N-[3-(二甲氨基)丙基]硫脲 | 196809-80-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫脲类
• 中文名称: N-[3-(二甲氨基)丙基]硫脲
• 英文名称: N-[3-(dimethylamino)propyl]thiourea
• 英文别名: dimaprit；3-(dimethylamino)propylthiourea
• CAS: 196809-80-0
• 化学式: C₆H₁₅N₃S
• mdl: MFCD00041196
• 分子量: 161.271
• InChiKey: QCGUXRFTJDHKTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  73.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[3-(二甲氨基)丙基]硫脲 在 lithium aluminium tetrahydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 77.0h， 生成 2(S)-<(2-benzoylphenyl)amino>-3-<4-<2-<2-<<3-(dimethylamino)propyl>amino>-5-methylthiazol-4-yl>ethoxy>phenyl>propionic acid methyl ester
  参考文献：
  名称：

  N-(2-Benzoylphenyl)-l-tyrosine PPARγ Agonists. 2. Structure−Activity Relationship and Optimization of the Phenyl Alkyl Ether Moiety

  摘要：

  We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propanoic (2) (PPAR gamma pK(i) = 8.94, PPAR gamma, pEC(50) = 9.47) as a potent and selective PPAR gamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPAR gamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-pyridin-4-yloxazol-4-yl)ethoxy]phenyl}propionic acid (16) (PPAR gamma pK(i) = 8.85, PPAR gamma pEC(50) = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-{2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}pheynyl)propionic acid (24) (PPAR gamma pK(i) = 8.6, PPAR gamma pEC(50) = 8.89) provided two potent and selective PPAR gamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPAR gamma ligands (PPAR gamma pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPAR gamma binding, functional activity, selectivity, and aqueous solubility.

  DOI：

  10.1021/jm980413z

文献信息

• Rapid assembly of 2-aminoimidazolones on solid support
  作者：Kexin Yang、Boliang Lou、Hossain Saneii

  DOI：10.1016/s0040-4039(02)00828-6

  日期：2002.6

  straightforward solid-phase synthesis of 2-aminoimidazolone derivatives is described. The synthesis starts with immobilization of thioureas onto solid support, followed by HBTU/DIEA assisted coupling of Boc-protected amino acids. Upon removal of the Boc group, intramolecular cyclization and simultaneous cleavage are promoted by polyamine resin to give the 2-aminoimidazolone derivatives in good yields and excellent

  描述了2-氨基咪唑酮衍生物的直接固相合成。合成开始于将硫脲固定在固体支持物上，然后由HBTU / DIEA辅助Boc保护的氨基酸偶联。除去Boc基团后，聚胺树脂促进了分子内环化和同时裂解，从而以良好的收率和优异的纯度得到了2-氨基咪唑啉酮衍生物。
• [EN] N, N', N''-TRIS-(3-DIMETHYLAMINOPROPYL)-GUANIDINE. THE PROCEDURE OF PREPARATION FROM CARBODIIMIDE AND APPLICATION IN REACTIONS OF TRANSESTERIFICATION OF OIL<br/>[FR] N, N', N''-TRIS-(3-DIMETHYLAMINOPROPYL)-GUANIDINE. PROCEDE DE PREPARATION ET APPLICATION DANS LA TRANSESTERIFICATION D'HUILES VEGETALES
  申请人：RUDER BOSKOVIC INST

  公开号：WO2005100306A1

  公开（公告）日：2005-10-27

  The present invention provides procedures for preparation of N, N', N''-tris-(3-dimethylaminopropyl)-guanidine by addition of 3-dimethylaminopropylamine to N1, N3-bis-(3-dimethylaminopropyl)-carbodiimide. The latter compound was prepared in two steps starting from commercially available 3-dimethylaminpropyl amine and carbon disulfide followed by desulfurization of the formed thiourea with yellow mercury(II)-oxide. The so obtained guanidine derivative was successfully applied as catalyst in the transesterification of sunflower, soybean and rapeseed oil.

  本发明提供了一种通过将3-二甲基氨基丙胺加入N1, N3-双(3-二甲基氨基丙基)-碳酰亚胺制备N, N', N''-三-(3-二甲基氨基丙基)-胍的方法。后一种化合物是通过从商业可获得的3-二甲基氨基丙胺和二硫化碳开始的两步法制备的，随后用二氧化汞(II)对生成的硫氨基脲进行脱硫。所得的胍衍生物成功地应用于向日葵、大豆和油菜籽油的酯交换反应中作为催化剂。
• [EN] SUBSTITUTED 4-HYDROXY-PHENYLALCANOIC ACID DERIVATIVES WITH AGONIST ACTIVITY TO PPAR-GAMMA<br/>[FR] DERIVES D'ACIDE 4-HYDROXY-PHENYLALCANOIQUE SUBSTITUE POSSEDANT UNE ACTIVITE AGONISTE ENVERS PPAR-GAMMA
  申请人：GLAXO GROUP LIMITED

  公开号：WO1997031907A1

  公开（公告）日：1997-09-04

  (EN) A compound having formula (I), wherein A is selected from the group consisting of: (i) phenyl, wherein said phenyl is optionally substituted by one or more halogen atoms, C1-6alkyl, C1-3alkoxy, C1-3fluoroalkoxy, nitrile, or -NR7R8 where R7 and R8 are independently hydrogen or C1-3alkyl; (ii) a 5- or 6-membered heterocyclic group containing at least one heteroatom selected from oxygen, nitrogen and sulfur; and (iii) a fused bicyclic ring (a), wherein ring C represents a heterocyclic group as defined in point (ii) above, which bicyclic ring is attached to group B via a ring atom of ring C; B is selected from the group consisting of: (iv) C1-6alkylene; (v) -MC1-6alkylene or C1-6alkyleneMC1-6alkylene, wherein M is O, S, or -NR2 wherein R2 represents hydrogen or C1-3 alkyl; (vi) a 5- or 6-membered heterocyclic group containing at least one nitrogen heteroatom and optionally at least one further heteroatom selected from oxygen, nitrogen and sulfur and optionally substituted by C1-3 alkyl; and (vii) Het-C1-6alkylene, wherein Het represents a heterocyclic group as defined in point (vi) above; Alk represents C1-3alkylene; R1 represents hydrogen or C1-3alkyl; Z is selected from the group consisting of: (viii) -(C1-3alkylene) phenyl, which phenyl is optionally substituted by one or more halogen atoms; and (ix) -NR3R4, wherein R3 represents hydrogen or C1-3alkyl, and R4 represents -Y-(C=O)-T-R5, or -Y-(CH(OH))-T-R5.(FR) Cette invention concerne un composé correspondant à la formule (I) où A est choisi dans le groupe comprenant les éléments suivants: (i) un phényle éventuellement substitué par un ou plusieurs atomes halogènes, alkyle C1-6, alcoxy C1-3, fluoroalcoxy C1-3, nitrile ou -NR7R8, R7 et R8 représentant indépendamment hydrogène ou alkyle C1-3; (ii) un groupe hétérocyclique à 5 ou 6 branches contenant un ou plusieurs hétéroatomes choisis parmi oxygène, azote et soufre; et (iii) un anneau (a) bicyclique fusionné dans lequel l'anneau C représente un groupe hétérocyclique tel que défini dans le point (ii) susmentionné, cet anneau bicyclique étant attaché au groupe B par un des atomes de l'anneau C. B est choisi dans le groupe comprenant les éléments suivants: (iv) alcylène C1-6; (v) -MC1-6alcylène ou C1-6alcylèneMC1-6alcylène où M représente O, S ou NR2, R2 représentant hydrogène ou alkyle C1-3; (vi) un groupe hétérocyclique à 5 ou 6 branches contenant au moins un hétéroatome d'azote et, éventuellement, un ou plusieurs autres hétéroatomes choisis parmi oxygène, azote et soufre, ledit groupe étant éventuellement substitué par alkyle C1-3; et (vii) Het-C1-6alcylène où Het représente un groupe hétérocyclique tel que défini dans le point (vi) susmentionné. Alk représente alcylène C1-3, tandis que R1 représente hydrogène ou alkyle C1-3, et que Z est choisi dans le groupe comprenant les éléments suivants: (viii) -(C1-3alcylène)phényle, lequel phényle est éventuellement substitué par un ou plusieurs atomes halogènes; et enfin (ix) -NR3R4 où R3 représente hydrogène ou alkyle C1-3, et R4 représente -Y-(C=O)-T-R5 ou -Y-(CH(OH))-T-R5.

  化合物的化学式为(I)，其中A选自以下组中的一种：(i)苯基，其中所述苯基可以选用一个或多个卤素原子，C1-6烷基，C1-3烷氧基，C1-3氟烷氧基，腈或-NR7R8，其中R7和R8独立地表示氢或C1-3烷基；(ii)含有至少一个氧、氮或硫杂原子的5-或6-成员杂环基；以及(iii)融合的双环环(a)，其中环C代表上述(ii)中定义的杂环基，该双环环通过环C的一个环原子连接到基团B上；B选自以下组中的一种：(iv)C1-6烷基；(v)-MC1-6烷基或C1-6烷基MC1-6烷基，其中M为O、S或-NR2，而R2表示氢或C1-3烷基；(vi)含有至少一个氮杂原子的5-或6-成员杂环基，且可选地含有至少一个来自氧、氮或硫的进一步杂原子，并可选地被C1-3烷基取代；以及(vii)Het-C1-6烷基，其中Het代表上述(vi)中定义的杂环基；Alk表示C1-3烷基；R1表示氢或C1-3烷基；Z选自以下组中的一种：(viii) -(C1-3烷基)苯基，所述苯基可以选用一个或多个卤素原子；以及(ix) -NR3R4，其中R3表示氢或C1-3烷基，而R4表示-Y-(C=O)-T-R5或-Y-(CH(OH))-T-R5。
• N-terminal sequencing of proteins and peptides
  申请人：City of Hope

  公开号：US05432091A1

  公开（公告）日：1995-07-11

  An improved method for the N-terminal sequential degradation of proteins and peptides is disclosed. The protein or peptide to be sequenced is reacted with a compound effective to impart a tertiary amine functionality to the thiazolinone derivative of a cleaved terminal amino acid of the peptide.

  本发明揭示了一种改进的蛋白质和肽N末端序列降解方法。待测蛋白质或肽与一种有效的化合物反应，以使肽的剪切末端氨基酸的噻唑酮衍生物具有三级胺官能团。
• Broadspectrum heterocyclic substituted phenyl containing sulfonamide hiv protease inhibitors
  申请人：Coulton Steven

  公开号：US20050222215A1

  公开（公告）日：2005-10-06

  The present invention concerns the compounds having the formula (I), N-oxides, salt, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein Haryl is an aromatic monocyclic, bicyclic or tricyclic heterocycle having 3 to 14 ring members which contains one or more heteroatom ring members selected from nitrogen, oxygen and sulfur and which may optionally be substituted on (i) one or more carbon atoms by C 1-6 alkyl, halogen, hydroxy, optionally mono- or disubstituted amino, nitro, cyano, haloC 1-6 alkyl, carboxyl, C 3-7 cycloalkyl, optionally mono- or disubstituted aminocarbonyl, methylthio, methylsulfonyl, aryl, (R 7a ) n -M-R 7b , Het 1 and Het 2 ; whereby the optional substituents on any amino function are independently selected from R 5 and -A-R 6 ; and on (ii) a nitrogen atom if present by hydroxy or -A-R 6 . It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.

  本发明涉及具有式(I)的化合物，N-氧化物，盐，立体异构体形式，外消旋混合物，前药，酯和代谢物，其中Haryl是具有3至14个环成员的芳香单环，双环或三环杂环，其中包含从氮，氧和硫中选择的一个或多个杂原子环成员，并且可以在（i）一个或多个碳原子上由C1-6烷基，卤素，羟基，可选的单取代或双取代氨基，硝基，氰基，卤代C1-6烷基，羧基，C3-7环烷基，可选的单取代或双取代氨基甲酰基，甲硫基，甲基磺酰基，芳基，（R7a）n-M-R7b，Het1和Het2取代，其中任何氨基功能上的可选取代基均独立地选择自R5和-A-R6; 并且在（ii）氮原子存在时由羟基或-A-R6取代。它进一步涉及它们作为广谱HIV蛋白酶抑制剂的用途，以及它们的制备方法，以及包含它们的制药组合物和诊断试剂盒。它还涉及与另一种抗逆转录病毒药物的组合，以及它们作为参考化合物或试剂在检测中的使用。