tert-butyl 3-amino-1-(4-chlorophenyl)propylcarbamate | 885595-59-5

• 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: tert-butyl 3-amino-1-(4-chlorophenyl)propylcarbamate
• 英文别名: [3-amino-1-(4-chloro-phenyl)-propyl]-carbamic acid tert-butyl ester；tert-butyl N-[3-amino-1-(4-chlorophenyl)propyl]carbamate
• CAS: 885595-59-5
• 化学式: C₁₄H₂₁ClN₂O₂
• 分子量: 284.786
• InChiKey: ASWDIABJPCJCQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-amino-1-(4-chlorophenyl)propylcarbamate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 4-amino-N-(1-(4-chlorophenyl)-3-(methylsulfonamido)propyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
  参考文献：
  名称：

  Discovery of 4-Amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases

  摘要：

  Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK. This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.

  DOI：

  10.1021/jm301762v
• 作为产物：
  描述：

  DL-对氯苯甘氨酸 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 碘 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 tert-butyl 3-amino-1-(4-chlorophenyl)propylcarbamate
  参考文献：
  名称：

  Discovery of 4-Amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases

  摘要：

  Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK. This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.

  DOI：

  10.1021/jm301762v

文献信息

• [EN] PYRROLO [2, 3 -D] PYRIMIDIN DERIVATIVES AS PROTEIN KINASE B INHIBITORS<br/>[FR] DÉRIVÉS PYRROLO[2,3-D]PYRIMIDINE COMME INHIBITEURS DE LA PROTÉINE KINASE B
  申请人：ASTRAZENECA AB

  公开号：WO2009047563A1

  公开（公告）日：2009-04-16

  The invention relates to a novel group of compounds of Formula (I) or salts thereof: wherein Y, Z1, Z2, R1, R4, R5 and n are as described in the specification, which may be useful in the treatment or prevention of a disease or medical condition mediated through protein kinase B (PKB) such as cancer. The invention also relates to pharmaceutical compositions comprising said compounds, methods of treatment of diseases mediated by PKB using said compounds and methods for preparing compounds of Formula (I).

  该发明涉及一类新型化合物，其化学式为（I）或其盐：其中Y、Z1、Z2、R1、R4、R5和n如规范中所述，这些化合物可能在通过蛋白激酶B（PKB）介导的疾病或医疗状况的治疗或预防中有用，例如癌症。该发明还涉及包含所述化合物的药物组合物，使用所述化合物治疗通过PKB介导的疾病的方法，以及制备化合物（I）的方法。
• Pharmaceutical Compounds
  申请人：Davies Thomas Glanmor

  公开号：US20090253718A1

  公开（公告）日：2009-10-08

  The invention provides a compound having the formula (I): or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR 5 ; J 1 -J 2 is N═C(R 6 ), (R 7 )C═N, (R 8 )N—C(O), (R 8 ) 2 C—C(O), N═N or (R 7 )C═C(R 6 ); A is an optionally substituted saturated C 1-7 hydrocarbon linker group having a maximum chain length of 5 atoms extending between R 1 and NR 2 R 3 and a maximum chain length of 4 atoms extending between E and NR 2 R 3 , one of the carbon atoms in the linker group being optionally replaced by oxygen or nitrogen; E is a monocyclic or bicyclic carbocyclic or heterocyclic group or an acyclic group X-G wherein X is CH 2 , O, S or NH and G is a C 1-4 alkylene chain wherein one of the carbon atoms is optionally replaced by O, S or NH; R 1 is hydrogen or an aryl or heteroaryl group; R 2 and R 3 are each hydrogen, optionally substituted C 1-4 hydrocarbyl or optionally substituted C 1-4 acyl; or NR 2 R 3 forms an imidazole group or a saturated monocyclic heterocyclic group having 4-7 ring members; or NR 2 R 3 and A together form a saturated monocyclic heterocyclic group having 4-7 ring members which is optionally substituted by C 1-4 alkyl; or NR 2 R 3 and the adjacent carbon atom of linker group A together form a cyano group; or R 1 , A and NR 2 R 3 together form a cyano group; and R 4 , R 5 , R 6 , R 7 and R 8 are each independently selected from hydrogen and various substituents as defined in the claims, wherein the compound is for use in: (a) the treatment or prophylaxis of a disease or condition in which the modulation (e.g. inhibition) of ROCK kinase or protein kinase p70S6K is indicated; and/or (b) the treatment of a subject or patient population in which the modulation (e.g. inhibition) of ROCK kinase or protein kinase p70S6K is indicated.

  本发明提供了具有以下式子（I）的化合物或其盐，溶剂化物，互变异构体或N-氧化物，其中T为N或CR5; J1-J2为N═C（R6），（R7）C═N，（R8）N—C（O），（R8）2C—C（O），N═N或（R7）C═C（R6）; A为最大链长为5个原子的选择性取代的饱和C1-7碳氢链连接基，在R1和NR2R3之间延伸，最大链长为4个原子，在E和NR2R3之间延伸，链连接基中的一个碳原子可以被氧或氮取代; E为单环或双环的碳环或杂环基团或一个无环的X-G基团，其中X为CH2，O，S或NH，G为一个C1-4烷基链，其中一个碳原子可以被O，S或NH取代; R1为氢或芳基或杂环基团; R2和R3分别为氢，选择性取代的C1-4烃基或选择性取代的C1-4酰基; 或NR2R3形成咪唑基团或具有4-7个环成员的饱和单环杂环基团; 或NR2R3和A一起形成一个被C1-4烷基取代的饱和单环杂环基团; 或NR2R3和链连接基A的相邻碳原子一起形成氰基团; 或R1，A和NR2R3一起形成氰基团; R4，R5，R6，R7和R8各自独立地选择氢和各种在权利要求中定义的取代基，其中该化合物用于：（a）治疗或预防调节ROCK激酶或蛋白激酶p70S6K所示的疾病或情况; 和/或（b）治疗调节ROCK激酶或蛋白激酶p70S6K所示的受试者或患者人群。
• Compounds for Treating Protein-Kinase Mediated Disorders
  申请人：Berdini Valerio

  公开号：US20080275029A1

  公开（公告）日：2008-11-06

  The invention provides a compound of the formula (I) or a salt, solvate, tautomer or N-oxide thereof for use in the treatment or prophylaxis of a disease state or condition mediated by protein kinase A and/or protein kinase B; wherein the ring Q is a benzene ring; J 2 -J 1 is N═CR 7 or R 1a N—CO; G is OH or NR 5 R 6 ; E is CONR 7 , NR 7 CO, C(R 8 )═C(R 8 ) or (X) m (CR 8 R 8a ) n where X is O, S or NR 7 ; provided that when J 2 -J 1 is R 1a N—CO, E is other than NR 7 CO; m and n are each 0 or 1, where m+n=1 or 2; A is a bond and R 4 and R 4a are absent or A is a saturated optionally substituted C 1-7 hydrocarbon linker group having a maximum chain length of 5 atoms extending between E and G, one carbon atom in the linker group A being optionally replaced by O or N; R 1 , R 1a , R 2 , and R 3 are each H; halogen; C 1-6 hydrocarbyl optionally substituted by halogen, OH or C 1-2 alkoxy; CN; CONHR 8 ; NH 2 ; NHCOR 10 or NHCONHR 10 ; R 4 is H or C 1-4 alkyl; R 4a is H, C 1-4 alkyl or a group R 9 ; R 5 and R 6 are each selected from H, R 9 and C 1-4 hydrocarbyl optionally substituted by halogen, C 1-2 alkoxy or R 9 ; or NR 5 R 6 forms a saturated 4-7 membered monocyclic heterocyclic group; R 7 is H or C 1-4 alkyl; R 8 and R 8a each H or saturated C 1-4 hydrocarbyl optionally substituted by fluorine; R 9 is a monocyclic or bicyclic carbocyclic or heterocyclic group containing up to 3 ring heteroatoms selected from N, O and S; or R 4 , R 4a and A together form a saturated monocyclic 4-7 membered heterocycle; or NR 5 R 6 , R 4 and A form a saturated 4-7 membered monocyclic heterocycle; or R 4 , together with R 7 or R 8 and A and E form a 4-7 membered saturated monocyclic heterocycle; or NR 5 R 6 and R 7 or R 8 together with A and E form a 4-7 membered saturated monocyclic heterocycle; and R 10 is optionally substituted phenyl or benzyl.

  该发明提供了一种式(I)的化合物或其盐、溶剂化物、互变异构体或N-氧化物，用于治疗或预防由蛋白激酶A和/或蛋白激酶B介导的疾病状态或病情；其中，环Q是苯环；J2-J1是N═CR7或R1aN—CO；G是OH或NR5R6；E是CONR7、NR7CO、C(R8)═C(R8)或(X)m(CR8R8a)n，其中X为O、S或NR7；但当J2-J1是R1aN—CO时，E为除NR7CO之外的其他化合物；m和n各为0或1，其中m+n=1或2；A是键，R4和R4a不存在或A是饱和的可选取代的C1-7烃链连接基，在E和G之间具有最大链长为5个原子，链连接基中的一个碳原子可被O或N取代；R1、R1a、R2和R3各为H、卤素、C1-6烃基，可选取代卤素、OH或C1-2烷氧基、CN、CONHR8、NH2、NHCOR10或NHCONHR10；R4为H或C1-4烷基；R4a为H、C1-4烷基或基团R9；R5和R6各为H、R9和C1-4烃基，可选取代卤素、C1-2烷氧基或R9；或NR5R6形成饱和的4-7成员的单环杂环基；R7为H或C1-4烷基；R8和R8a各为H或饱和的C1-4烃基，可选取代氟；R9为含有最多3个环杂原子（选自N、O和S）的单环或双环碳环或杂环基；或R4、R4a和A一起形成饱和的单环4-7成员杂环；或NR5R6、R4和A形成饱和的4-7成员单环杂环；或R4与R7或R8和A、E一起形成4-7成员饱和的单环杂环；或NR5R6与R7或R8一起与A和E形成4-7成员饱和的单环杂环；R10为可选取代苯基或苄基。
• Ortho-Condensed Pyridine and Pyrimidine Derivatives (e.g., Purines) as Protein Kinases Inhibitors
  申请人：Berdini Valerio

  公开号：US20090099213A1

  公开（公告）日：2009-04-16

  The invention provides a compound for use in the prophylaxis or treatment of a disease state or condition mediated by protein kinase B, the compound having the formula (I): or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR 5 ; J 1 -J 2 is N═C(R 6 ), (R 7 )C═N, (R 8 )N—C(O), (R 8 ) 2 C—C(O), N═N or (R 7 )C═C(R 6 ); A is an optionally substituted saturated C 1-7 hydrocarbon linker group having a maximum chain length of 5 atoms extending between R 1 and NR 2 R 3 and a maximum chain length of 4 atoms extending between E and NR 2 R 3 , one of the carbon atoms in the linker group being optionally replaced by oxygen or nitrogen; E is a monocyclic or bicyclic carbocyclic or heterocyclic group or an acyclic group X-G wherein X is CH 2 , O, S or NH and G is a C 1-4 alkylene chain wherein one of the carbon atoms is optionally replaced by O, S or NH; R 1 is hydrogen or an aryl or heteroaryl group; R 2 and R 3 are each hydrogen, optionally substituted C 1-4 hydrocarbyl or optionally substituted C 1-4 acyl; or NR 2 R 3 forms an imidazole group or a saturated monocyclic heterocyclic group having 4-7 ring members; or NR 2 R 3 and A together form a saturated monocyclic heterocyclic group having 4-7 ring members which is optionally substituted by C 1-4 alkyl; or NR 2 R 3 and the adjacent carbon atom of linker group A together form a cyano group; or R 1 , A and NR 2 R 3 together form a cyano group; and R 4 , R 5 , R 6 , R 7 and R 8 are each independently selected from hydrogen and various substituents as defined in the claims.

  本发明提供了一种化合物，可用于预防或治疗由蛋白激酶B介导的疾病状态或病况，该化合物具有以下式（I）或其盐，溶剂化合物，互变异构体或N-氧化物，其中T为N或CR5；J1-J2为N═C（R6），（R7）C═N，（R8）N—C（O），（R8）2C—C（O），N═N或（R7）C═C（R6）；A为一个可选取代的饱和C1-7碳链连接基团，其最大链长为5个原子，延伸在R1和NR2R3之间，并且最大链长为4个原子，延伸在E和NR2R3之间，连接基团中的一个碳原子可被氧或氮取代；E为单环或双环碳环或杂环基团或一个无环基团X-G，其中X为CH2，O，S或NH，G为C1-4烷基链，其中一个碳原子可被O，S或NH取代；R1为氢或芳基或杂芳基团；R2和R3分别为氢，可选取代的C1-4烃基或可选取代的C1-4酰基；或NR2R3形成咪唑基团或具有4-7个环成员的饱和单环杂环基团；或NR2R3和A一起形成具有4-7个环成员的饱和单环杂环基团，该基团可选取代为C1-4烷基；或NR2R3和连接基团A的相邻碳原子一起形成氰基团；或R1，A和NR2R3一起形成氰基团；R4，R5，R6，R7和R8各自独立地选择氢和各种定义中定义的取代基。
• Substituted pyrrolo[2,3-d]pyrimidine as a protein kinase B inhibitor
  申请人：AstraZeneca AB

  公开号：US08101623B2

  公开（公告）日：2012-01-24

  The invention relates to a novel group of compounds of Formula (I) or salts thereof: wherein Y, Z1, Z2, R1, R4, R5 and n are as described in the specification, which may be useful in the treatment or prevention of a disease or medical condition mediated through protein kinase B (PKB) such as cancer. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I), methods of treatment of diseases mediated by PKB using said compounds and methods for preparing compounds of Formula (I).

  本发明涉及一类新的化合物组合式（I）或其盐：其中Y、Z1、Z2、R1、R4、R5和n的描述如规范中所述，这些化合物可以用于治疗或预防通过蛋白激酶B（PKB）介导的疾病或医疗情况，如癌症。本发明还涉及包含化合物组合式（I）的制药组合物、使用该化合物治疗PKB介导的疾病的方法以及制备化合物组合式（I）的方法。