4-benzyl-4,7-diazaspiro[2.5]octane | 611235-29-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-benzyl-4,7-diazaspiro[2.5]octane
• CAS: 611235-29-1
• 化学式: C₁₃H₁₈N₂
• 分子量: 202.299
• InChiKey: CSELKLIMQOUJMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-benzyl-4,7-diazaspiro[2.5]octane 、 2,3-二甲基溴苯 在 chloro(2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1’-biphenyl)[2-(2’-amino-1,1‘-biphenyl)]palladium(II) 2nd generation 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 4-benzyl-7-(2,3-dimethylphenyl)-4,7-diazaspiro[2.5]octane
  参考文献：
  名称：

  [EN] NOVEL SUBSTITUTED PIPERAZINE AMIDE COMPOUNDS AS INDOLEAMINE 2, 3-DIOXYGENASE (IDO) INHIBITORS
  [FR] NOUVEAUX COMPOSÉS DE PIPERAZINE AMIDE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE (IDO)

  摘要：

  本文披露了一种化合物，其化学式为（I），可以作为IDO酶的抑制剂：（I）。本文还披露了这些化合物在潜在的治疗或预防IDO相关疾病或紊乱中的用途。本文还披露了包含这些化合物的组合物。此外，本文还披露了这些组合物在潜在的治疗或预防IDO相关疾病或紊乱中的用途。

  公开号：

  WO2020112581A1
• 作为产物：
  描述：

  tert-butyl 4-benzyl-4,7-diazaspiro[2.5]octane-7-carboxylate 在 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 16.0h， 以100%的产率得到4-benzyl-4,7-diazaspiro[2.5]octane
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS AS JAK RECEPTOR AND PROTEIN TYROSINE KINASE INHIBITORS
  [FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU’INHIBITEURS DU RÉCEPTEUR JAK ET DE LA PROTÉINE TYROSINE KINASE

  摘要：

  该发明涉及通用式（I）的化合物，其中A，R1，R2，R3，R4，R5，R9，m和n如本文所定义，以及其在治疗中的药用盐、水合物或溶剂合物，可单独使用或与一个或多个其他药用活性化合物结合使用，作为JAK激酶和蛋白酪氨酸激酶抑制剂，用于预防、治疗或改善疾病及其并发症，包括例如牛皮癣、特应性皮炎、酒渣鼻、红斑狼疮、多发性硬化、类风湿关节炎、I型糖尿病、哮喘、癌症、自身免疫性甲状腺疾病、溃疡性结肠炎、克罗恩病、阿尔茨海默病、白血病、眼疾如糖尿病视网膜病变和黄斑变性，以及其他自身免疫疾病和需要免疫抑制的适应症，例如器官移植中。

  公开号：

  WO2011003418A1

文献信息

• [EN] NOVEL SULFAMIDE PIPERAZINE DERIVATIVES AS PROTEIN TYROSINE KINASE INHIBITORS AND PHARMACEUTICAL USE THEREOF<br/>[FR] NOUVEAUX DÉRIVÉS DE SULFAMIDE PIPÉRAZINE À TITRE D'INHIBITEURS DE PROTÉINES TYROSINE KINASES ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：LEO PHARMA AS

  公开号：WO2012093169A1

  公开（公告）日：2012-07-12

  The invention relates to compounds of general Formula (I), Wherein R1, R2, R3, R4, R5, m, n are defined herein, and pharmaceutically acceptable salts, prodrugs, hydrates, or solvates thereof, for use - alone or in combination with one or more other pharmaceutically active compounds- in therapy, as JAK kinase and protein tyrosine kinase inhibitors for preventing, treating or ameliorating diseases and complications thereof, including, for example, psoriasis, atopic dermatitis, rosacea, lupus, multiple sclerosis, rheumatoid arthritis, Type I diabetes, asthma, cancer, autoimmune thyroid disorders, ulcerative colitis, Crohn's disesase, Alzheimer's disease, leukaemia, eye diseases such as diabetic retinopathy and macular degeneration as well as other autoimmune diseases and indications where immunosuppression would be desirable for example in organ transplantation.

  该发明涉及一般式(I)的化合物，其中R1、R2、R3、R4、R5、m、n在此处定义，并且其药用可接受的盐、前药、水合物或溶剂化合物，用于单独或与一个或多个其他药用活性化合物结合在一起，在治疗中使用，作为JAK激酶和蛋白酪氨酸激酶抑制剂，用于预防、治疗或改善疾病及其并发症，包括例如牛皮癣、特应性皮炎、酒渣鼻、狼疮、多发性硬化症、类风湿关节炎、I型糖尿病、哮喘、癌症、自身免疫性甲状腺疾病、溃疡性结肠炎、克罗恩病、阿尔茨海默病、白血病、眼部疾病如糖尿病视网膜病变和黄斑变性以及其他自身免疫性疾病和免疫抑制希望的适应症，例如在器官移植中。
• [EN] 5- (4- (HALOALKOXY) PHENYL) PYRIMIDINE-2-AMINE COMPOUNDS AND COMPOSITIONS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS ET COMPOSITIONS DE 5- (4- (HALOALKOXY) PHÉNYL) PYRIMIDINE-2-AMINE UTILISÉS COMME INHIBITEURS DE KINASES
  申请人：IRM LLC

  公开号：WO2009026276A1

  公开（公告）日：2009-02-26

  The invention provides compounds of formula (1) and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit, PDGFRα, PDGFRβ, CSF1R, AbI, BCR-AbI, CSK, JNK1, JNK2, p38, p70S6K, TGFβ, SRC, EGFR, trkB, FGFR3. Fes, Lck, Syk, RAF, MKK4, MKK6, SAPK2β, BRK, Fms, KDR, c-rapor b-raf kinases.

  该发明提供了式（1）的化合物及其制药组合物，可用作蛋白激酶抑制剂，以及使用这些化合物治疗、改善或预防与异常或调节的激酶活性相关的疾病的方法。在某些实施方式中，该发明提供了使用这些化合物来治疗、改善或预防涉及c-kit、PDGFRα、PDGFRβ、CSF1R、AbI、BCR-AbI、CSK、JNK1、JNK2、p38、p70S6K、TGFβ、SRC、EGFR、trkB、FGFR3、Fes、Lck、Syk、RAF、MKK4、MKK6、SAPK2β、BRK、Fms、KDR、c-rapor、b-raf激酶的疾病或紊乱的方法。
• [EN] HETEROCYCLIC COMPOUNDS AS JAK RECEPTOR AND PROTEIN TYROSINE KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU’INHIBITEURS DU RÉCEPTEUR JAK ET DE LA PROTÉINE TYROSINE KINASE
  申请人：LEO PHARMA AS

  公开号：WO2011003418A1

  公开（公告）日：2011-01-13

  The invention relates to compounds of general formula (I) wherein A, R1, R2, R3, R4, R5, R9, m and n are defined as defined herein, and pharmaceutically acceptable salts, hydrates, or solvates thereof, for use -alone or in combination with one or more other pharmaceutically active compounds- in therapy, as JAK kinase and protein tyrosine kinase inhibitors for preventing, treating or ameliorating diseases and complications thereof, including, for example, psoriasis, atopic dermatitis, rosacea, lupus, multiple sclerosis, rheumatoid arthritis, Type I diabetes, asthma, cancer, autoimmune thyroid disorders, ulcerative colitis, Crohn's disesase, Alzheimer's disease, leukaemia, eye diseases such as diabetic retinopathy and macular degeneration as well as other autoimmune diseases and indications where immunosuppression would be desirable for example in organ transplantation.

  该发明涉及通用式（I）的化合物，其中A，R1，R2，R3，R4，R5，R9，m和n如本文所定义，以及其在治疗中的药用盐、水合物或溶剂合物，可单独使用或与一个或多个其他药用活性化合物结合使用，作为JAK激酶和蛋白酪氨酸激酶抑制剂，用于预防、治疗或改善疾病及其并发症，包括例如牛皮癣、特应性皮炎、酒渣鼻、红斑狼疮、多发性硬化、类风湿关节炎、I型糖尿病、哮喘、癌症、自身免疫性甲状腺疾病、溃疡性结肠炎、克罗恩病、阿尔茨海默病、白血病、眼疾如糖尿病视网膜病变和黄斑变性，以及其他自身免疫疾病和需要免疫抑制的适应症，例如器官移植中。
• [EN] INDOLYLMALEIMIDE DERIVATIVES<br/>[FR] DÉRIVÉS D'INDOLYLMALÉIMIDE
  申请人：NOVARTIS AG

  公开号：WO2003082859A1

  公开（公告）日：2003-10-09

  Provided are compounds of Formula (I), which are useful in the treatment and/or prevention of diseases or disorders mediated by T lymphocytes and/or PKC, e.g. acute or chronic rejection of organ or tissue allo- or xenografts, graft versus host diseases, atherosclerosis, vascular occlusion due to vascular injury such as angioplasty, restenosis, obesity, syndrome X, impaired glucose tolerance, polycystic ovary syndrome, hypertension, heart failure, chronic obstructive pulmonary disease, CNS diseases such as Alzheimer disease or amyotrophic lateral sclerosis, cancer, infectious diseases such as AIDS, septic shock or adult respiratory distress syndrome, ischemia/reperfusion injury e.g. myocardial infraction, stroke, gut ischemia, renal failure or hemorrhage shock, or traumatic shock, e.g. traumatic brain injury. The compounds of (I) are also useful in the treatment and/or prevention of T-cell mediated acute or chronic inflammatory diseases or disorders or autoimmune diseases e.g. rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Hashimoto’s thyroidis, multiple sclerosis, myasthenia gravis, diabetes type I or II and the disorders associated therewith, e.g. angiopathy, diabetic proliferative retinopathy, diabetic macular edema, nephropathy, neuropathy and dawn phenomenon, respiratory diseases such as asthma or inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury, cutaneous manifestations of immunologically-mediated disorders or illnesses, inflammatory and hyperproliferative skin diseases (such as psoriasis, atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis and further eczematous dermatitises, seborrhoeic dermatitis), inflammatory eye diseases, e.g. Sjoegren’s syndrome, keratoconjunctivitis or uveitis, inflammatory bowel disease, Crohn’s disease or ulcerative colitis.

  提供的是化合物的化学式（I），可用于治疗和/或预防由T淋巴细胞和/或PKC介导的疾病或紊乱，例如器官或组织同种异体或异种移植的急性或慢性排斥、移植物抗宿主病、动脉粥样硬化、由血管损伤引起的血管闭塞，如血管成形术后的再狭窄、肥胖、X综合征、糖耐量受损、多囊卵巢综合征、高血压、心力衰竭、慢性阻塞性肺疾病、中枢神经系统疾病，如阿尔茨海默病或肌萎缩侧索硬化、癌症、感染性疾病，如艾滋病、脓毒性休克或成人呼吸窘迫综合征、缺血/再灌注损伤，例如心肌梗死、中风、肠道缺血、肾功能衰竭或出血性休克，或创伤性休克，例如创伤性脑损伤。化合物（I）也可用于治疗和/或预防T细胞介导的急性或慢性炎症性疾病或紊乱或自身免疫性疾病，例如类风湿性关节炎、骨关节炎、系统性红斑狼疮、Hashimoto甲状腺炎、多发性硬化症、重症肌无力、糖尿病I型或II型及相关疾病，例如血管病、糖尿病性增生性视网膜病变、糖尿病性黄斑水肿、肾病、神经病和晨间现象、呼吸系统疾病，如哮喘或炎症性肺损伤、炎症性肝损伤、炎症性肾小球损伤、免疫介导疾病或疾病的皮肤表现、炎症性和过度增生性皮肤疾病（如银屑病、特应性皮炎、过敏性接触性皮炎、刺激性接触性皮炎和其他湿疹性皮炎、脂溢性皮炎）、炎症性眼部疾病，如干燥综合征、角膜结膜炎或葡萄膜炎、炎症性肠疾病、克罗恩病或溃疡性结肠炎。
• Indolylmaleimide derivatives
  申请人：Evenou Jean-Pierre

  公开号：US20050119274A1

  公开（公告）日：2005-06-02

  Provided are compounds of formula (I) which are useful in the treatment and/or prevention of diseases or disorders mediated by T lymphocytes and/or PKC, e.g. acute or chronic rejection of organ or tissue allo- or xenografts, graft versus host diseases, atherosclerosis, vascular occlusion due to vascular injury such as angioplasty, restenosis, obesity, syndrome X, impaired glucose tolerance, polycystic ovary syndrome, hypertension, heart failure, chronic obstructive pulmonary disease, CNS diseases such as Alzheimer disease or amyotrophic lateral sclerosis, cancer, infectious diseases such as AIDS, septic shock or adult respiratory distress syndrome, ischemia/reperfusion injury e.g. myocardial infarction, stroke, gut ischemia, renal failure or hemorrhage shock, or traumatic shock, e.g. traumatic brain injury. The compounds of formula I are also useful in the treatment and/or prevention of T-cell mediated acute or chronic inflammatory disease or disorders or autoimmune diseases e.g. rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Hashimoto's thyroidis, multiple sclerosis, myasthenia gravis, diabetes type I or II and the disorders associated therewith, e.g. angiopathy, diabetic proliferative retinopathy, diabetic macular edema, nephropathy, neuropathy and dawn phenomenon, respiratory diseases such as asthma or inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury, cutaneous manifestations of immunologically-mediated disorders or illnesses, inflammatory and hyperproliferative skin diseases (such as psoriasis, atopic dermatitis, allergic contract dermatitis, irritant contact dermatitis and further eczematous dermatitises, seborrhoeic dermatitis), inflammatory eye diseases, e.g. Sjoegren's syndrome, keratoconjunctivitis or uveitis, inflammatory bowel disease, Crohn's disease or ulcerative colitis.

  提供的化合物式(I)可用于治疗和/或预防由T淋巴细胞和/或PKC介导的疾病或疾病，例如器官或组织同种或异种移植的急性或慢性排斥反应，移植物抗宿主病，动脉粥样硬化，由于血管损伤如血管成形术而导致的血管闭塞，再狭窄，肥胖，综合征X，糖耐量受损，多囊卵巢综合症，高血压，心力衰竭，慢性阻塞性肺疾病，中枢神经系统疾病，例如阿尔茨海默病或肌萎缩侧索硬化，癌症，传染病，例如艾滋病，脓毒症或成人呼吸窘迫综合征，缺血/再灌注损伤，例如心肌梗塞，中风，肠道缺血，肾衰竭或出血性休克，或创伤性休克，例如创伤性脑损伤。公式I的化合物也可用于治疗和/或预防T细胞介导的急性或慢性炎症性疾病或疾病或自身免疫性疾病，例如类风湿性关节炎，骨关节炎，系统性红斑狼疮，桥本甲状腺炎，多发性硬化症，重症肌无力，糖尿病I型或II型及其相关疾病，例如血管病，糖尿病增生性视网膜病变，糖尿病黄斑水肿，肾病，神经病和黎明现象，呼吸道疾病，例如哮喘或炎性肺损伤，炎性肝损伤，炎性肾小球损伤，免疫介导疾病或疾病的皮肤表现，炎症和过度增生性皮肤疾病（例如银屑病，特应性皮炎，过敏性接触性皮炎，刺激性接触性皮炎和进一步的湿疹性皮炎，脂溢性皮炎），炎症性眼疾，例如干燥综合征，角膜结膜炎或葡萄膜炎，炎症性肠病，克隆氏病或溃疡性结肠炎。