[(1R,2S)-1-benzyl-3-benzylamino-2-hydroxy-propyl]-carbamic acid tert-butyl ester | 853904-62-8

• 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: [(1R,2S)-1-benzyl-3-benzylamino-2-hydroxy-propyl]-carbamic acid tert-butyl ester
• 英文别名: [(1R,2S)-1-Benzyl-3-benzylamino-2-hydroxy-propyl]-carbamic acid tert-butyl ester；tert-butyl N-[(2R,3S)-4-(benzylamino)-3-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 853904-62-8
• 化学式: C₂₂H₃₀N₂O₃
• 分子量: 370.492
• InChiKey: HPKGQAMBRUMGSX-UXHICEINSA-N

物化性质

• 沸点：
  545.1±50.0 °C(Predicted)
• 密度：
  1.107±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(1R,2S)-1-benzyl-3-benzylamino-2-hydroxy-propyl]-carbamic acid tert-butyl ester 在 lithium hydroxide 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 methyl (2R)-2-[[(2R)-2-[[benzyl-[(2S,3R)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutyl]carbamoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoate
  参考文献：
  名称：

  Stereochemical Analysis of (Hydroxyethyl)urea Peptidomimetic Inhibitors of γ-Secretase

  摘要：

  (Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3' with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked gamma-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts. selected all D-amino acid containing analogues were equipotent. to their counterparts in a cell-based assay when incubated for extended times.

  DOI：

  10.1021/jm049566e
• 作为产物：
  描述：

  (R)-tert-butyl (4-bromo-3-oxo-1-phenylbutan-2-yl)carbamate 在 dimethyl sulfide borane 、 sodium methylate 、 (S)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 甲醇 、 异丙醇 、 甲苯 为溶剂， 反应 14.5h， 生成 [(1R,2S)-1-benzyl-3-benzylamino-2-hydroxy-propyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Stereochemical Analysis of (Hydroxyethyl)urea Peptidomimetic Inhibitors of γ-Secretase

  摘要：

  (Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3' with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked gamma-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts. selected all D-amino acid containing analogues were equipotent. to their counterparts in a cell-based assay when incubated for extended times.

  DOI：

  10.1021/jm049566e

文献信息

• 1-Amino Linked Compounds
  申请人：Blaszczak Larry Chris

  公开号：US20080207735A1

  公开（公告）日：2008-08-28

  The present invention is directed to compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein A is (II); X is selected from CH, CF and N, R8 is selected from H, C 1 -C 6 alkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, C 1 -C 6 alkylheteroaryl, C 2 -C 6 alkyl-O—C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy C 2 -C 6 alkyl, —C(O)R9 and —SO 2 R9, or R7 and R8 combine to form (III), (IV); W is selected from CR1O and CR15, R1O is selected from H, halo, —C(O)NR13R14, C 1 -C 6 alkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, C 1 -C 6 alkylheteroaryl, C 1 -C 6 alkyl-O—C 1 -C 6 alkyl and hydroxy C 1 -C 6 alkyl; Het is a N-linked 5-membered heteroaryl ring optionally substituted with 1-3 substituents selected from methoxy, Cl, F, CH 3 , CF 3 , aryl, heteroaryl, C 1 -C 4 alkylaryl or C 1 -C 4 alkylheteroaryl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.

  本发明涉及以下式(I)的化合物或其药学上可接受的盐;其中A为(II);X选自CH、CF和N，R8选自H、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C2-C6烷基-O-C1-C6烷基、C1-C6卤代烷基、羟基C2-C6烷基、-C（O）R9和-SO2R9，或R7和R8结合形成(III)、(IV);W选自CR1O和CR15，R1O选自H、卤、-C（O）NR13R14、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C1-C6烷基-O-C1-C6烷基和羟基C1-C6烷基;Het是一种N-连接的5-成员杂环芳基环，可选地被1-3个取代基所取代，所述取代基选自甲氧基、Cl、F、CH3、CF3、芳基、杂环芳基、C1-C4烷基芳基或C1-C4烷基杂环芳基，用作DPP-IV酶的抑制剂，治疗或预防包括II型糖尿病在内的疾病。
• 1-amino linked compounds
  申请人：Eli Lilly and Company

  公开号：US08106090B2

  公开（公告）日：2012-01-31

  The present invention is directed to compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein A is (II); X is selected from CH, CF and N, R8 is selected from H, C1-C6 alkyl, aryl, heteroaryl, C1-C6 alkylaryl, C1-C6 alkylheteroaryl, C2-C6 alkyl-O—C1-C6 alkyl, C1-C6 haloalkyl, hydroxy C2-C6 alkyl, —C(O)R9 and —SO2R9, or R7 and R8 combine to form (III), (IV); W is selected from CR1O and CR15, R1O is selected from H, halo, —C(O)NR13R14, C1-C6 alkyl, aryl, heteroaryl, C1-C6 alkylaryl, C1-C6 alkylheteroaryl, C1-C6 alkyl-O—C1-C6 alkyl and hydroxy C1-C6 alkyl; Het is a N-linked 5-membered heteroaryl ring optionally substituted with 1-3 substituents selected from methoxy, Cl, F, CH3, CF3, aryl, heteroaryl, C1-C4 alkylaryl or C1-C4 alkylheteroaryl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.

  本发明涉及式(I)的化合物或其药学上可接受的盐；其中A为(II)；X选自CH、CF和N，R8选自H、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C2-C6烷基-O-C1-C6烷基、C1-C6卤代烷基、羟基C2-C6烷基、-C(O)R9和-SO2R9，或R7和R8结合形成(III)、(IV)；W选自CR1O和CR15，R1O选自H、卤素、-C(O)NR13R14、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C1-C6烷基-O-C1-C6烷基和羟基C1-C6烷基；Het是一种N-连接的5-成员杂环芳基环，可选地被1-3个取代基所取代，所述取代基选自甲氧基、Cl、F、CH3、CF3、芳基、杂环芳基、C1-C4烷基芳基或C1-C4烷基杂环芳基，用作DPP-IV酶抑制剂，用于治疗或预防包括II型糖尿病在内的疾病。
• 1-AMINO LINKED COMPOUNDS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1910317A1

  公开（公告）日：2008-04-16
• US8106090B2
  申请人：——

  公开号：US8106090B2

  公开（公告）日：2012-01-31
• [EN] 1-AMINO LINKED COMPOUNDS<br/>[FR] COMPOSÉS JOINTS EN POSITION 1-AMINO
  申请人：LILLY CO ELI

  公开号：WO2007015805A1

  公开（公告）日：2007-02-08

  [EN] The present invention is directed to compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein A is (II); X is selected from CH, CF and N, R8 is selected from H, C₁-C₆ alkyl, aryl, heteroaryl, C₁-C₆ alkylaryl, C₁-C₆ alkylheteroaryl, C₂-C₆ alkyl-O- C₁-C₆ alkyl, C₁-C₆ haloalkyl, hydroxy C₂-C₆ alkyl, -C(O)R9 and -SO₂R9, or R7 and R8 combine to form (III), (IV); W is selected from CRlO and CR15, RlO is selected from H, halo, -C(O)NR13R14, C₁-C₆ alkyl, aryl, heteroaryl, C₁-C₆ alkylaryl, C₁-C₆ alkylheteroaryl, C₁-C₆ alkyl-O- C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl; Het is a N-linked 5-membered heteroaryl ring optionally substituted with 1-3 substituents selected from methoxy, Cl, F, CH₃, CF₃, aryl, heteroaryl, C₁-C₄ alkylaryl or C₁-C₄ alkylheteroaryl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.
  [FR] La présente invention a pour objet des composés de formule (I) : ou un sel de qualité pharmaceutique desdits composés ; où A représente (II); X est sélectionné parmi CH, CF et N, R8 est sélectionné parmi H et les groupements alkyle en C₁-C₆, aryle, hétéroaryle, alkylaryle en C₁-C₆, alkylhétéroaryle en C₁-C₆, (alkyle en C₂-C₆)-O-(alkyle en C₁-C₆), halogénoalkyle en C₁-C₆, hydroxyalkyle en C₂-C₆, -C(O)R9 et -SO₂R9, ou R7 et R8 sont combinés pour former (III), (IV) ; W est sélectionné parmi CR10 et CR15, R10 est sélectionné parmi H et les groupements halogéno, -C(O)NR13R14, alkyle en C₁-C₆, aryle, hétéroaryle, alkylaryle en C₁-C₆, alkylhétéroaryle en C₁-C₆, (alkyle en C₁-C₆)-O-(alkyle en C₁-C₆) et hydroxyalkyle en C₁-C₆ ; Het est un hétérocycle aromatique à 5 chaînons joint au niveau du N et éventuellement substitué par 1 à 3 substituants sélectionnés parmi les groupements méthoxy, Cl, F, CH₃, CF₃, aryle, hétéroaryle, alkylaryle en C₁-C₄ et alkylhétéroaryle en C₁-C₄, qui peuvent être employés en tant qu'inhibiteurs de l'enzyme DPP-IV dans le traitement prophylactique ou thérapeutique d'états pathologiques incluant le diabète de Type II.