(3,3-二氟环丁基)甲基胺 | 1159882-59-3

• 物质功能分类: 有机原料 - 氨基化合物 - 环烷胺、芳香单胺、芳香多胺及其衍生物和盐
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 有机氟化物
• 中文名称: (3,3-二氟环丁基)甲基胺
• 英文名称: (3,3-difluorocyclobutyl)methanamine
• 英文别名: 1-(3,3-difluorocyclobutyl)methanamine；3,3-difluorocyclobutylmethylamine
• CAS: 1159882-59-3
• 化学式: C₅H₉F₂N
• mdl: MFCD16036683
• 分子量: 121.13
• InChiKey: BUVXADKKXYLSTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3,3-二氟环丁基)甲基胺 在 溶剂黄146 、 1-丙基磷酸酐 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 36.0h， 生成
  参考文献：
  名称：

  Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides

  摘要：

  Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(35,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate.

  DOI：

  10.1021/acs.jmedchem.6b00752
• 作为产物：
  描述：

  3,3-二氟环丁烷甲腈 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 (3,3-二氟环丁基)甲基胺
  参考文献：
  名称：

  [EN] ISOINDOLINE DERIVATIVES COMPRISING PHENYL GROUPS AND THEIR USE IN THE TREATMENT OF PAIN DISORDERS
  [FR] DÉRIVÉS ISOINDOLINE COMPRENANT DES GROUPES PHÉNYLES ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES DE LA DOULEUR

  摘要：

  公式I的化合物被要求，其中R1是氢，C1-3烷基，Ci_3烷氧基，氰基，羟基或卤素基；其中所述Ci^烷基可以选择性地被一个或多个取代基独立地选择自羟基，Ci^烷氧基和氟基；所述Ci^烷氧基可以选择性地被一个或多个氟基取代；m为1或2；R2和R3分别且独立地选择自氢，Ci_4卤代烷基，Ci_4卤代烷氧基，卤素，Ci_4烷氧基，Ci_4烷基和C3_7环烷氧基；其中所述C3. γ环烷氧基可以选择性地被一个或多个氟基取代；且R2和R3不能同时为氢；D为C3_7环烷基或C3_7杂环烷基；其中所述Cs-j环烷基或Cs-γ杂环烷基可以选择性地被一个或多个X*取代；X4为卤素，Ci_3烷基，Ci_3烷基0Ci_3烷基，Ci_3烷氧基，苄基，Ci_4烷基磺酰基，氧代，R4O(C=O)，R5(C=O)，或C5.6杂环烷基；其中所述Ci烷基，Ci烷基0Ci烷基，Ci^烷氧基和Ci^烷基磺酰基可以选择性地被一个或多个氟基取代；R4为Ci_4烷基，Ci_4烷基0Ci_4烷基，C5_6环烷基，或芳基；R5为Ci_4烷基，Ci_4氟烷基或Cs_6杂环烷基；Li为Ci_4烷基或键；L2为Ci_3烷基；除了化合物2-(环己基甲基)-3-氧代-N-[2-(三氟甲基)苄基]异吲哚啉-1-羧酰胺；以及其药学上可接受的盐，或其异构体的盐。本发明的化合物在治疗中如疼痛治疗中是有用的。

  公开号：

  WO2009145721A1

文献信息

• [EN] ISOINDOLINE DERIVATIVES COMPRISING PHENYL GROUPS AND THEIR USE IN THE TREATMENT OF PAIN DISORDERS<br/>[FR] DÉRIVÉS ISOINDOLINE COMPRENANT DES GROUPES PHÉNYLES ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES DE LA DOULEUR
  申请人：ASTRAZENECA AB

  公开号：WO2009145721A1

  公开（公告）日：2009-12-03

  Compounds of formula I are claimed, (I) wherein R1 is hydrogen, C1-3alkyl, Ci_3alkoxy, cyano, hydroxy or halo; and wherein said Ci^alkyl is optionally substituted by one or more substituents independently selected from hydroxy, Ci^alkoxy andfluoro; and said Ci^alkoxy is optionally substituted by one or morefluoro; m is 1 or 2; R2 and R3 is each and independently selected from hydrogen, Ci_4haloalkyl, Ci_4haloalkoxy, halo, Ci_4alkoxy, Ci_4alkyl and C3_7cycloalkyloxy; wherein said C3. γcycloalkyloxy is optionally substituted by one or morefluoro; and R2 and R3 may not both be hydrogen; D is C3_7cycloalkyl or C3_7heterocycloalkyl; and wherein said Cs-jcycloalkyl or Cs- γheterocycloalkyl may optionally be substituted by one or more X*; X4 is halo, Ci_3alkyl, Ci_3alkyl0Ci_3alkyl, Ci_3alkoxy, benzyl, Ci_4alkylsulfonyl, oxo, R4O(C=O), R5(C=O), or C5.6 heteroaryl; wherein said Cisalkyl, CisalkylOCisalkyl, Ci^alkoxy and C i^alkylsulfonyl is optionally substituted by one or more fluoro; R4 is Ci_4alkyl, Ci_4alkyl0Ci_4alkyl, C5_6cycloalkyl, or aryl; R5 is Ci_4alkyl, Ci_4fluoroalkyl or Cs_6 heteroaryl; Li is Ci_4alkylene or a bond; L2 is Ci_3alkylene; with the exception of the compound 2-(cyclohexylmethyl)-3-oxo-N-[2-(trifluoromethyl)benzyl]isoindoline-l-carboxamide; as well as a pharmaceutically acceptable salt, or isomer thereof, or a salt of said isomer. The compounds of the invention are useful in therapy such as pain therapy.

  公式I的化合物被要求，其中R1是氢，C1-3烷基，Ci_3烷氧基，氰基，羟基或卤素基；其中所述Ci^烷基可以选择性地被一个或多个取代基独立地选择自羟基，Ci^烷氧基和氟基；所述Ci^烷氧基可以选择性地被一个或多个氟基取代；m为1或2；R2和R3分别且独立地选择自氢，Ci_4卤代烷基，Ci_4卤代烷氧基，卤素，Ci_4烷氧基，Ci_4烷基和C3_7环烷氧基；其中所述C3. γ环烷氧基可以选择性地被一个或多个氟基取代；且R2和R3不能同时为氢；D为C3_7环烷基或C3_7杂环烷基；其中所述Cs-j环烷基或Cs-γ杂环烷基可以选择性地被一个或多个X*取代；X4为卤素，Ci_3烷基，Ci_3烷基0Ci_3烷基，Ci_3烷氧基，苄基，Ci_4烷基磺酰基，氧代，R4O(C=O)，R5(C=O)，或C5.6杂环烷基；其中所述Ci烷基，Ci烷基0Ci烷基，Ci^烷氧基和Ci^烷基磺酰基可以选择性地被一个或多个氟基取代；R4为Ci_4烷基，Ci_4烷基0Ci_4烷基，C5_6环烷基，或芳基；R5为Ci_4烷基，Ci_4氟烷基或Cs_6杂环烷基；Li为Ci_4烷基或键；L2为Ci_3烷基；除了化合物2-(环己基甲基)-3-氧代-N-[2-(三氟甲基)苄基]异吲哚啉-1-羧酰胺；以及其药学上可接受的盐，或其异构体的盐。本发明的化合物在治疗中如疼痛治疗中是有用的。
• [EN] SUBSTITUTED PYRROLOPYRIDINES AS ATR INHIBITORS<br/>[FR] PYRROLOPYRIDINES SUBSTITUÉES UTILISÉES EN TANT QU'INHIBITEURS D'ATR
  申请人：BLUEVALLEY PHARMACEUTICAL LLC

  公开号：WO2019050889A1

  公开（公告）日：2019-03-14

  The disclosure includes compounds of Formula (I) wherein A, W, m, R5, R6, R7, and R8, are defined herein. Also disclosed is a method for treating a neoplastic disease with these compounds.

  披露包括公式(I)中的化合物，其中A、W、m、R5、R6、R7和R8的定义如下。还披露了一种使用这些化合物治疗肿瘤性疾病的方法。
• [EN] PYRROLO CARBOXAMIDES AS MODULATORS OF ORPHAN NUCLEAR RECEPTOR RAR-RELATED ORPHAN RECEPTOR-GAMMA (RORϒ, NR1F3) ACTIVITY AND FOR THE TREATMENT OF CHRONIC INFLAMMATORY AND AUTOIMMUNE DISEASES<br/>[FR] PYRROLOCARBOXAMIDES EN TANT QUE MODULATEURS DE L'ACTIVITÉ D'UN RÉCEPTEUR ORPHELIN GAMMA (RORϒ, NR1F3) APPARENTÉ AU RÉCEPTEUR NUCLÉAIRE ORPHELIN RAR ET DESTINÉS AU TRAITEMENT DE MALADIES INFLAMMATOIRES CHRONIQUES ET AUTO-IMMUNES
  申请人：PHENEX PHARMACEUTICALS AG

  公开号：WO2013079223A1

  公开（公告）日：2013-06-06

  The invention provides modulators for the orphan nuclear receptor RORϒ and methods for treating RORϒ mediated diseases by administrating these novel RORϒ modulators to a human or a mammal in need thereof. Specifically, the present invention provides pyrrolo carboxamide compounds of Formula (1) and the enantiomers, diastereomers, N-oxides, tautomers, solvates and pharmaceutically acceptable salts thereof.

  本发明提供了针对孤儿核受体RORϒ的调节剂，以及通过向需要的人或哺乳动物施用这些新型RORϒ调节剂来治疗RORϒ介导的疾病的方法。具体而言，本发明提供了式(1)的吡咯甲酰胺化合物及其对映体、非对映体、N-氧化物、互变异构体、溶剂化物和药用可接受的盐。
• [EN] PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL, PYRROLO[2,3-B]PYRIDINYL ACRYLAMIDES AND EPOXIDES THEREOF<br/>[FR] PYRROLO [2,3-D] PYRIMIDINYL, PYRROLO[2,3-B] PYRAZINYL, PYRROLO [2,3-B] PYRIDINYL ACRYLAMIDES ET LEUR ÉPOXYDES
  申请人：PFIZER

  公开号：WO2016178110A1

  公开（公告）日：2016-11-10

  The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3- b]pyrazinyl,and pyrrolo[2,3-b]pyridinyl acrylamides, epoxides,and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

  本发明提供了具有药用活性的吡咯并[2,3-d]嘧啶基、吡咯并[2,3-b]吡嗪基和吡咯并[2,3-b]吡啶基的丙烯酰胺、环氧化物及其类似物。这些化合物对于抑制Janus激酶（JAK）具有用处。本发明还涉及包含制备这类化合物的方法的组合物，以及治疗和预防由JAK介导的疾病的方法。
• SUBSTITUTED PYRAZOLOPYRIMIDINES AND METHOD OF USE
  申请人：AbbVie Deutschland GmbH & Co. KG

  公开号：US20160304527A1

  公开（公告）日：2016-10-20

  Compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , L 1 and G 1 are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by positive allosteric modulation of the γ-aminobutyric acid B (GABA-B) receptor. Methods for making the compounds are described. Also described are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.

  具有化学式(I)及其药用可接受的盐的化合物，其中R1、R2、R3、R4、L1和G1如规范中定义的那样，对于治疗由γ-氨基丁酸B（GABA-B）受体的正向变构调节预防或改善的症状或疾病是有用的。描述了制备这些化合物的方法。还描述了具有化学式(I)的化合物的药物组合物，以及使用这些化合物和组合物的方法。