4-cyclohexyl-1-butanamine hydrochloride | 91342-30-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-cyclohexyl-1-butanamine hydrochloride
• 英文别名: 4-cyclohexylbutylamine hydrochloride；4-cyclohexylbutan-1-amine hydrochloride；4-cyclohexylbutanamine hydrochloride；4-cyclohexylbutyl amine hydrochloride salt；4-cyclohexylbutyl ammonium chloride；4-Cyclohexylbutan-1-amine;hydrochloride
• CAS: 91342-30-2
• 化学式: C₁₀H₂₁N*ClH
• 分子量: 191.744
• InChiKey: HJSBKANKLRDTKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.02
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  27.6
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-cyclohexyl-1-butanamine hydrochloride 在 N-甲基吗啉 、 nickel(IV) oxide 、 sodium hydroxide 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 4.0h， 生成 [1S-(1α,2α,3α,4α)-2-[[3-[4-[(Cyclohexylbutyl)-amino]carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2.1]-hept-2-yl]methyl]benzoic acid
  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-phenylbutylamine hydrochloride 在 Rh on carbon 氢气 作用下， 以 乙醇 为溶剂， 反应 20.0h， 以100%的产率得到4-cyclohexyl-1-butanamine hydrochloride
  参考文献：
  名称：

  Synthesis and histamine H2 agonistic activity of arpromidine analogues: replacement of the pheniramine-like moiety by non-heterocyclic groups

  摘要：

  Analogues of the potent histamine H-2 agonist arpromidine, characterized by non-heterocyclic groups (phenyl, cyclo-hexyl, alkyl) instead of the pheniramine-like portion, were prepared and tested for their H-2 agonistic and H-1 antagonistic activity in the isolated guinea pig right atrium and ileum, respectively. In the diphenylpropylguanidine series an increase in H-2 agonistic potency resulted from mono- or difluorination at one or both phenyl rings in the meta and/or para position (pD2 less-than-or-equal-to 7.75 vs pD2 = 7.15 for the unsubstituted parent compound). Compounds chlorinated at both phenyl rings were considerably less potent. Highest combined H-2 agonistic/H-1 antagonistic potency was found in the 4-fluorophenyl series. The arpromidine analogue with cyclohexyl and methyl group instead of phenyl and pyridine ring proved to be 30 times more potent than histamine in the atrium. The H-1 antagonistic potency in cyclohexyl compounds was lower than in the diaryl series. Thus, aromatic rings appear not to be required for high H-2 agonistic potency but are useful for combined H-2 agonistic/H-1 antagonistic activity.

  DOI：

  10.1016/0223-5234(92)90145-q

文献信息

• Bis-heterocyclic prostaglandin analogs
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05280034A1

  公开（公告）日：1994-01-18

  Thromboxane receptor antagonist activity is exhibited by compounds of the formula ##STR1## wherein: W is --(CH.sub.2).sub.m -- or ##STR2## but if R.sup.3 and R.sup.4 complete an aromatic ring, then W cannot be ##STR3## X is --(CH.sub.2).sub.2 --, --CH.dbd.CH-- or phenylene; Y is --O--, a single bond or vinylene, except that Y cannot be --O-- when n is 0, and if Y is vinylene, then n must be 0; Z is O or NH; R.sup.3 and R.sup.4 are each independently hydrogen, alkyl, alkenyl, or alkynyl, or R.sup.3 and R.sup.4 together complete a ring as defined in the specification, optionally substituted through a ring carbon with an oxo or hydroxyl group; and the remaining symbols are as defined in the specification.

  血栓素受体拮抗活性由以下式的化合物展示：其中：W为--(CH.sub.2).sub.m --或##STR2##但如果R.sup.3和R.sup.4组成芳香环，则W不能为##STR3##X为--(CH.sub.2).sub.2 --，--CH.dbd.CH--或苯亚甲基；Y为--O--，单键或乙烯基，但当n为0时，Y不能为--O--，如果Y为乙烯基，则n必须为0；Z为O或NH；R.sup.3和R.sup.4分别为氢、烷基、烯基或炔基，或R.sup.3和R.sup.4一起组成如规范中定义的环，通过环碳可选择地被氧代或羟基取代；其余符号如规范中定义。
• Prostaglandin analogs
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05827868A1

  公开（公告）日：1998-10-27

  Thromboxane receptor antagonist activity is exhibited by compounds of the formula ##STR1## wherein: V is --(CH.sub.2).sub.m --, --O--, or ##STR2## but if V is --O--or ##STR3## R.sup.3 and R.sup.4 must complete an aromatic ring; W is --(CH.sub.2).sub.2 --, --CH.dbd.CH-- or phenylene; X is a single bond, --CH.dbd.CH--, --(CH.sub.2).sub.n --, or --O--(CH.sub.2).sub.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 --CO.sub.2 H, --CO.sub.2 alkyl, --CO.sub.2 alkali metal, --CH.sub.2 OH, --CONHSO.sub.2 R.sup.5, --CONHR.sup.6, or --CH.sub.2 -5-tetrazolyl; Z is O or NH; R.sup.3 and R.sup.4 are each independently hydrogen or alkyl or R.sup.3 and R.sup.4 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.

  血栓素受体拮抗活性由以下式的化合物展示：##STR1## 其中：V为--(CH.sub.2).sub.m --，--O--，或##STR2## 但如果V为--O--或##STR3##，则R.sup.3和R.sup.4必须形成一个芳香环；W为--(CH.sub.2).sub.2 --，--CH.dbd.CH--或苯基；X为单键，--CH.dbd.CH--，--(CH.sub.2).sub.n --，或--O--(CH.sub.2).sub.n --；或X为支链烷基或--O--支链烷基，其中W通过一个含有n个碳原子的链连接到Y；Y为--CO.sub.2 H，--CO.sub.2 烷基，--CO.sub.2 碱金属，--CH.sub.2 OH，--CONHSO.sub.2 R.sup.5，--CONHR.sup.6，或--CH.sub.2 -5-四唑基；Z为O或NH；R.sup.3和R.sup.4分别独立地为氢或烷基，或R.sup.3和R.sup.4一起形成一个环，该环可以通过一个含有卤素、低烷基、苯基、卤代(低烷基)、卤代苯基、氧代或羟基基团的环碳原子进行选择性取代；其余符号如规范中定义。
• Anti-thrombotic heterocyclic amido prostaglandin analogs
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05126370A1

  公开（公告）日：1992-06-30

  Prostaglandin analogs useful in treating thrombotic and vasospastic disease having the structural formula ##STR1## wherein: m is 1, 2 or 3: n is 1, 2 or 3, except that n is O when Y is vinylene; p is 1, 2 or 3; R is CO.sub.2 R', CH.sub.2 OH, CONHSO.sub.2 R.sup.3, CONHR.sup.4, or --CH.sub.2 -5-tetrazolyl; R' is hydrogen, alkyl, or alkali metal; Y is --O--, a single bond or vinylene, except that Y cannot be --O-- when n is 0; and the remaining symbols are as defined in the specification.

  前列腺素类似物在治疗血栓性和血管痉挛性疾病中有用，其结构式为##STR1##其中：m为1、2或3；n为1、2或3，但当Y为乙烯基时，n为O；p为1、2或3；R为CO.sub.2 R'、CH.sub.2 OH、CONHSO.sub.2 R.sup.3、CONHR.sup.4或--CH.sub.2 -5-四唑基；R'为氢、烷基或碱金属；Y为--O--、单键或乙烯基，但当n为0时，Y不能为--O--；其余符号如规范中所定义。
• 7-oxabicycloheptyl substituted heterocyclic thioamide prostaglandin
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05290799A1

  公开（公告）日：1994-03-01

  7-Oxabicycloheptane substituted prostaglandin analogs useful in treating thrombotic and vasospastic disease have the structural formula ##STR1## wherein m is 1, 2 or 3; n is 1, 2, 3 or 4; Z is --(CH.sub.2).sub.2 --, --CH.dbd.CH-- or ##STR2## wherein Y is O, a single bond or vinyl, with the proviso that when n is O, if Z is ##STR3## then Y cannot be O, and when Z is --CH.dbd.CH--, n is 1, 2, 3 or 4; and when Y=vinyl, n=0; R is CO.sub.2 H, CO.sub.2 lower alkyl, CH.sub.2 OH, CO.sub.2 alkali metal, CONHSOR.sup.3, CONHR.sup.3a or --CH.sub.2 -5-tetrazolyl, X is O, S or NH; and where R.sup.1, R.sup.2, R.sup.3 and R.sup.3a are as defined herein.

  7-氧杂双环庚烷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具有有用的结构式##STR1##其中m为1、2或3；n为1、2、3或4；Z为--(CH.sub.2).sub.2 --，--CH.dbd.CH--或##STR2##其中Y为O、单键或乙烯基，但要注意当n为O时，如果Z为##STR3##则Y不能为O，当Z为--CH.dbd.CH--时，n为1、2、3或4；当Y=乙烯基时，n=0；R为CO.sub.2 H、CO.sub.2 较低烷基、CH.sub.2 OH、CO.sub.2 碱金属、CONHSOR.sup.3、CONHR.sup.3a或--CH.sub.2 -5-四唑基，X为O、S或NH；其中R.sup.1、R.sup.2、R.sup.3和R.sup.3a如本文所定义。
• Substituted stryl heterocyclic amido prostaglandin analogs
  申请人：E.R. Squibb & Sons, Inc.

  公开号：US05550248A1

  公开（公告）日：1996-08-27

  Prostaglandin analogs useful in treating thrombotic and vasospastic disease having the structural formula ##STR1## wherein: C.sub.m H.sub.p is an alkylene chain wherein m is 0, 1, 2, or 3 and p=(2.times.m)-1, except that when m is 0, p is also 0; n is 0, 1, 2 or 3; R is CO.sub.2 R', CH.sub.2 OH, CONHSO.sub.2 R.sup.3, CONHR.sup.4, or --CH.sub.2 --5--tetrazolyl; R' is hydrogen, alkyl, or alkali metal; X is O or NH; Y is --O--, a single bond or vinylene, except that Y cannot be --O-- when n is 0; and the remaining symbols are as defined in the specification.

  前列腺素类似物在治疗血栓性和血管痉挛性疾病中有用，具有结构式##STR1##其中：C.sub.m H.sub.p是一个烷基链，其中m为0、1、2或3，p=(2×m)-1，但当m为0时，p也为0；n为0、1、2或3；R为CO.sub.2 R'、CH.sub.2 OH、CONHSO.sub.2 R.sup.3、CONHR.sup.4或--CH.sub.2 --5--tetrazolyl；R'为氢、烷基或碱金属；X为O或NH；Y为--O--、单键或乙烯基，但当n为0时，Y不能为--O--；其余符号如规范中定义。