tert-butyl methyl(trans-4-(2-oxoethyl)cyclohexyl)carbamate | 400899-28-7

• 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
• 英文名称: tert-butyl methyl(trans-4-(2-oxoethyl)cyclohexyl)carbamate
• 英文别名: trans-[Methyl-[4-(2-oxo-ethyl)-cyclohexyl]-carbamic acid tert-butyl ester]
• CAS: 400899-28-7
• 化学式: C₁₄H₂₅NO₃
• 分子量: 255.357
• InChiKey: NOWOVFGBWCTGCW-HAQNSBGRSA-N

物化性质

• 沸点：
  344.5±11.0 °C(predicted)
• 密度：
  1.02±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.0
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl methyl(trans-4-(2-oxoethyl)cyclohexyl)carbamate 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 三乙酰氧基硼氢化钠 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 N-(trans-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)-ethyl)cyclohexyl)-N-methyl-1H-indole-2-carboxamide
  参考文献：
  名称：

  Structure–Activity Study of N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D₂ Receptor

  摘要：

  We recently demonstrated that 5B269652 (1) engages one protomer of a dopamine D-2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural determinants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric "head" groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R "privileged structures" generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharmacology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R.

  DOI：

  10.1021/acs.jmedchem.5b00581
• 作为产物：
  描述：

  对硝基苯乙酸 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， -78.0~20.0 ℃ 、413.7 kPa 条件下， 反应 157.0h， 生成 tert-butyl methyl(trans-4-(2-oxoethyl)cyclohexyl)carbamate
  参考文献：
  名称：

  Structure–Activity Study of N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D₂ Receptor

  摘要：

  We recently demonstrated that 5B269652 (1) engages one protomer of a dopamine D-2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural determinants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric "head" groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R "privileged structures" generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharmacology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R.

  DOI：

  10.1021/acs.jmedchem.5b00581

文献信息

• Chromene compounds, a process for their preparationand pharmaceutical compositions containing them
  申请人：De Nanteuil Guillaume

  公开号：US20110021490A1

  公开（公告）日：2011-01-27

  The invention relates to compounds of formula (I): wherein R 1 and R 2 together form the following carbon-containing chain: wherein: R 3 represents a hydrogen atom or an alkyl group, R 4 represents a hydrogen atom or an alkyl, aryl, heteroaryl, 3,4-dioxocyclobutenyl, alkylcarbonyl, cycloalkylcarbonyl, heterocycloalkylcarbonyl, benzoyl, arylsulphonyl or heteroarylsulphonyl group, each of those groups optionally being substituted, or R 3 and R 4 together with the nitrogen atom carrying them form a 5- to 8-membered ring, the ring thereby formed optionally being substituted. Medicinal products containing the same which are useful in treating conditions requiring a D3 receptor antagonist.

  该发明涉及以下式（I）的化合物： 其中R1和R2共同形成以下含碳链： 其中： R3代表氢原子或烷基基团， R4代表氢原子或烷基、芳基、杂芳基、3,4-二氧代环丁烯基、烷基羰基、环烷基羰基、杂环烷基羰基、苯甲酰基、芳基磺酰基或杂芳基磺酰基基团，其中每个基团可选择地被取代， 或者R3和R4与携带它们的氮原子共同形成一个5-至8-成员环，因此形成的环可选择地被取代。 含有这些化合物的药物制剂在治疗需要D3受体拮抗剂的病症中很有用。
• 2,3-oxidosqualene-lanosterol cyclase inhibitors
  申请人：——

  公开号：US20020045777A1

  公开（公告）日：2002-04-18

  The present invention relates to aminocyclohexanol derivatives useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes.

  本发明涉及氨基环己醇衍生物，用于治疗和/或预防与2,3-氧化甾二烯-鲨烯合酶相关的疾病，如高胆固醇血症、高脂血症、动脉硬化、血管疾病、真菌病、胆结石、肿瘤和/或增生性疾病，以及治疗和/或预防糖耐量受损和糖尿病。
• Substituted cyclohexane derivatives
  申请人：——

  公开号：US20030186984A1

  公开（公告）日：2003-10-02

  The present invention relates to compounds of formula (I) 1 wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , U, V, m, n and o are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the 2,3-oxidosqualene-lanosterol cyclase biosynthetic pathway such as hypercholesterolemia and hyperlipemia.

  本发明涉及式(I)的化合物，其中A1、A2、A3、A4、A5、A6、U、V、m、n和o如规范中定义的那样，以及其药学上可接受的盐。这些化合物对于治疗和/或预防与2,3-氧化甾二烯-鲨烯合成途径相关的疾病，如高胆固醇血症和高脂血症，是有用的。
• 2,3-Oxidosqualene-lanosterol cyclase inhibitors
  申请人：Ackermann Jean

  公开号：US20050176766A1

  公开（公告）日：2005-08-11

  The present invention relates to aminocyclohexanol derivatives useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes.

  本发明涉及氨基环己醇衍生物，用于治疗和/或预防与2,3-氧化角鲨烯-鲨烯环化酶相关的疾病，如高胆固醇血症、高脂血症、动脉硬化、血管疾病、真菌感染、胆结石、肿瘤和/或过度增殖性疾病，以及治疗和/或预防糖耐量受损和糖尿病。
• NOVEL AMINOCYCLOHEXANE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1311475A1

  公开（公告）日：2003-05-21