N-(4-cyclohexylbutyl)-L-serinamide | 130776-17-9

• 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: N-(4-cyclohexylbutyl)-L-serinamide
• 英文别名: N-(4-cyclohexyl-butyl)-L-serinamide；(2S)-2-amino-N-(4-cyclohexylbutyl)-3-hydroxypropanamide
• CAS: 130776-17-9
• 化学式: C₁₃H₂₆N₂O₂
• 分子量: 242.362
• InChiKey: QIUSDQZLXRDMQG-LBPRGKRZSA-N

物化性质

• 沸点：
  468.9±35.0 °C(Predicted)
• 密度：
  1.035±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-cyclohexylbutyl)-L-serinamide 在 N-甲基吗啉 、 lithium hydroxide 、 potassium carbonate 、 1-羟基苯并三唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 copper(ll) bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 52.17h， 生成 SQ 33961
  参考文献：
  名称：

  Interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles. Highly potent, selective, and long-acting thromboxane A2 receptor antagonists

  摘要：

  A series of interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles (2) were prepared and evaluated for their thromboxane (TxA2) antagonistic activity in vitro and duration of action in vivo. Examination of the carboxyl side chain indicated that the interphenylene ring substitution pattern and, to a lesser extent, chain length were important factors in determining TxA2 antagonistic potency. For the carboxyl side chain, ortho substitution, a single methylene spacer between the interphenylene and oxabicycloheptane rings, and a propionic acid side-chain length were determined to be optimal. With respect to the oxazole side chain a wide range of amide substituents with diverse structures and lipophilicities were compatible with potent antagonistic activity. Finally. an acidic functional group on the alpha-chain and a hydrogen bond acceptor on the 4-position of the oxazole ring were critical for potent activity. From the analogs prepared 42 {BMS-180,291: [(+)-1S-(1alpha,2alpha,3alpha,4alpha)]-2-[[3-[4-[(n-pentylamino)carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl]benzenepropanoic acid} was found to be a potent, selective, and orally-active TxA2 antagonist with a long duration of action and has been selected as a candidate for clinical development. In human platelet-rich plasma, 42 inhibited arachidonic acid (800 muM) and U-46,619 (10 muM) induced aggregation with I50 values of 7 and 21 nM, respectively. Radioligand binding studies of 42 with [H-3]-SQ 29,548 showed a K(d) value of 4.0 +/- 1.0 nM in human platelet membranes. Both in vitro and in vivo studies indicated 42 was devoid of direct agonistic activity. In vivo 42 (0.2 mg/kg, po) showed extended protection (T50 = 14.4 h) from U-46,619 (2 mg/kg, iv) induced death in mice, and a single oral dose of 42 (3 mg/kg) abolished U46,619-induced platelet aggregation ex vivo in African green monkeys for >24 h.

  DOI：

  10.1021/jm00062a013
• 作为产物：
  描述：

  4-cyclohexyl-1-butanamine hydrochloride 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-(4-cyclohexylbutyl)-L-serinamide
  参考文献：
  名称：

  Interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles. Highly potent, selective, and long-acting thromboxane A2 receptor antagonists

  摘要：

  A series of interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles (2) were prepared and evaluated for their thromboxane (TxA2) antagonistic activity in vitro and duration of action in vivo. Examination of the carboxyl side chain indicated that the interphenylene ring substitution pattern and, to a lesser extent, chain length were important factors in determining TxA2 antagonistic potency. For the carboxyl side chain, ortho substitution, a single methylene spacer between the interphenylene and oxabicycloheptane rings, and a propionic acid side-chain length were determined to be optimal. With respect to the oxazole side chain a wide range of amide substituents with diverse structures and lipophilicities were compatible with potent antagonistic activity. Finally. an acidic functional group on the alpha-chain and a hydrogen bond acceptor on the 4-position of the oxazole ring were critical for potent activity. From the analogs prepared 42 {BMS-180,291: [(+)-1S-(1alpha,2alpha,3alpha,4alpha)]-2-[[3-[4-[(n-pentylamino)carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl]benzenepropanoic acid} was found to be a potent, selective, and orally-active TxA2 antagonist with a long duration of action and has been selected as a candidate for clinical development. In human platelet-rich plasma, 42 inhibited arachidonic acid (800 muM) and U-46,619 (10 muM) induced aggregation with I50 values of 7 and 21 nM, respectively. Radioligand binding studies of 42 with [H-3]-SQ 29,548 showed a K(d) value of 4.0 +/- 1.0 nM in human platelet membranes. Both in vitro and in vivo studies indicated 42 was devoid of direct agonistic activity. In vivo 42 (0.2 mg/kg, po) showed extended protection (T50 = 14.4 h) from U-46,619 (2 mg/kg, iv) induced death in mice, and a single oral dose of 42 (3 mg/kg) abolished U46,619-induced platelet aggregation ex vivo in African green monkeys for >24 h.

  DOI：

  10.1021/jm00062a013

文献信息

• Prostamide receptor antagonists
  申请人：Allergan, Inc.

  公开号：US07868032B2

  公开（公告）日：2011-01-11

  The present invention provides prostamide receptor antagonist compounds that may be represented by the general formula I wherein A, R1, R2, R3, R4 and R6 are as defined in the specification.

  本发明提供了可能由一般公式I表示的前列腺酰胺受体拮抗剂化合物，其中A、R1、R2、R3、R4和R6如规范中定义。
• Gem-dialkyl-7-oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs useful in the treatment of thrombotic and vasospastic disease
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0544287A1

  公开（公告）日：1993-06-02

  Gem-dialkyl-7-oxabicycloheptane substituted prostaglandin analogs useful in treating thrombotic and vasospastic disease have the structural formula wherein m is 1, 2 or 3; n is 0, 1, 2, 3 or 4; Z is -(CH₂)₂-, -CH=CH- or with the proviso when Z is -CH=CH-, n is l, 2, 3 or 4; R is CO₂H, CO₂lower alkyl, or CO₂alkali metal, X is O or NH; and where R¹ and R² are as defined herein and R³ and R⁴ are each independently alkyl, or R³ and R⁴ may be taken together with the carbon to which it is attached to form a 3- or 4-membered ring.

  Gem-二烷基-7-氧杂双环庚烷基取代前列腺素类似物在治疗血栓性和血管痉挛性疾病方面有用，其结构式为m为1、2或3；n为0、1、2、3或4；Z为-(CH₂)₂-，-CH=CH-或者在Z为-CH=CH-时，n为1、2、3或4；R为CO₂H、CO₂较低烷基，或CO₂碱金属，X为O或NH；其中R¹和R²如上所定义，R³和R⁴各自独立为烷基，或R³和R⁴可以与其附着的碳一起形成3-或4-成员环。
• 7-Oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs useful in the treatment of thrombotic and vasospastic disease
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0374952A2

  公开（公告）日：1990-06-27

  7-Oxabicycloheptane substituted prostaglandin analogs which are thromboxane A2 (TxA2) receptor antagonists or combined thromboxane A2 receptor antagonists/thromboxane synthase inhibitors useful, for example, in treating thrombotic and vasospastic disease have the structural formula wherein m is 1, 2 or 3; n is 0, 1, 2, 3 or 4; Z is -(CH2)2- or -CH=CH-, with the proviso when Z is -CH = CH-, n is 1, 2, 3 or 4; R is C02H, CO2lower alkyl, CH2OH, CO2alkali metal, CONHSOR3, CONHR3a or -CH2-5-tetrazolyl, X is 0, S or NH; and where R1, R2, R3 and R3a are as defined herein.

  7-氧杂双环庚烷取代的前列腺素类似物是血栓素 A2（TxA2）受体拮抗剂或血栓素 A2 受体拮抗剂/血栓素合成酶联合抑制剂，可用于治疗血栓性疾病和血管痉挛性疾病等，其结构式为 其中 m 是 1、2 或 3；n 是 0、1、2、3 或 4；Z 是-(CH2)2- 或-CH=CH-，但当 Z 是-CH=CH-时，n 是 1、2、3 或 4；R 是 C02H、CO2lower 烷基、CH2OH、CO2 碱金属、CONHSOR3、CONHR3a 或-CH2-5-四唑基，X 是 0、S 或 NH；其中 R1、R2、R3 和 R3a 如本文所定义。
• 7-Oxabicycloheptyl substituted heterocyclic thioamide prostaglandin analogs useful in the treatment of thrombotic and vasospastic disease
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0476994A1

  公开（公告）日：1992-03-25

  7-Oxabicycloheptane substituted prostaglandin analogs useful in treating thrombotic and vasospastic disease have the structural formula wherein m is 1, 2 or 3; n is 1, 2, 3 or 4; Z is -(CH₂)₂-, -CH=CH- or wherein Y is O, a single bond or vinyl, with the proviso that when n is O, if Z is then Y cannot be O, and when Z is -CH=CH-, n is 1, 2, 3 or 4; and when Y=vinyl, n=0; R is CO₂H, CO₂lower alkyl, CH₂OH, CO₂alkali metal, CONHSOR³, CONHR3a or -CH₂-5-tetrazolyl, X is O, S or NH; and where R¹, R², R³ and R3a are as defined herein.

  可用于治疗血栓性和血管痉挛性疾病的 7-氧杂双环庚烷取代的前列腺素类似物的结构式为 其中 m 是 1、2 或 3；n 是 1、2、3 或 4；Z 是-(CH₂)₂-、-CH=CH- 或-(CH₂)₂-。 其中 Y 是 O、单键或乙烯基，但当 n 是 O 时，如果 Z 是 则 Y 不能为 O，当 Z 为-CH=CH-时，n 为 1、2、3 或 4；当 Y= 乙烯基时，n=0；R 为 CO₂H、CO₂低级烷基、CH₂OH、CO₂碱金属、CONHSOR³、CONHR3a 或-CH₂-5-四唑基，X 为 O、S 或 NH；其中 R¹、R²、R³ 和 R3a 如本文所定义。
• Oxazole and imidazole derivatives as prostaglandin analogs
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0536713A1

  公开（公告）日：1993-04-14

  Thromboxane receptor antagonist activity is exhibited by compounds of the formula wherein:    V is -(CH₂)m-, -O-, or but if V is -O- or R³ and R⁴ must complete an aromatic ring;    W is -(CH₂)₂-, -CH=CH- or phenylene;    X is a single bond, -CH=CH-, -(CH₂)n-, or -O-(CH₂)n-; or X is branched alkylene or -O-branched alkylene wherein W is linked to Y through a chain n carbon atoms long;    Y is -CO₂H, -CO₂alkyl, -CO₂alkali metal, -CH₂OH, -CONHSO₂R⁵, -CONHR⁶, or -CH₂-5-tetrazolyl;    Z is O or NH;    R³ and R⁴ are each independently hydrogen or alkyl or R³ and R⁴ together complete a ring optionally substituted through a ring carbon with a halo, lower alkyl, phenyl, halo (lower alkyl), halophenyl, oxo or hydroxyl group; and the remaining symbols are as defined in the specification.

  式中化合物具有血栓素受体拮抗剂活性 其中 V 是-(CH₂)m-、-O-或 但如果 V 是 -O- 或 R³ 和 R⁴ 必须是完整的芳香环； W 是-(CH₂)₂-、-CH=CH-或亚苯基； X 是单键、-CH=CH-、-(CH₂)n- 或-O-(CH₂)n-；或 X 是支链亚烷基或-O-支链亚烷基，其中 W 通过 n 个碳原子长的链与 Y 连接； Y 是-CO₂H、-CO₂烷基、-CO₂碱金属、-CH₂OH、-CONHSO₂R⁵、-CONHR⁶或-CH₂-5-四唑基； Z 是 O 或 NH； R³ 和 R⁴ 各自独立地为氢或烷基，或 R³ 和 R⁴ 共同组成一个环，可通过环碳任选被卤代、低级烷基、苯基、卤代（低级烷基）、卤代苯基、氧代或羟基取代；其余符号如说明书中所定义。