(4S)-4-(2-甲基丙基)-2-(三氟甲基)-1,3-恶唑烷 | 671818-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: (4S)-4-(2-甲基丙基)-2-(三氟甲基)-1,3-恶唑烷
• 英文名称: (4S)-4-isobutyl-2-trifluoromethyl-oxazolidine
• 英文别名: (S)-4-isobutyl-2-trifluoromethyl-oxazolidine；Oxazolidine, 4-(2-methylpropyl)-2-(trifluoromethyl)-, (4S)-；(4S)-4-(2-methylpropyl)-2-(trifluoromethyl)-1,3-oxazolidine
• CAS: 671818-85-2
• 化学式: C₈H₁₄F₃NO
• 分子量: 197.2
• InChiKey: IYTIXZWGGKYGOR-PKPIPKONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4S)-4-(2-甲基丙基)-2-(三氟甲基)-1,3-恶唑烷 在 chromium(VI) oxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 高碘酸 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 17.0h， 生成 N²-[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N¹-(cyanomethyl)-L-leucinamide
  参考文献：
  名称：

  三氟乙胺作为组织蛋白酶K抑制剂中的酰胺等排物。

  摘要：

  二肽组织蛋白酶K抑制剂的P2-P3酰胺可以被代谢稳定的三氟乙胺基取代。氮的非碱性性质允许与Gly66形成重要的氢键。所得化合物的效力比相应的酰胺衍生物高10至20倍。化合物8是人组织蛋白酶K的5 pM抑制剂，其选择性是其他组织蛋白酶的10,000倍以上。

  DOI：

  10.1016/j.bmcl.2005.07.071
• 作为产物：
  描述：

  L-亮氨醇 、 三氟乙醛缩甲基半醇 在 4-甲基苯磺酸吡啶 作用下， 以 甲苯 为溶剂， 生成 (4S)-4-(2-甲基丙基)-2-(三氟甲基)-1,3-恶唑烷
  参考文献：
  名称：

  Diastereoselective Arylithium Addition to an α-Trifluoromethyl Imine. Practical Synthesis of a Potent Cathepsin K Inhibitor

  摘要：

  A practical, chromatography-free synthesis of potent cathepsin K inhibitor 1 is described. The addition of 4-bromophenyllithium to an alpha-trifluoromethylimine derived from commercially available (S)-leucinol was accomplished in a highly diastereoselective manner (97.6% de, 91% yield). Subsequent Suzuki cross-coupling afforded biaryl 7. Oxidation of the alcohol and sulfide functionalities led to the formation of carboxylic acid 8. Crystallization of 7 and acid 8 as its dicyclohexylamine salt gave excellent impurity rejection. The final amide coupling with commercially available aminoacetonitrile hydrochloride afforded 1 in excellent purity (99.6A% by HPLC, 100% de, < 3 ppm Pd, W, Cr).

  DOI：

  10.1021/jo052430j

文献信息

• Cysteine Protease Inhibitors
  申请人：Tickle David

  公开号：US20090023747A1

  公开（公告）日：2009-01-22

  A compound of the formula (II) wherein one of R 1 and R 2 is halo and the other is H or halo; R 3 is —C 1 -C 5 straight or branched chain, optionally fluorinated, alkyl or —CH 2 CR 5 C 3 -C 4 -Cycloalkyl; R 4 is H; R 5 is H, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, hydroxyl, OC 1 -C 2 alkyl, fluoro; R 6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or heterocycle wherein the or each ring has 4, 5 or 6 ring atoms and 0 to 3 hetero atoms selected from S, O and N; Rb is haloalkyl; Rc is H or C 1 -C 4 alkyl; and pharmaceutically acceptable salts, hydrates or N-oxides thereof have utility in the treatment of disorders characterised by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

  化合物的公式（II），其中R1和R2中的一个是卤素，另一个是氢或卤素; R3是直链或支链，可选择氟化的C1-C5烷基或-CH2CR5C3-C4环烷基; R4是氢; R5是氢，C1-C2烷基，C1-C2卤代烷基，羟基，OC1-C2烷基，氟; R6是稳定的，可选地取代的单环或双环，碳环或杂环，其中每个环具有4、5或6个环原子和0到3个从S、O和N中选择的杂原子; Rb是卤代烷基; Rc是氢或C1-C4烷基;以及其药学上可接受的盐，水合物或N-氧化物在治疗由于cathepsin K不适当的表达或激活而表现出来的疾病中具有用途，如骨质疏松症、骨关节炎、类风湿性关节炎或骨转移。
• Oxazolidine Ring Opening and Isomerization to (<i>E</i>)-Imines. Asymmetric Synthesis of Aryl-α-fluoroalkyl Amino Alcohols
  作者：Francis Gosselin、Amélie Roy、Paul D. O'Shea、Cheng-yi Chen、Ralph P. Volante

  DOI：10.1021/ol036486g

  日期：2004.2.1

  A base-induced ring opening/imine isomerization/diastereoselective organometallic addition sequence on 4-substituted 2-perfluoroalkyl-1,3-oxazolidines has been developed for the asymmetric synthesis of aryl alpha-perfluoroalkylamine derivatives. This practical method provides chiral amino alcohols in 60-95% yield with uniformely high diastereoselectivities ranging from 35:1 to >100:1.
• WO2007/6716
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] CYSTEINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE CYSTEINE PROTEASE
  申请人：MEDIVIR AB

  公开号：WO2007006716A1

  公开（公告）日：2007-01-18

  [EN] A compound of the formula (II) wherein one of R¹ and R² is halo and the other is H or halo; R³ is -C₁-C₅ straight or branched chain, optionally fluorinated, alkyl or -CH₂CR⁵C₃-C₄-Cycloalkyl; R⁴ is H; R⁵ is H, C₁-C₂ alkyl, C₁-C₂ haloalkyl, hydroxyl, OC₁-C₂alkyl, fluoro; R⁶ is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or hetorocycle wherein the or each ring has 4, 5 or 6 ring atoms and 0 to 3 hetero atoms selected from S, O and N; Rb is haloalkyl; Rc is H or C₁-C₄ alkyl; and pharmaceutically acceptable salts, hydrates or N-oxides thereof have utility in the treatment of disorders characterised by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
  [FR] Composé de formule (II) sachant que R¹ et R² est halo et que l'autre est H ou halo ; R³ est une chaîne -C₁-C₅ droite ou ramifiée, éventuellement fluorée, alkyle -CH₂CR⁵C₃-C₄-cycloalkyle; R⁴ est H; R⁵ est H, C₁-C₂ alkyle, C₁-C₂ haloalkyle, hydroxyle, OC₁-C₂alkyle, fluoro; R⁶ est un carbocycle ou hétérocycle monocyclique ou bicyclique stable, éventuellement substitué, et le cycle ou chaque cycle comporte 4, 5 ou 6 atomes de cycle et entre 0 et 3 hétéroatomes pouvant être S, O et N; est haloalkyle; Rc est H ou C₁-C₄ alkyle; y compris les sels, hydrates ou N-oxydes pharmaceutiquement acceptables d'un tel composé. Ce type de composé est utile pour le traitement de troubles dont la médiation est assurée par une expression ou activation inadéquate de la cathepsine K, du type ostéoporose, arthrose, polyarthrite rhumatoïde ou métastase osseuse.
• Trifluoroethylamines as amide isosteres in inhibitors of cathepsin K
  作者：W. Cameron Black、Christopher I. Bayly、Dana E. Davis、Sylvie Desmarais、Jean-Pierre Falgueyret、Serge Léger、Chun Sing Li、Frédéric Massé、Daniel J. McKay、James T. Palmer、M. David Percival、Joël Robichaud、Nancy Tsou、Robert Zamboni

  DOI：10.1016/j.bmcl.2005.07.071

  日期：2005.11

  P2-P3 amide of dipeptide cathepsin K inhibitors can be replaced by the metabolically stable trifluoroethylamine group. The non-basic nature of the nitrogen allows the important hydrogen bond to Gly66 to be made. The resulting compounds are 10- to 20-fold more potent than the corresponding amide derivatives. Compound 8 is a 5 pM inhibitor of human cathepsin K with >10,000-fold selectivity over other cathepsins

  二肽组织蛋白酶K抑制剂的P2-P3酰胺可以被代谢稳定的三氟乙胺基取代。氮的非碱性性质允许与Gly66形成重要的氢键。所得化合物的效力比相应的酰胺衍生物高10至20倍。化合物8是人组织蛋白酶K的5 pM抑制剂，其选择性是其他组织蛋白酶的10,000倍以上。