methyl 2-((tert-butoxycarbonyl)amino)-2-(3-nitrophenyl)acetate | 188586-91-6

• 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: methyl 2-((tert-butoxycarbonyl)amino)-2-(3-nitrophenyl)acetate
• 英文别名: Methyl [(t-butoxycarbonyl)amino](3-nitrophenyl)acetate；methyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(3-nitrophenyl)acetate
• CAS: 188586-91-6
• 化学式: C₁₄H₁₈N₂O₆
• 分子量: 310.307
• InChiKey: GFVONTHWABMGNL-UHFFFAOYSA-N

物化性质

• 沸点：
  443.7±45.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 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：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-((tert-butoxycarbonyl)amino)-2-(3-nitrophenyl)acetate 在 四丁基溴化铵 、 氢气 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 34.5h， 生成 tert-butyl (2-(1-(2-fluoro-6-(trifluoromethyl)benzyl)-2,4-dioxo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-1H-spiro[furo[3,4-d]pyrimidine-5,4'-piperidin]-3(2H,4H,7H)-yl)-1-(3-(3-methylureido)phenyl)ethyl)carbamate
  参考文献：
  名称：

  [EN] GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  [FR] ANTAGONISTES DES RÉCEPTEURS DE L'HORMONE DE LIBÉRATION DES GONADOTROPHINES, LEUR PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE LES COMPRENANT

  摘要：

  本发明提供了促性腺激素释放激素受体拮抗剂及包括其的药物组合物，可用于预防或治疗与性激素相关的疾病，如子宫内膜异位症、闭经、月经不调、子宫肌瘤、子宫肌瘤、多囊卵巢综合征、红斑狼疮、多毛症、性早熟、身材矮小、痤疮、脱发、性腺类固醇依赖性肿瘤、促性腺激素产生性垂体腺瘤、睡眠呼吸暂停、肠易激综合征、经前综合征、良性前列腺增生、避孕和不孕症，以及阿尔茨海默病。

  公开号：

  WO2013129879A1
• 作为产物：
  描述：

  氨基-(3-硝基-苯基)-乙酸 在 氯化亚砜 、 碳酸氢钠 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 methyl 2-((tert-butoxycarbonyl)amino)-2-(3-nitrophenyl)acetate
  参考文献：
  名称：

  [EN] GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  [FR] ANTAGONISTES DES RÉCEPTEURS DE L'HORMONE DE LIBÉRATION DES GONADOTROPHINES, LEUR PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE LES COMPRENANT

  摘要：

  本发明提供了促性腺激素释放激素受体拮抗剂及包括其的药物组合物，可用于预防或治疗与性激素相关的疾病，如子宫内膜异位症、闭经、月经不调、子宫肌瘤、子宫肌瘤、多囊卵巢综合征、红斑狼疮、多毛症、性早熟、身材矮小、痤疮、脱发、性腺类固醇依赖性肿瘤、促性腺激素产生性垂体腺瘤、睡眠呼吸暂停、肠易激综合征、经前综合征、良性前列腺增生、避孕和不孕症，以及阿尔茨海默病。

  公开号：

  WO2013129879A1

文献信息

• GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：SK CHEMICALS CO., LTD.

  公开号：US20150166558A1

  公开（公告）日：2015-06-18

  Disclosed are a gonadotropin releasing hormone receptor antagonist and a pharmaceutical composition including the same, which can be useful in preventing or treating a sex hormone-related disease such as endometriosis, amenorrhea, irregular menstruation, uterine myoma, uterine fibroids, polycystic ovarian disease, lupus erythematous, hypertrichosis, precocious puberty, short stature, acne, alopecia, gonadal steroid-dependent neoplasms, gonadotropin-producing pituitary adenoma, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hyperplasia, contraception, and infertility, as well as Alzheimer disease.

  揭示了一种促性腺激素释放激素受体拮抗剂和包括该拮抗剂的药物组合物，可用于预防或治疗与性激素相关的疾病，如子宫内膜异位症、闭经、月经不调、子宫肌瘤、子宫纤维瘤、多囊卵巢综合征、红斑狼疮、多毛症、性早熟、身材矮小、痤疮、脱发、性腺类固醇依赖性肿瘤、促性腺激素产生垂体腺瘤、睡眠呼吸暂停、肠易激综合征、经前综合征、良性前列腺增生、避孕和不孕症，以及阿尔茨海默病。
• [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）。
• Design, synthesis and biological evaluation of non-covalent AmpC β-lactamases inhibitors
  作者：Filippo Genovese、Sandra Lazzari、Ettore Venturi、Luca Costantino、Jesus Blazquez、Claudia Ibacache-Quiroga、Maria Paola Costi、Donatella Tondi

  DOI：10.1007/s00044-017-1809-x

  日期：2017.5

  Bacterial resistance represents a worldwide emergency threatening the efficacy of all available antibiotics. Among the several resistance mechanisms developed by bacteria, beta-lactamase enzymes (BLs), which are able to inactivate most beta-lactam core antibiotics, represent a key target to block, thus prolonging antibiotics half-life. Several approaches aimed at inhibiting beta-lactamases have been so far undertaken, mainly involving beta-lactam-like or covalent inhibitors. Applying a structure-based de novo design approach, we recently discovered a novel, non-covalent and competitive inhibitor of AmpC beta-lactamase: lead 1. It has a K-i of 1 mu M, a ligand efficiency of 0.38 kcal mol(-1) and lead-like physical properties. Moreover, it reverts resistance to ceftazidime in bacterial pathogens expressing AmpC and does not up-regulate beta-lactamases expression in cell culture. Its features make it a good candidate for chemical optimization: starting from lead 1 crystallographic complex with AmpC, 11 analogs were designed to complement additional AmpC sites, then synthesized and tested against clinically resistant pathogens. While the new inhibitors maintain similar in vitro activity as the starting lead, some of them, in biological assays, extert a higher potency showing improved synergic activity with ceftazidime in resistant clinically isolated strains.
• Novel Carboxaldehyde Mediated Synthetic Pathway for 5′-Amino Adenosine Analogues
  作者：Garrett S. Gibbons、Hollis D. Showalter、Zaneta Nikolovska-Coleska

  DOI：10.1080/15257770.2014.1001074

  日期：2015.5.4

  Modifications of the 5 '-position of adenosine have been prepared via a novel 5 '-carboxaldehyde synthon. The described methodology should prove useful for making related compounds in which amine-derived moieties off the 5 '-position of adenosine (or related nucleoside congeners) can be easily incorporated via reductive amination, especially for the incorporation of aromatic amines.
• GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS
  申请人：JAMES BLACK FOUNDATION LIMITED

  公开号：EP1178969A1

  公开（公告）日：2002-02-13