[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]acetic acid | 957471-86-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: [1-(4-methoxybenzyl)-1H-tetrazol-5-yl]acetic acid
• 英文别名: 2-[1-[(4-Methoxyphenyl)methyl]tetrazol-5-yl]acetic acid
• CAS: 957471-86-2
• 化学式: C₁₁H₁₂N₄O₃
• 分子量: 248.241
• InChiKey: WSWKREPVKGYTRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [1-(4-methoxybenzyl)-1H-tetrazol-5-yl]acetic acid 在 草酰氯 作用下， 生成 2-(5-(4-methoxybenzyl)tetrazolyl)acetyl chloride
  参考文献：
  名称：

  N-Terminal carboxyl and tetrazole-containing amides as adjuvants to Grb2 SH2 domain ligand binding

  摘要：

  High affinity binding of peptides to Src homology 2 (SH2) domains, often requires the presence of phosphotyrosyl (pTyr) or pTyr-mimicking moieties in the N-terminal position of the binding ligand. Several reports have shown that N-alpha-acylation of the critical pTyr residue can result in increased SH2 domain binding potency. For Grb2 SH2 domains which recognize pTyr-Xxx-Asn-NH2 motifs, significant potency enhancement can be incurred by N-alpha-(3-amino)Z derivatization of tripeptides such as pTyr-Xxe-Asn-NH2. Using ligands based on the high affinity pY-Ac(6)c-Asn-(naphthylpropylamide) motif, (where Ac(6)c = 1-aminocyclohex-anecarboxylic acid), additional reports have shown moderate potentiating effects of N-alpha-oxalyl derivatization. The current study examined variations of the N-alpha-oxalyl theme in the context of a Xxx-Ac(6)c-Asn-(naphthylpropylamide) platform, where Xxx = the hydrolytically stable pTyr mimetics phosphonomethyl phenylalanine (Pmp) or carboxymethyl phenylalanine (Cmf). The effects of N-alpha-(3-amino)Z derivatization were also investigated for this platform, to ascertain whether the large binding enhancement reported for tripeptides such as pTyr-Ile-Asn-NH2 could be observed. In ELISA-based extracellular Grb2 SH2 domain binding assays, it was found for the Pmp-based series, that extending the oxalyl carboxyl out by one methylene unit or replacing carboxyl functionality with a tetrazole isostere, resulted in binding potency greater than the parent N-alpha-acetyl-containing compound, with enhancement approximating that observed for the N-alpha-oxalyl derivative. When Cmf was used as the pTyr mimetic, only modest differences in IC50 values were observed for the series. Examination of the N-alpha-(3-amino)Z derivatized Pmp-Ac(6)c-Asn-(naphthylpropylamide), showed that binding affinity was reduced relative to the parent N-alpha-acetyl analogue, in contrast to the reported significant enhancement of affinity observed with other peptide ligands. Treatment of MDA-453 tumor cells, which are mitogenically driven through erbB-2 tyrosine kinase-dependent pathways, with Pmp-containing inhibitors resulted in growth inhibition, with the N-alpha-oxalyl and N-alpha-malonyl-containing compounds exhibiting IC50 values (4.3 and 4.6 muM, respectively) approximately five-fold lower than the parent N-alpha-acetyl-containing compound. Tetrazole and N-alpha-(3-amino)Z-containing inhibitors were from two- to four-fold less potent than these latter analogues in the growth inhibition assays. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00014-1
• 作为产物：
  描述：

  ethyl 2-(5-(4-methoxybenzyl)tetrazolyl)acetate 在 lithium hydroxide 作用下， 生成 [1-(4-methoxybenzyl)-1H-tetrazol-5-yl]acetic acid
  参考文献：
  名称：

  N-Terminal carboxyl and tetrazole-containing amides as adjuvants to Grb2 SH2 domain ligand binding

  摘要：

  High affinity binding of peptides to Src homology 2 (SH2) domains, often requires the presence of phosphotyrosyl (pTyr) or pTyr-mimicking moieties in the N-terminal position of the binding ligand. Several reports have shown that N-alpha-acylation of the critical pTyr residue can result in increased SH2 domain binding potency. For Grb2 SH2 domains which recognize pTyr-Xxx-Asn-NH2 motifs, significant potency enhancement can be incurred by N-alpha-(3-amino)Z derivatization of tripeptides such as pTyr-Xxe-Asn-NH2. Using ligands based on the high affinity pY-Ac(6)c-Asn-(naphthylpropylamide) motif, (where Ac(6)c = 1-aminocyclohex-anecarboxylic acid), additional reports have shown moderate potentiating effects of N-alpha-oxalyl derivatization. The current study examined variations of the N-alpha-oxalyl theme in the context of a Xxx-Ac(6)c-Asn-(naphthylpropylamide) platform, where Xxx = the hydrolytically stable pTyr mimetics phosphonomethyl phenylalanine (Pmp) or carboxymethyl phenylalanine (Cmf). The effects of N-alpha-(3-amino)Z derivatization were also investigated for this platform, to ascertain whether the large binding enhancement reported for tripeptides such as pTyr-Ile-Asn-NH2 could be observed. In ELISA-based extracellular Grb2 SH2 domain binding assays, it was found for the Pmp-based series, that extending the oxalyl carboxyl out by one methylene unit or replacing carboxyl functionality with a tetrazole isostere, resulted in binding potency greater than the parent N-alpha-acetyl-containing compound, with enhancement approximating that observed for the N-alpha-oxalyl derivative. When Cmf was used as the pTyr mimetic, only modest differences in IC50 values were observed for the series. Examination of the N-alpha-(3-amino)Z derivatized Pmp-Ac(6)c-Asn-(naphthylpropylamide), showed that binding affinity was reduced relative to the parent N-alpha-acetyl analogue, in contrast to the reported significant enhancement of affinity observed with other peptide ligands. Treatment of MDA-453 tumor cells, which are mitogenically driven through erbB-2 tyrosine kinase-dependent pathways, with Pmp-containing inhibitors resulted in growth inhibition, with the N-alpha-oxalyl and N-alpha-malonyl-containing compounds exhibiting IC50 values (4.3 and 4.6 muM, respectively) approximately five-fold lower than the parent N-alpha-acetyl-containing compound. Tetrazole and N-alpha-(3-amino)Z-containing inhibitors were from two- to four-fold less potent than these latter analogues in the growth inhibition assays. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00014-1

文献信息

• Medicine for inhibiting drug elimination pump
  申请人：Nakayama Kiyoshi

  公开号：US20050009843A1

  公开（公告）日：2005-01-13

  A medicament for preventive and/or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): wherein, R 1 and R 2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W 1 represents —CH═CH—, —CH 2 O—, —CH 2 CH 2 — or the like; R 3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R 4 represents hydrogen atom, a group of —OZ 0-4 R 5 (Z 0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R 5 represents a cyclic alkyl group, an aryl group or the like); W 2 represents a single bond or —C(R 8 )═C(R 9 )—(R 8 and R 9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W 2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.

  预防和/或治疗微生物感染的药物，其活性成分为以下通用式（I）所表示的化合物：其中，R1和R2表示氢原子、卤原子、羟基或类似物，W1表示—CH═CH—、—CH2O—、—CH2CH2—或类似物；R3表示氢原子、卤原子、羟基或氨基；R4表示氢原子、—OZ0-4R5（Z0-4表示烷基、氟代烷基或单键，R5表示环烷基、芳基或类似物）；W2表示单键或—C（R8）═C（R9）—（R8和R9表示氢原子、卤原子、低烷基或类似物，Q表示酸性基团，但W2和Q可以共同形成乙烯基噻唑烷二酮或等效的杂环环；m和n表示0至2的整数，q表示0至3的整数。
• MEDICINE FOR INHIBITING DRUG ELIMINATION PUMP
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1389463A1

  公开（公告）日：2004-02-18

  A medicament for preventive and/or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): wherein, R1 and R2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W1 represents -CH=CH-, -CH2O-, -CH2CH2- or the like; R3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R4 represents hydrogen atom, a group of -OZ0-4R5 (Z0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R5 represents a cyclic alkyl group, an aryl group or the like); W2 represents a single bond or -C(R8)=C(R9)- (R8 and R9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.

  一种用于预防和/或治疗微生物感染的药物，其活性成分包括由以下通式(I)代表的化合物： 其中，R1 和 R2 代表氢原子、卤素原子、羟基或类似基团；W1 代表-CH=CH-、-CH2O-、-CH2CH2-或类似基团；R3 代表氢原子、卤素原子、羟基或氨基；R4 代表氢原子、-OZ0-4R5 的基团（Z0-4 代表亚烷基、氟取代的亚烷基或单键，R5 代表环状烷基、芳基或类似基团）；W2 代表单键或-C(R8)＝C(R9)-（R8 和 R9 代表氢原子、卤素原子、低级烷基或类似基团，Q 代表酸性基团，但 W2 和 Q 可共同形成亚乙烯基噻唑烷二酮或等效的杂环；m 和 n 代表 0 至 2 的整数，q 代表 0 至 3 的整数。
• MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: Highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate
  作者：Ken-ichi Yoshida、Kiyoshi Nakayama、Masami Ohtsuka、Noriko Kuru、Yoshihiro Yokomizo、Atsunobu Sakamoto、Makoto Takemura、Kazuki Hoshino、Hiroko Kanda、Hironobu Nitanai、Kenji Namba、Kumi Yoshida、Yuichiro Imamura、Jason Z. Zhang、Ving J. Lee、William J. Watkins

  DOI：10.1016/j.bmc.2007.07.039

  日期：2007.11

  A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, Substituted at the 2-position with piperidines bearing quaternary ammonium salt side chains, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Attachment of the charged entity using an N-ethylcarbamoyloxy linker led to the discovery of the highly soluble compound 22 (D13-9001), which maintained good potency in vitro and displayed excellent activity in vivo in a rat pneumonia model of P. aeruginosa. (C) 2007 Elsevier Ltd. All rights reserved.