(3R)-3-(Benzyloxycarbonylamino)-4-t-butoxycarbonyl-butyraldehyde Diethyl Acetal | 215596-32-0

• 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: (3R)-3-(Benzyloxycarbonylamino)-4-t-butoxycarbonyl-butyraldehyde Diethyl Acetal
• 英文别名: tert-butyl (3R)-5,5-diethoxy-3-(phenylmethoxycarbonylamino)pentanoate
• CAS: 215596-32-0
• 化学式: C₂₁H₃₃NO₆
• 分子量: 395.496
• InChiKey: ZOFQSHZHXOTWSN-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R)-3-(Benzyloxycarbonylamino)-4-t-butoxycarbonyl-butyraldehyde Diethyl Acetal 在 palladium-carbon 作用下， 以 乙醇 为溶剂， 生成 tert-butyl (R)-3-amino-5,5-diethoxypentanoate
  参考文献：
  名称：

  (3R)-3-amino-4-carboxybutyraldehyde derivatives inhibiting the release of interleukin-1/beta

  摘要：

  该发明涉及一种新的通式(I)的(3R)-3-氨基-4-羧基丁醛衍生物，其中X代表C1-4烷氧羰基，可选择性取代的苯基-(C1-2烷氧)-羰基，C1-4烷基羰基或可选择性取代的苯基-(C1-3烷基)-羰基，n代表1或0，Y代表当n=1时的四肽通式Y4-Y3-Y2-Y1，三肽通式Y3-Y2-Y1或二肽通式Y2-Y1或氨基酸残基通式Y1，或者当n=0时，α-羟基酰三肽通式Q4-Y3-Y2-Y1，α-羟基酰二肽通式Q3-Y2-Y1或α-羟基酰-氨基酰残基通式Q2-Y1；其中Y1-Y4代表从以下L-或D-氨基酸组中选择的残基：丙氨酸、异亮氨酸、环己基甘氨酸、苯丙氨酸、谷氨酰胺、组氨酸、异亮氨酸、亮氨酸、赖氨酸、蛋氨酸、环戊胺基乙酸、脯氨酸、酪氨酸和缬氨酸；Q2-Q4代表从以下R或S构型的α-羟基酸中选择的酰基：2-环庚基-2-羟基乙酸、2-环己基-2-羟基乙酸、3-环己乳酸、3-苯乳酸、2-羟基-3-甲基丁酸、2-羟基-3-甲基戊酸、苹果酸或乳酸，以及与有机或无机碱形成的盐，以及含有这些化合物的药物组合物。该发明的通式(I)化合物是有价值的白细胞介素-1β转化酶的抑制剂。

  公开号：

  US06593300B1
• 作为产物：
  描述：

  Z-Asp(OBut)-CHN2 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 氢气 、 silver(l) oxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (3R)-3-(Benzyloxycarbonylamino)-4-t-butoxycarbonyl-butyraldehyde Diethyl Acetal
  参考文献：
  名称：

  Peptidyl β-homo-aspartals: Specific inhibitors of interleukin-1β converting enzyme and its homologues (caspases)

  摘要：

  Inhibition of interleukin-1 beta converting enzyme (ICE), apopain, papain, thrombin and trypsin with substrate like peptidyl L- and D-alpha-aldehydes and their L-beta-homo-aldehyde analogues was investigated. The L-beta-homo-aspartals appear to be specific inhibitors for ICE and its homologues; the other enzymes were not inhibited with such L-beta-homo aldehydes. Papain shows tolerance for D-residues at P-1 depending on their chiral stability. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00244-3

文献信息

• (3R)-3-amino-4-carboxybutyraldehyde derivatives inhibiting the release of interleukin-1/beta
  申请人：Gyogyszerkutato Intezet Kft.

  公开号：US06593300B1

  公开（公告）日：2003-07-15

  The invention relates to a new (3R)-3-amino-4-carboxybutyraldehyde derivatives of general formula(I) wherein X represents a C1-4 alkyloxycarbonyl, an optionally substituted phenyl-(C1-2 alkyloxy)-carbonyl, a C1-4 alkylcarbonyl or an optionally substituted phenyl-(C1-3 alkyl)-carbonyl group, n represents 1 or 0, Y represents, in the case when n=1, a tetrapeptide of general formula Y4-Y3-Y2-Y1, a tripeptide of general formula Y3-Y2-Y1 or a dipeptide of general formula Y2-Y1 or an amino acid residue of general formula Y1, or in the case when n=0, an &agr;-hydroxyacyl-tripeptide of general formula Q4-Y3-Y2-Y1, an &agr;-hydroxyacyl-dipeptide of general formula Q3-Y2-Y1 or an &agr;-hydroxyacyl-aminoacyl residue of general formula Q2-Y1; wherein Y1-Y4 represent a residue selected from the group of the following L- or D-amino acids: alanine, alloisoleucine, cyclohexyl-glycine, phenyl-alanine, glutamine, histidine, isoleucine, leucine, lysine, methionine, pipecolic acid, proline, tyrosine and valine; and Q2-Q4 represent an acyl group selected from the following &agr;-hydroxyacids of R or S configuration: 2-cycloheptyl-2-hydroxy-acetic acid, 2-cyclohexyl-2-hydroxyacetic acid, 3-cyclohexyllactic acid, 3-phenyllactic acid, 2-hydroxy-3-methylbutyric acid, 2-hydroxy-3-methylvaleric acid, mandelic acid or lactic acid, and salts thereof formed with organic or inorganic bases, and pharmaceutical compositions containing the same. The compounds of general formula (I) of the invention are valuable inhibitors of the interleukin-1&bgr; converting enzyme.

  该发明涉及一种新的通式(I)的(3R)-3-氨基-4-羧基丁醛衍生物，其中X代表C1-4烷氧羰基，可选择性取代的苯基-(C1-2烷氧)-羰基，C1-4烷基羰基或可选择性取代的苯基-(C1-3烷基)-羰基，n代表1或0，Y代表当n=1时的四肽通式Y4-Y3-Y2-Y1，三肽通式Y3-Y2-Y1或二肽通式Y2-Y1或氨基酸残基通式Y1，或者当n=0时，α-羟基酰三肽通式Q4-Y3-Y2-Y1，α-羟基酰二肽通式Q3-Y2-Y1或α-羟基酰-氨基酰残基通式Q2-Y1；其中Y1-Y4代表从以下L-或D-氨基酸组中选择的残基：丙氨酸、异亮氨酸、环己基甘氨酸、苯丙氨酸、谷氨酰胺、组氨酸、异亮氨酸、亮氨酸、赖氨酸、蛋氨酸、环戊胺基乙酸、脯氨酸、酪氨酸和缬氨酸；Q2-Q4代表从以下R或S构型的α-羟基酸中选择的酰基：2-环庚基-2-羟基乙酸、2-环己基-2-羟基乙酸、3-环己乳酸、3-苯乳酸、2-羟基-3-甲基丁酸、2-羟基-3-甲基戊酸、苹果酸或乳酸，以及与有机或无机碱形成的盐，以及含有这些化合物的药物组合物。该发明的通式(I)化合物是有价值的白细胞介素-1β转化酶的抑制剂。
• (3R)-3-AMINO-4-CARBOXYBUTYRALDEHYDE DERIVATIVES INHIBITING THE RELEASE OF INTERLEUKIN-1/BETA
  申请人：GYOGYSZERKUTATO INTEZET KFT.

  公开号：EP0979241A1

  公开（公告）日：2000-02-16
• US6593300B1
  申请人：——

  公开号：US6593300B1

  公开（公告）日：2003-07-15
• [EN] (3R)-3-AMINO-4-CARBOXYBUTYRALDEHYDE DERIVATIVES INHIBITING THE RELEASE OF INTERLEUKIN-1/BETA<br/>[FR] DERIVES DE (3R)-3-AMINO-4-CARBOXYBUTYRALDEHYDE INHIBANT LA LIBERATION D'INTERLEUKINE-1/BETA
  申请人：GYÓGYSZERKUTATÓ INTÉZET KFT.

  公开号：WO1998049189A1

  公开（公告）日：1998-11-05

  (EN) The invention relates to new (3R)-3-amino-4-carboxybutyraldehyde derivatives of general formula (I), wherein X represents a C1-4 alkyloxycarbonyl, an optionally substituted phenyl-(C1-2 alkyloxy)-carbonyl, a C1-4 alkylcarbonyl or an optionally substituted phenyl-(C1-3 alkyl)-carbonyl group, n represents 1 or 0, Y represents, in the case when n = 1, a tetrapeptide of general formula Y 4-Y3-Y2-Y1, a tripeptide of general formula Y3-Y2-Y1 or a dipeptide of general formula Y2-Y1 or an amino acid residue of general formula Y1, or in the case when n = 0, an $g(a)-hydroxyacyl-tripeptide of general formula Q4-Y3-Y2-Y1, an $g(a)-hydroxyacyl-dipeptide of general formula Q3-Y2-Y1 or an $g(a)-hydroxyacyl-aminoacyl residue of general formula Q2-Y1; wherein Y1-Y4 represent a residue selected from the group of the following L- or D-amino acids: alanine, alloisoleucine, cyclohexyl-glycine, phenyl-alanine, glutamine, histidine, isoleucine, leucine, lysine, methionine, pipecolic acid, proline, tyrosine and valine; and Q2-Q4 represent an acyl group selected form the following $g(a)-hydroxyacids of R or S configuration: 2-cycloheptyl-2-hydroxy-acetic acid, 2-cyclohexyl-2-hydroxyacetic acid, 3-cyclohexyllactic acid, 3-phenyllactic acid, 2-hydroxy-3-methylbutyric acid, 2-hydroxy-3-methylvaleric acid, mandelic acid or lactic acid, and salts thereof formed with organic or inorganic bases, and pharmaceutical compositions containing the same. The compounds of general formula (I) of the invention are valuable inhibitors of the interleukin-1$g(b) converting enzyme.(FR) L'invention concerne de nouveaux dérivés de (3R)-3-amino-4-carboxybutyraldehyde de formule générale (I), dans laquelle X représente un groupe alkyle oxycarbonyle C1-4, un groupe phényl-(alkyloxy C1-2)-carbonyle éventuellement substitué, un groupe alkylcarbonyle C1-4 ou bien un groupe phényl-(alkyl C1-3)-carbonyle éventuellement substitué, n vaut 1 ou 0, Y représente, dans le cas où n = 1, un tétrapeptide de formule générale Y4-Y3-Y2-Y1, un tripeptide de formule générale Y3-Y2-Y1 ou bien un dipeptide de formule générale Y 2-Y1 ou encore un résidu aminoacide de formule générale Y1, ou bien dans le cas où n = 0, un tripeptide d'$g(a)-hydroxyacyle de formule générale Q4-Y3-Y2-Y1, un dipeptide d'$g(a)-hydroxyacyle de formule générale Q3-Y2-Y1 ou bien un résidu $g(a)-hydroxyacyl-aminoacyle de formule générale Q2-Y1, où Y1-Y4 représentent un résidu choisi dans le groupe des acides aminés L ou D suivants: alanine, alloisoleucine, cyclohexyl-glycine, phényl-alanine, glutamine, histidine, isoleucine, leucine, lysine, méthionine, acide pipécolique, proline, tyrosine et valine, et Q2-Q4 représentent un groupe acyle choisi parmi les $g(a)-hydroxyacides de configuration R ou S suivants: acide 2-cycloheptyl-2-hydroxyacétique, acide 2-cyclohexyl-2-hydroxyacétique, acide 3-cyclohexyllactique, acide 3-phényllactique, acide 2-hydroxy-3-méthylbutyrique, acide 2-hydroxy-3-méthylvalérique, acide mandélique ou acide lactique, ainsi que leurs sels formés avec des bases organiques ou inorganiques, et des compositions pharmaceutiques les contenant. Les composés de formule générale (I) sont de précieux inhibiteurs de l'enzyme de conversion de l'interleukine-1$g(b).
• Peptidyl β-homo-aspartals: Specific inhibitors of interleukin-1β converting enzyme and its homologues (caspases)
  作者：Sándor Bajusz、Irén Fauszt、Klára Németh、Éva Barabás、Attila Juhász、Miklós Patthy

  DOI：10.1016/s0960-894x(98)00244-3

  日期：1998.6

  Inhibition of interleukin-1 beta converting enzyme (ICE), apopain, papain, thrombin and trypsin with substrate like peptidyl L- and D-alpha-aldehydes and their L-beta-homo-aldehyde analogues was investigated. The L-beta-homo-aspartals appear to be specific inhibitors for ICE and its homologues; the other enzymes were not inhibited with such L-beta-homo aldehydes. Papain shows tolerance for D-residues at P-1 depending on their chiral stability. (C) 1998 Elsevier Science Ltd. All rights reserved.