((3-amino-phenyl)-tert-butoxycarbonyl-amino)-acetic acid methyl ester | 528883-12-7

• 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: ((3-amino-phenyl)-tert-butoxycarbonyl-amino)-acetic acid methyl ester
• 英文别名: methyl 2-[3-amino-N-[(2-methylpropan-2-yl)oxycarbonyl]anilino]acetate
• CAS: 528883-12-7
• 化学式: C₁₄H₂₀N₂O₄
• 分子量: 280.324
• InChiKey: CRFAXRLBOSZNPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ((3-amino-phenyl)-tert-butoxycarbonyl-amino)-acetic acid methyl ester 在 4-二甲氨基吡啶 、 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 (tert-butoxycarbonyl-(3-(2-(5-cyclohexyl-1-(3,3-dimethyl-2-oxo-butyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-acetylamino)-phenyl)-amino)-acetic acid
  参考文献：
  名称：

  Optimization of 1,3,4-Benzotriazepine-Based CCK₂ Antagonists to Obtain Potent, Orally Active Inhibitors of Gastrin-Mediated Gastric Acid Secretion

  摘要：

  Starting from a novel, achiral 1,3,4-benzotriazepine-based CCK2 receptor antagonist, a process of optimization has afforded further compounds of this type that maintain the nanomolar affinity for recombinant, human CCK2 receptors and high selectivity over CCK1 receptors observed in the initial lead but display more potent inhibition of pentagastrin-stimulated gastric acid secretion in vivo. Moreover, this has largely been achieved without altering their potency at wild-type canine and rat receptors, as judged by their displacement of [I-125]-BH-CCK-8S in a radioligand binding assay and by their activity in an isolated, perfused rat stomach bioassay, respectively. 2-(5-Cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-N-(3-(5-oxo-2,5-dihydro- [1,2,4]oxadiazol-3-yl)-phenyl)-acetamide (47) was identified as the most effective compound stemming from this approach, proving to be a potent inhibitor of pentagastrin-stimulated gastric acid secretion in rats and dogs by intravenous bolus as well as by enteral administration.

  DOI：

  10.1021/jm070139l
• 作为产物：
  描述：

  3-硝基苯异氢酸酯 生成 ((3-amino-phenyl)-tert-butoxycarbonyl-amino)-acetic acid methyl ester
  参考文献：
  名称：

  [EN] 1, 3, 4-BENZOTRIAZEPIN-2-ONE SALTS AND THEIR USE AS CCK RECEPTOR LIGANDS
  [FR] SELS DE 1,3,4-BENZOTRIAZEPINE ET LEUR UTILISATION COMME LIGANDS DU RECEPTEUR DE CCK

  摘要：

  该发明涉及公式（I）化合物的药用可接受盐，其中：W为N或N+-O-；R2为可选择取代的C1至C18烃基团，其中最多三个C原子可选择地被N、O和/或S原子取代。R3为-(CR11R12)m-X-(CR13R14)p-R9；m为0、1、2、3或4；p为0、1或2；X为键、-CR15=CR16-、-C≡C-、C(O)NH、NHC(O)、C(O)NMe、NMeC(O)、C(O)O、NHC(O)NH、NHC(O)O、OC(O)NH、NH、O、CO、SO2、SO2NH、C(O)NHNH；R9为H、C1至C6烷基或苯基、萘基、吡啶基、苯并咪唑基、吲哚基、喹啉基、异喹啉基、四氢异喹啉基、吲哚啉基、异吲哚啉基、吲哚基、异吲哚基或2-吡啶酰基，取代为-L-Q。R4为可选择取代的C1至C18烃基团，其中最多三个C原子可选择地被N、O和/或S原子取代；这些盐可用于治疗胃泌素相关疾病。

  公开号：

  WO2004101533A1

文献信息

• [EN] GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS<br/>[FR] LIGANDS DES RECEPTEURS DE LA GASTRINE ET DE LA CHOLECYSTOKININE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2000027823A1

  公开（公告）日：2000-05-18

  Compounds of formula (I) and their pharmaceutically acceptable salts are ligands at gastrin and/or cholecystokinin receptors. X and Y are independently =N-, -N(R5)- =CH-, -S- or -O-. n is from 1 to 4; R1 is H or C¿1? to C15 hydrocarbyl R?2¿ is selected from H, Me, Et, Pr and OH, R¿3? is selected from H, Me, Et and Pr; or (when n is greater than 1) each R?3¿ is independently selected from H, Me, Et and Pr, or two R3 groups on neighbouring carbon atoms are linked to form a C¿3? to C6 carbocylic ring, or R?2 and R3¿ on the same carbon atom together represent an =O group; R4 is C1 to C15 hydrocarbyl Z is -(NR7)a-CO-(NR8)b- (wherein a is 0 or 1, b is 0 or 1, -CO-NR7-CH2-CO-NR8-, -CO-O-, -CH¿2?-CH2-, -CH=CH-, -CH2-NR?8¿- or a bond; Q is -R9V, or (II), (wherein R9 is -CH¿2?-; -CH2-CH2-; or (III), R?9 and R8¿, together with the nitrogen atom to which R8 is attached, form a piperidine or pyrrolidine ring which is substituted by V; V is -CO-NH-SO¿2?-Ph, -SO2-NH-CO-Ph, -CH2OH, or a group of the formula -R?10¿U, (wherein U is -COOH, tetrazolyl, -CONHOH- or -SO¿3?H; and R?10¿ is a bond; C¿1? to C6 hydrocarbylene, -O-(C1 to C3 alkylene)-; -SO2NR?11-CHR12¿-; -CO-NR?11-CHR12¿-, or -NH-(CO)¿c?-CH2-, c being 0 or 1).

  式(I)化合物及其药学上可接受的盐是胃泌素和/或胆囊收缩素受体的配体。X和Y独立地为=N-，-N（R5）-，=CH-，-S-或-O-。n为1至4；R1为H或C1至C15的烃基；R2从H，Me，Et，Pr和OH中选择，R3从H，Me，Et和Pr中选择；或（当n大于1时）每个R3独立地从H，Me，Et和Pr中选择，或相邻碳原子上的两个R3基团连接形成C3至C6的环烷基，或R2和R3在同一碳原子上共同表示一个=O基团；R4为C1至C15的烃基，Z为-(NR7)a-CO-(NR8)b-（其中a为0或1，b为0或1，-CO-NR7-CH2-CO-NR8-，-CO-O-，- - -，-CH=CH-，- -NR8-或键；Q为-R9V，或（II），（其中R9为- -；- - -；或（III），R9和R8，连同R8所连接的氮原子，形成被V取代的哌嗪或吡咯烷环；V为-CO-NH-SO2-Ph，-SO2-NH-CO-Ph，- OH，或式-R10U的基团（其中U为-COOH，四唑基，-CONHOH-或-SO3H；R10为键；C1至C6的烃亚基，-O-（C1至C3的烷基）-；-SO2NR11-CHR12-；-CO-NR11-CHR12-，或-NH-（CO）c- -，其中c为0或1）。
• [EN] BENZOTRIAZEPINES AS GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS<br/>[FR] BENZOTRIAZEPINES UTILISEES COMME LIGANDS DE RECEPTEURS DE CHOLECYSTOQUININE ET DE GASTRINE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2003041714A1

  公开（公告）日：2003-05-22

  This invention relates to a compound of formula (I) wherein: W is N or N+-O-; and R1 to R5 are as defined in the description, for use for the treatment of gastrin related disorders.

  本发明涉及式(I)的化合物，其中：W为N或N+-O-; R1至R5如描述中所定义，用于治疗胃泌素相关疾病。
• Benzotriazepnes as gastrin and cholecystokinin receptor ligands
  申请人：McDonald Mair Iain

  公开号：US20060003993A1

  公开（公告）日：2006-01-05

  This invention relates to a compound of formula (I) wherein: W is N or N + —O − ; and R 1 to R 5 are as defined in the description, for use for the treatment of gastrin related disorders.

  本发明涉及一种化合物，其化学式为(I)，其中：W为N或N+—O−；R1至R5如描述中定义的那样，用于治疗胃泌素相关疾病。
• Benzotriazapinone salts and methods for using same
  申请人：Abdel-Magid F. Ahmed

  公开号：US20050026911A1

  公开（公告）日：2005-02-03

  This invention relates to pharmaceutically acceptable salts of compounds of formula (I) wherein: W is N or N + —O − ; R 1 and R 5 are independently H, C 1 to C 6 alkyl, (C 1 to C 6 alkyl)oxy, thio, (C 1 to C 6 alkyl)thio, carboxy, carboxy(C 1 to C 6 alkyl), formyl, (C 1 to C 6 alkyl)carbonyl, (C 1 to C 6 alkyl)oxycarbonyl, (C 1 to C 6 alkyl)carbonyloxy, nitro, trihalomethyl, hydroxy, hydroxy(C 1 to C 6 alkyl), amino, (C 1 to C 6 alkyl)amino, di(C 1 to C 6 alkyl)amino, aminocarbonyl, halo, halo(C 1 to C 6 alkyl), aminosulfonyl, (C 1 to C 6 alkyl)sulfonylamino, (C 1 to C 6 alkyl)aminocarbonyl, di(C 1 to C 6 alkyl)aminocarbonyl, [N-Z](C 1 to C 6 alkyl)carbonylamino, formyloxy, formamido, (C 1 to C 6 alkyl)aminosulfonyl, di(C 1 to C 6 alkyl)aminosulfonyl, [N-Z](C 1 to C 6 alkyl)sulfonylamino or cyano; or R 1 and R 5 together form a methylenedioxy group; R 2 is an optionally substituted C 1 to C 18 hydrocarbyl group wherein up to three C atoms may optionally be replaced by N, O and/or S atoms. R 3 is —(CR 11 R 12 ) n —X_(CR 13 R 14 )—R 9 ; m is 0, 1, 2, 3 or 4; p is 0, 1 or 2; X is a bond, —CR 15 ═CR 16 —, —C≡C—, C(O)NH, NHC(O), C(O)NMe, NMeC(O), C(O)O, NHC(O)NH, NHC(O)O, OC(O)NH, NH, O, CO, SO 2 , SO 2 NH, C(O)NHNH, R 9 is H; C 1 to C 6 alkyl; or phenyl, naphthyl, pyridyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, indolinyl, isoindolinyl, indolyl or isoindolyl all optionally substituted with 1, 2 or 3 groups independently selected from -L-Q wherein: L is a bond, or a group of the formula —(CR 17 R 18 ) v —Y—(CR 17 R 18 ) w , wherein v and w are independently 0, 1, 2 or 3, and Y is a bond, —CR 15 ═CR 16 —, phenyl, furanyl, thiophenyl, pyrrolyl, thiazolyl, imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, isoxazolonyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, pyridyl or pyridazyl; and Q is H, (C 1 to C 6 alkyl)oxy, [N-Z](C 1 to C 6 alkyl)oxy(C 1 to C 6 alkyl)amino, thio, (C 1 to C 6 alkyl)thio, carboxy(C 1 to C 6 alkyl)thio, carboxy, carboxy(C 1 to C 6 alkyl), carboxy(C 1 to C 6 alkenyl), [N-Z]carboxy(C 1 to C 6 alkyl)amino, carboxy(C 1 to C 6 alkyl)oxy, formyl, (C 1 to C 6 alkyl)carbonyl, (C 1 to C 6 alkyl)oxycarbonyl, (C 1 to C 6 alkyl)carbonyloxy, nitro, trihalomethyl, hydroxy, amino, [N-Z](C 1 to C 6 alkyl)amino, aminocarbonyl, (C 1 to C 6 alkyl)aminocarbonyl, di(C 1 to C 6 alkyl)aminocarbonyl, [N-Z] (C 1 to C 6 alkyl)carbonylamino, C 5 to C 8 cycloalkyl, [N-Z](C 1 to C 6 alkyl)carbonyl(C 1 to C 6 alkyl)amino, halo, halo(C 1 to C 6 alkyl), sulfamoyl, [N-Z](C 1 to C 6 alkyl)sulfonylamino, (C 1 to C 6 alkyl)sulfonylaminocarbonyl, carboxy(C 1 to C 6 alkyl)sulfonyl, carboxy(C 1 to C 6 alkyl)sulfinyl, tetrazolyl, [N-Z]tetrazolylamino, cyano, amidino, amidinothio, SO 3 H, formyloxy, formamido, C 3 to C 8 cycloalkyl, (C 1 to C 6 alkyl)sulphamoyl, di(C 1 to C 6 alkyl)sulphamoyl, (C 1 to C 6 alkyl)carbonylaminosulfonyl, 5-oxo-2,5-dihydro[1,2,4]oxadiazolyl, carboxy(C 1 to C 6 alkyl)carbonylamino, tetrazolyl(C 1 to C 6 alkyl)thio, [N-Z]tetrazolyl(C 1 to C 6 alkyl)amino, 5-oxo-2,5-dihydro[1,2,4]thiadiazolyl, 5-oxo-1,2-dihydro[1,2,4]triazolyl, [N-Z](C 1 to C 6 alkyl)amino(C 1 to C 6 alkyl)amino, or a group of the formula wherein P is O, S or NR 19 ; Z is H, C 1 to C 6 alkyl, t-butoxycarbonyl, acetyl, benzoyl or benzyl; R 4 is an optionally substituted C 1 to C 18 hydrocarbyl group wherein up to three C atoms may nally be replaced by N, O and/or S atoms; and R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 19 are independently H or C 1 to C 3 alkyl. Such salts are useful, for example, for the treatment of gastrin related disorders.

  本发明涉及公式（I）化合物的药学上可接受的盐，其中：W是N或N+—O−；R1和R5独立地是H、C1到C6烷基、（C1到C6烷基）氧、硫、（C1到C6烷基）硫、羧基、羧基（C1到C6烷基）、甲酰基、（C1到C6烷基）羰基、（C1到C6烷基）氧羰基、（C1到C6烷基）羰氧基、硝基、三卤甲基、羟基、羟基（C1到C6烷基）、氨基、（C1到C6烷基）氨基、二（C1到C6烷基）氨基、氨基羰基、卤、卤（C1到C6烷基）、氨基磺酰基、（C1到C6烷基）磺酰氨基、（C1到C6烷基）氨基羰基、二（C1到C6烷基）氨基羰基、[N-Z]（C1到C6烷基）羰基氨基、甲酰氧基、甲酰胺基、（C1到C6烷基）氨基磺酰基、二（C1到C6烷基）氨基磺酰基、[N-Z]（C1到C6烷基）磺酰氨基或氰基；或者R1和R5一起形成一个亚甲二氧基基团；R2是一个可选择取代的C1到C18烃基，其中最多三个C原子可以用N、O和/或S原子替换。R3是-（CR11R12）n-X_(CR13R14）-R9；m为0、1、2、3或4；p为0、1或2；X是一个键，-CR15═CR16-，-C≡C-，C（O）NH，NHC（O），C（O）NMe，NMeC（O），C（O）O，NHC（O）NH，NHC（O）O，OC（O）NH，NH，O，CO，SO2，SO2NH，C（O）NHNH，R9是H、C1到C6烷基或苯基、萘基、吡啶基、苯并咪唑基、吲哚基、喹啉基、异喹啉基、吲哚啉基或异吲哚啉基，所有这些基团都可以选择性地用1、2或3个独立选择的-L-Q取代，其中：L是一个键，或者是公式-（CR17R18）v-Y-（CR17R18）w的基团，其中v和w独立地为0、1、2或3，Y是一个键，-CR15═CR16-，苯基、呋喃基、噻吩基、吡咯基、噻唑基、咪唑基、氧咪唑基、异噁唑基、吡唑基、异噁唑基、哌嗪基、哌啶基、吗啉基、吡咯烷基、异噻唑基、三唑基、噻二唑基、吡啶基或吡嗪基；Q是H、（C1到C6烷基）氧、[N-Z]（C1到C6烷基）氧（C1到C6烷基）氨基、硫、（C1到C6烷基）硫、羧基（C1到C6烷基）硫、羧基、羧基（C1到C6烯基）、[N-Z]羧基（C1到C6烷基）氨基、羧基（C1到C6烷基）氧、甲酰基、（C1到C6烷基）羰基、（C1到C6烷基）氧羰基、（C1到C6烷基）羰氧基、硝基、三卤甲基、羟基、氨基、[N-Z]（C1到C6烷基）氨基、氨基羰基、（C1到C6烷基）氨基羰基、二（C1到C6烷基）氨基羰基、[N-Z]（C1到C6烷基）羰基氨基、C5到C8环烷基、[N-Z]（C1到C6烷基）羰基（C1到C6烷基）氨基、卤、卤（C1到C6烷基）、磺酰氨基、[N-Z]（C1到C6烷基）磺酰氨基、（C1到C6烷基）磺酰氨基羰基、羧基（C1到C6烷基）磺酰基、羧基（C1到C6烷基）亚磺酰基、四唑基、[N-Z]四唑基氨基、氰基、氨基甲酰基、氨基甲硫基、SO3H、甲酰氧基、甲酰胺基、C3到C8环烷基、（C1到C6烷基）磺酰氨基、二（C1到C6烷基）磺酰氨基、（C1到C6烷基）羰基氨基磺酰基、5-氧代-2,5-二氢[1,2,4]噁唑基、羧基（C1到C6烷基）羰基氨基、四唑基（C1到C6烷基）硫、[N-Z]四唑基（C1到C6烷基）氨基、5-氧代-2,5-二氢[1,2,4]噻唑基、5-氧代-1,2-二氢[1,2,4]三唑基、[N-Z]（C1到C6烷基）氨基（C1到C6烷基）氨基，或者是公式的基团：其中P是O、S或NR19；Z是H、C1到C6烷基、t-丁氧羰基、乙酰基、苯甲酰基或苄基；R4是一个可选择取代的C1到C18烃基，其中最多三个C原子可以用N、O和/或S原子替换；R11、R12、R13、R14、R15、R16、R17、R18和R19独立地是H或C1到C3烷基。这种盐可用于治疗胃泌素相关疾病等。
• 2-Aminooxazolines as TAAR1 ligands
  申请人：Galley Guido

  公开号：US20080261920A1

  公开（公告）日：2008-10-23

  The invention relates to compounds of formula I wherein X, Y, R 1 , R 2 , and n are as defined herein or to a pharmaceutically suitable acid addition salt thereof. The invention also relates to pharmaceutical compositions containing such compounds and methods for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases include depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及化合物I的公式，其中X，Y，R1，R2和n如本文所定义，或其药学上适宜的酸加盐。本发明还涉及含有这种化合物的制药组合物和治疗与微量胺相关受体的生物学功能相关的疾病的方法，这些疾病包括抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍、压力相关障碍、精神障碍、精神分裂症、神经系统疾病、帕金森病、神经退行性疾病、阿尔茨海默病、癫痫、偏头痛、物质滥用和代谢性疾病、进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍和功能障碍、睡眠和昼夜节律障碍以及心血管疾病。