6-{[[(叔丁氧基)羰基]氨基}螺[3.3]庚烷-2-羧酸甲酯 | 170508-14-2

• 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: 6-{[[(叔丁氧基)羰基]氨基}螺[3.3]庚烷-2-羧酸甲酯
• 英文名称: methyl 6-((tert-butoxycarbonyl)amino)spiro[3.3]heptane-2-carboxylate
• 英文别名: methyl 6-(Boc-amino)spiro[3.3]heptane-2-carboxylate；methyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]spiro[3.3]heptane-6-carboxylate
• CAS: 170508-14-2
• 化学式: C₁₄H₂₃NO₄
• 分子量: 269.341
• InChiKey: QUQKSJIPMWXDSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-{[[(叔丁氧基)羰基]氨基}螺[3.3]庚烷-2-羧酸甲酯 在 甲醇 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (+/-)-2-hydroxymethyl-6-<(N-tert-butoxycarbonyl)amino>spiro<3.3>heptane
  参考文献：
  名称：

  [EN] ANTI-HUMAN VISTA ANTIBODIES AND USE THEREOF
  [FR] ANTICORPS ANTI-VISTA HUMAINS ET UTILISATION ASSOCIÉE

  摘要：

  本发明提供了抗VISTA抗体药物偶联物，可用于针对免疫细胞（例如，髓系细胞）的靶向递送抗炎剂，例如类固醇。本发明还提供了在治疗炎症和/或自身免疫状况以及/或减轻抗炎剂（如类固醇）的毒性中使用抗VISTA抗体药物偶联物的方法。

  公开号：

  WO2021216913A1
• 作为产物：
  描述：

  6-(甲氧基羰基)螺[3.3]庚烷-2-羧酸 在 lead(IV) acetate 、 氨 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.84h， 生成 6-{[[(叔丁氧基)羰基]氨基}螺[3.3]庚烷-2-羧酸甲酯
  参考文献：
  名称：

  (.+-.)-N9-(2-(Hydroxymethyl)spiro[3.3]hept-6-yl)adenine. The First Biologically Active Saturated Analog of Adenallene with Axial Dissymmetry

  摘要：

  Synthesis of the title analogue 2 is described. Fecht's acid (3) was esterified with N,N-dimethylformamide dimethyl acetal to give monoester 4 along with diester 5. Compound 4 was transformed to ester amide 6 by the reaction with isobutyl chloroformate and triethylamine followed by ammonolysis. Hoffman rearrangement of 6 effected by lead tetraacetate in tert-butyl alcohol led to the N-tert-butoxycarbonyl ester 7. The latter was reduced with Ca(BH4)(2) to give the protected amino alcohol 8. Removal of the N-tert-butoxycarbonyl group with 2 M HCl in methanol afforded the hydrochloride of amino alcohol 9. Reaction of 9 with 5-amino-4,6-dichloropyrimidine and triethylamine gave the pyrimidine derivative 10 which, in turn, was cyclized to 6-chloropurine 11a. Ammonolysis of the latter intermediate afforded the title analogue 2. The H-1 NMR spectrum of Fecht's acid (3) in CD3COCD3 showed that four methylene protons were magnetically nonequivalent (two quartets) whereas the other four were equivalent, forming a single doublet. Compound 2 inhibited the replication of human cytomegalovirus (IC50 32 mu M) and growth of murine leukemia L1210 cells (IC50 30 mu M). Zone assays showed inhibition of the following tumor cultures at 0.5 mg/disk: murine leukemia P388, mouse tumors PO3, C38, and M17/Adr as well as human tumors MCF-7 and CX-1..

  DOI：

  10.1021/jo00125a011

文献信息

• [EN] 1,3 DI-SUBSTITUTED CYCLOBUTANE OR AZETIDINE DERIVATIVES AS HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE INHIBITORS<br/>[FR] DÉRIVÉS D'AZÉTIDINE OU DE CYCLOBUTANE 1,3-DISUBSTITUÉS UTILISÉS COMME INHIBITEURS DE LA PROSTAGLANDINE D SYNTHASE HÉMATOPOÏÉTIQUE (H-PGDS)
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018069863A1

  公开（公告）日：2018-04-19

  A compound of formula (I), wherein R, R1, R2, R3, Y, Y1, a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  式（I）的化合物，其中R、R1、R2、R3、Y、Y1、a、X和Z的定义如本文所述。本发明的化合物是造血前列腺素D合成酶（H-PGDS）的抑制剂，可用于治疗杜兴氏肌肉萎缩症。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物来抑制H-PGDS活性和治疗相关疾病的方法。
• BICYCLIC CARBOXAMIDES AND METHODS OF USE THEREOF
  申请人：Tempest Therapeutics, Inc.

  公开号：US20190315712A1

  公开（公告）日：2019-10-17

  Compounds, compositions and methods are provided for modulating the activity of EP 2 and EP 4 receptors, and for the treatment, prevention and amelioration of one or more symptoms of diseases or disorders related to the activity of EP 2 and EP 4 receptors. In certain embodiments, the compounds are antagonists of both the EP 2 and EP 4 receptors.

  提供了用于调节EP2和EP4受体活性的化合物、组合物和方法，以及用于治疗、预防和改善与EP2和EP4受体活性相关的疾病或疾病症状的一种或多种方法。在某些实施例中，这些化合物是EP2和EP4受体的拮抗剂。
• [EN] ANTI-HUMAN VISTA ANTIBODIES AND USE THEREOF<br/>[FR] ANTICORPS ANTI-VISTA HUMAINS ET UTILISATION ASSOCIÉE
  申请人：IMMUNEXT INC

  公开号：WO2021216913A1

  公开（公告）日：2021-10-28

  The invention provides anti-VISTA antibody drug conjugates which may be used for targeted delivery of anti-inflammatory agents such as steroids to immune cells, e.g., myeloid cells. The invention also provides methods of using anti-VISTA antibody drug conjugates in the treatment of inflammatory and/or autoimmune conditions and/or for alleviating the toxicity of anti-inflammatory agents such as steroids.

  本发明提供了抗VISTA抗体药物偶联物，可用于针对免疫细胞（例如，髓系细胞）的靶向递送抗炎剂，例如类固醇。本发明还提供了在治疗炎症和/或自身免疫状况以及/或减轻抗炎剂（如类固醇）的毒性中使用抗VISTA抗体药物偶联物的方法。
• Cyclobutane-Derived Diamines: Synthesis and Molecular Structure
  作者：Dmytro S. Radchenko、Sergiy O. Pavlenko、Oleksandr O. Grygorenko、Dmitriy M. Volochnyuk、Svitlana V. Shishkina、Oleg V. Shishkin、Igor V. Komarov

  DOI：10.1021/jo101271h

  日期：2010.9.3

  Cyclobutane diamines (i.e., cis- and trans-1,3-diaminocyclobutane, 6-amino-3-azaspiro[3.3]heptane, and 3,6-diaminospiro[3.3]heptane) are considered as promising sterically constrained diamine building blocks for drug discovery. An approach to the syntheses of their Boc-monoprotected derivatives has been developed aimed at the preparation of multigram amounts of the compounds. These novel synthetic

  环丁烷二胺（即顺式和反式-1,3-二氨基环丁烷，6-氨基-3-氮杂螺[3.3]庚烷和3,6-二氨基螺[3.3]庚烷）被认为是有前途的受空间约束的二胺结构药物发现。已经开发了合成其Boc单保护衍生物的方法，旨在制备多克量的化合物。这些新颖的合成方案利用经典的丙二酸酯烷基化化学方法来构建环丁烷环。环丁烷二胺衍生物的构象偏好已通过X射线衍射进行了评估，并与空间受限的二胺的文献数据进行了比较，后者是市售药物的组成部分。
• [EN] NOVEL COMPOUNDS HAVING INHIBITORY ACTIVITY ON PROSTAGLANDIN E2 RECEPTOR AND USES THEREOF<br/>[FR] NOUVEAUX COMPOSÉS AYANT UNE ACTIVITÉ INHIBITRICE SUR LE RÉCEPTEUR DE LA PROSTAGLANDINE E2 ET LEURS UTILISATIONS
  申请人：KANAPH THERAPEUTICS INC

  公开号：WO2022039563A1

  公开（公告）日：2022-02-24

  The present application relates to a novel compound having inhibitory activity on prostaglandin E2 receptor and uses thereof, and provides a compound represented by formula I, a solvate, stereoisomer or pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same, and a method of using the same.

  本申请涉及一种对前列腺素E2受体具有抑制活性的新化合物及其用途，提供了一种由式I代表的化合物，其溶剂化物、立体异构体或药用可接受的盐，包括该化合物的药物组合物，以及使用该化合物的方法。