性炎症反应综合征（SIRS）、多器官功能障碍综合征（MODS）、体外循环期间的血栓形成或采血时的血凝。