5-Propyl-3-isoxazolecarbonyl chloride | 53064-55-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-Propyl-3-isoxazolecarbonyl chloride
• 英文别名: 5-propyl-1,2-oxazole-3-carbonyl chloride
• CAS: 53064-55-4
• 化学式: C₇H₈ClNO₂
• 分子量: 173.599
• InChiKey: GDDDZAGDMAFFJZ-UHFFFAOYSA-N

物化性质

• 沸点：
  264.2±28.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-Propyl-3-isoxazolecarbonyl chloride 、 N-环戊基环己胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-cyclohexyl-N-cyclopentyl-5-propyl-1,2-oxazole-3-carboxamide
  参考文献：
  名称：

  Discovery, design and synthesis of a selective S1P3 receptor allosteric agonist

  摘要：

  Potent and selective S1P(3) receptor (S1P(3)-R) agonists may represent important proof-of-principle tools used to clarify the receptor biological function and assess the therapeutic potential of the S1P(3)-R in cardiovascular, inflammatory and pulmonary diseases. N, N-Dicyclohexyl-5-propylisoxazole-3-carboxamide was identified by a high-throughput screening of MLSMR library as a promising S1P(3)-R agonist. Rational chemical modifications of the hit allowed the identification of N, N-dicyclohexyl-5-cyclopropylisoxazole-3-carboxamide, a S1P(3)-R agonist endowed with submicromolar activity and exquisite selectivity over the remaining S1P(1,2,4,5)-R family members. A combination of ligand competition, site-directed mutagenesis and molecular modeling studies showed that the N, N-dicyclohexyl-5-cyclopropylisoxazole-3-carboxamide is an allosteric agonist and binds to the S1P(3)-R in a manner that does not disrupt the S1P(3)-R-S1P binding. The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the molecular basis of the receptor function, and provides the bases for further rational design of more potent and drug-like S1P(3)-R allosteric agonists. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.075
• 作为产物：
  描述：

  5-丙基-异恶唑-3-羧酸 在 氯化亚砜 作用下， 以 苯 为溶剂， 反应 3.0h， 生成 5-Propyl-3-isoxazolecarbonyl chloride
  参考文献：
  名称：

  Discovery, design and synthesis of a selective S1P3 receptor allosteric agonist

  摘要：

  Potent and selective S1P(3) receptor (S1P(3)-R) agonists may represent important proof-of-principle tools used to clarify the receptor biological function and assess the therapeutic potential of the S1P(3)-R in cardiovascular, inflammatory and pulmonary diseases. N, N-Dicyclohexyl-5-propylisoxazole-3-carboxamide was identified by a high-throughput screening of MLSMR library as a promising S1P(3)-R agonist. Rational chemical modifications of the hit allowed the identification of N, N-dicyclohexyl-5-cyclopropylisoxazole-3-carboxamide, a S1P(3)-R agonist endowed with submicromolar activity and exquisite selectivity over the remaining S1P(1,2,4,5)-R family members. A combination of ligand competition, site-directed mutagenesis and molecular modeling studies showed that the N, N-dicyclohexyl-5-cyclopropylisoxazole-3-carboxamide is an allosteric agonist and binds to the S1P(3)-R in a manner that does not disrupt the S1P(3)-R-S1P binding. The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the molecular basis of the receptor function, and provides the bases for further rational design of more potent and drug-like S1P(3)-R allosteric agonists. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.075

文献信息

• Carboxamides
  申请人：BASF Aktiengesellschaft

  公开号：US05201932A1

  公开（公告）日：1993-04-13

  Carboxamides Ia, Ib, Ic and Id ##STR1## (X=O, S; R.sup.1 =H, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted benzyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy or phenylthio, a substituted or unsubstituted 5- or 6-membered heterocyclic radical containing one or two heteroatoms, cycloalkyl-substituted alkyl, substituted or unsubstituted alkenyl which may be epoxidized, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl or cycloalkenyl; R.sup.1 '=cycloalkyl-substituted alkyl, substituted or unsubstituted alkenyl which may be epoxidized, substituted or unsubstituted cycloalkenyl; R.sup.2 =CHO, 4,5-dihydrooxazol-2-yl, COYR.sup.5, CONR.sup.6 R.sup.7 ; Y=O, S; R.sup.5 =H, substituted or unsubstituted alkyl, cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted phenyl, a 5- or 6-membered heterocyclic radical containing up to 3 heteroatoms, benzotriazole, N-phthalimido, tetrahydrophthalimido, succinimido, maleiimido, 2,2-dimethyl-1,3-dioxolan-4-ylmethyl, 1,3-dioxolan-2-on-4-ylmethyl, and when Y.dbd.O: one equivalent of a cation from the group of the alkali or alkaline earth metals, Mn, Cu, Fe ammonium and substituted ammonium, a radical --N.dbd.CR.sup.8 R.sup.9 or --W--Z; R.sup.8, R.sup.9 .dbd.H, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, cycloalkyl, alkoxy, furanyl, substituted or unsubstituted phenyl; R.sup.8 +R.sup.9 =4-7-membered methylene chain; W=alkylene chain, ethoxyethylene chain, butylene, butynylene chain; Z=a molecular moiety bonded to W in the .omega.-position and is the same as that linked to W in the .alpha.-position of W; R.sup.6 .dbd.H, alkyl, cycloalkyl; R.sup.7 .dbd.H; alkyl; --C(O-alkyl).dbd.N--H or --(O--alkyl).dbd.N--alkyl; R.sup.6 +R.sup.7 =4-5-membered methylene chain; R.sup.3 .dbd.H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl; R.sup.4 .dbd.H, OH, alkoxy, subsituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, di-(C.sub.1 -C.sub.4)-alkylamino, a substituted or unsubstituted 5- or 6-membered heterocyclic radical containing one or two heteroatoms, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl; R.sub.3 +R.sub.4 =4-7-membered methylene chain which may be interrupted by O, S or N--CH.sub.3, or --(CH.sub.2).sub.3 --CO--) and their environmentally tolerated salts. The compounds Ia to Id are suitable as herbicides.

  Carboxamides Ia，Ib，Ic和Id ##STR1## （其中X = O，S; R1 = H，卤素，取代或未取代的烷基，取代或未取代的苯甲基，烷氧基，烷硫基，卤代烷氧基，卤代烷硫基，取代或未取代的苯基，取代或未取代的苯氧基或苯硫基，含有一个或两个杂原子的取代或未取代的5-或6-成员杂环基，环烷基取代的烷基，取代或未取代的烯基（可能为环氧化的），取代或未取代的炔基，取代或未取代的环烷基或环烯基; R1 '= 环烷基取代的烷基，取代或未取代的烯基（可能为环氧化的），取代或未取代的环烯基; R2 = CHO，4,5-二氢噁唑-2-基，COYR5，CONR6R7; Y = O，S; R5 = H，取代或未取代的烷基，环烷基，取代或未取代的烯基，取代或未取代的环烯基，取代或未取代的炔基，取代或未取代的苯基，含有最多3个杂原子的5-或6-成员杂环基，苯三唑，N-邻苯二甲酰亚胺，四氢邻苯二甲酰亚胺，琥珀酰亚胺，马来酰亚胺，2,2-二甲基-1,3-二氧环戊烷-4-基甲基，1,3-二氧环戊烷-2-酮-4-基甲基，当Y = O时：来自碱金属或碱土金属，锰，铜，铁，铵和取代铵的阳离子中的一个当Y = O时：一个基团--N = CR8R9或--W--Z; R8，R9 = H，取代或未取代的烷基，取代或未取代的卤代烷基，环烷基，烷氧基，呋喃基，取代或未取代的苯基; R8 + R9 = 4-7成员的亚甲基链; W = 烷基链，乙氧基乙烯基链，丁基，丁炔基链; Z = 与W在.omega.-位置连接的分子基团，与W在.α.-位置连接的相同; R6 = H，烷基，环烷基; R7 = H; 烷基; --C（O-烷基）= N--H或--（O-烷基）= N-烷基; R6 + R7 = 4-5成员的亚甲基链; R3 = H，取代或未取代的烷基，取代或未取代的环烷基; R4 = H，OH，烷氧基，取代或未取代的烷基，取代或未取代的环烷基，取代或未取代的烯基，取代或未取代的炔基，二（C1-C4）-烷基氨基，含有一个或两个杂原子的取代或未取代的5-或6-成员杂环基，取代或未取代的苯基，取代或未取代的萘基; R3 + R4 = 4-7成员的亚甲基链，可以被O，S或N-CH3中断，或--（CH2）3--CO--）及其环境耐受盐。化合物Ia到Id适用于除草剂。
• US5201932A
  申请人：——

  公开号：US5201932A

  公开（公告）日：1993-04-13
• Discovery, design and synthesis of a selective S1P3 receptor allosteric agonist
  作者：Miguel Guerrero、Ramulu Poddutoori、Mariangela Urbano、Xuemei Peng、Timothy P. Spicer、Peter S. Chase、Peter S. Hodder、Marie-Therese Schaeffer、Steven Brown、Hugh Rosen、Edward Roberts

  DOI：10.1016/j.bmcl.2013.09.075

  日期：2013.12

  Potent and selective S1P(3) receptor (S1P(3)-R) agonists may represent important proof-of-principle tools used to clarify the receptor biological function and assess the therapeutic potential of the S1P(3)-R in cardiovascular, inflammatory and pulmonary diseases. N, N-Dicyclohexyl-5-propylisoxazole-3-carboxamide was identified by a high-throughput screening of MLSMR library as a promising S1P(3)-R agonist. Rational chemical modifications of the hit allowed the identification of N, N-dicyclohexyl-5-cyclopropylisoxazole-3-carboxamide, a S1P(3)-R agonist endowed with submicromolar activity and exquisite selectivity over the remaining S1P(1,2,4,5)-R family members. A combination of ligand competition, site-directed mutagenesis and molecular modeling studies showed that the N, N-dicyclohexyl-5-cyclopropylisoxazole-3-carboxamide is an allosteric agonist and binds to the S1P(3)-R in a manner that does not disrupt the S1P(3)-R-S1P binding. The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the molecular basis of the receptor function, and provides the bases for further rational design of more potent and drug-like S1P(3)-R allosteric agonists. (C) 2013 Elsevier Ltd. All rights reserved.