4-formylphenylaminoacetic acid ethyl ester | 875803-07-9

• 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: 4-formylphenylaminoacetic acid ethyl ester
• 英文别名: ethyl 2-(4-formylphenylamino)acetate；ethyl 2-(4-formylanilino)acetate
• CAS: 875803-07-9
• 化学式: C₁₁H₁₃NO₃
• 分子量: 207.229
• InChiKey: KIAPTEQXIVHCOL-UHFFFAOYSA-N

物化性质

• 熔点：
  90-92 °C(Solv: dichloromethane (75-09-2))
• 沸点：
  343.0±22.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-formylphenylaminoacetic acid ethyl ester 在 哌啶 、 sodium dithionite 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 {[4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-phenyl]-formyl-amino}-acetic acid ethyl ester
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of 1-,3-,8-, and 9-Substituted-9-deazaxanthines at the Human A_2B Adenosine Receptor

  摘要：

  Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for their binding affinity at the recombinant human adenosine receptors, in particular at the hA(2B) and hA(2A) subtypes. Several ligands endowed with sub-micromolar to low nanomolar binding affinity at hA(2B) receptors, good selectivity over hA(2A) and hA(3), but a relatively poor selectivity over hA(1) were obtained. Good antagonistic potencies and efficacies, with pA(2) values close to the corresponding pK(i)s, were observed in functional assays in vitro performed on a selected series of compounds. 1,3-Dimethyl-8-phenoxy-(N-p-halogenophenyl)-acetamido-9-deazaxanthine derivatives appeared as the most interesting leads, some of them showing outstanding hA(2B) affinities, high selectivity over hA(2A) and hA(3), but low selectivity over hA(1). Structure-affinity relationships suggested that the binding potency at the hA(2B) receptor was mainly modulated by the steric (lipophilic) properties of the substituents at positions 1 and 3 and by the electronic and lipophilic characteristics of the substituents at position 8. A comparison among affinity and selectivity profiles of 9-deazaxanthines with the corresponding xanthines suggested some possible differences in their binding mode.

  DOI：

  10.1021/jm0506221
• 作为产物：
  描述：

  对氨基苯甲醛 、 溴乙酸乙酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 以58%的产率得到4-formylphenylaminoacetic acid ethyl ester
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of 1-,3-,8-, and 9-Substituted-9-deazaxanthines at the Human A_2B Adenosine Receptor

  摘要：

  Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for their binding affinity at the recombinant human adenosine receptors, in particular at the hA(2B) and hA(2A) subtypes. Several ligands endowed with sub-micromolar to low nanomolar binding affinity at hA(2B) receptors, good selectivity over hA(2A) and hA(3), but a relatively poor selectivity over hA(1) were obtained. Good antagonistic potencies and efficacies, with pA(2) values close to the corresponding pK(i)s, were observed in functional assays in vitro performed on a selected series of compounds. 1,3-Dimethyl-8-phenoxy-(N-p-halogenophenyl)-acetamido-9-deazaxanthine derivatives appeared as the most interesting leads, some of them showing outstanding hA(2B) affinities, high selectivity over hA(2A) and hA(3), but low selectivity over hA(1). Structure-affinity relationships suggested that the binding potency at the hA(2B) receptor was mainly modulated by the steric (lipophilic) properties of the substituents at positions 1 and 3 and by the electronic and lipophilic characteristics of the substituents at position 8. A comparison among affinity and selectivity profiles of 9-deazaxanthines with the corresponding xanthines suggested some possible differences in their binding mode.

  DOI：

  10.1021/jm0506221

文献信息

• [EN] HYPOPHOSPHOROUS ACID DERIVATIVES HAVING ANTIHYPERALGIC ACTIVITY AND BIOLOGICAL APPLICATIONS THEREOF<br/>[FR] DÉRIVÉS DE L'ACIDE HYPOPHOSPHOREUX AYANT UNE ACTIVITÉ ANTIHYPERALGIQUE ET LEURS APPLICATIONS BIOLOGIQUES
  申请人：UNIV PARIS DESCARTES

  公开号：WO2012156931A1

  公开（公告）日：2012-11-22

  The invention relates to hypophosphorous acid derivatives of formula (I) wherein - X is H or OH, - R represents one or several radicals R1-R5, identical or different, two of R1-R5 optionally occupying the same position on the phenyl group, one to four of R1-R5 being H and the others being selected in the group comprising - 0-(CH2)n-COOH; - S-(CH2)n-COOH; -NH-(CH2)n-COOH; - 0-(CH,R') -COOH; -O- (CH2)n-OH; OR', -R' being a C1 -C3 alkyl radical;-OH; --COOH; halogen, particularly -F, - CI, -Br, -I, -CF3; -OCF3; -N02; -CH=CH-COOH; - -(CH2)n-COOH; O - (CH2)n- P03H2; O - (CF2)n- P03H2; O - (CH2)n- S03H; O - (CH2)n- CONHOH; O - (CH2)n-tetrazol; O - (CH2)n-hydroxyisoxazol - n = 1 to 5, preferably 1-3; said hypophosrous acid derivatives being diastereoisomers or enantiomers.

  该发明涉及式(I)的次磷酸衍生物，其中- X为H或OH，- R代表一个或几个基团R1-R5，相同或不同，R1-R5中的两个可以选择占据苯基上的同一位置，R1-R5中的一到四个为H，其余的选择自-0-(CH2)n-COOH；-S-(CH2)n-COOH；-NH-(CH2)n-COOH；-0-(CH,R')-COOH；-O-(CH2)n-OH；OR'，其中-R'为C1-C3烷基基团；-OH；-COOH；卤素，特别是-F，-Cl，-Br，-I，-CF3；-OCF3；-NO2；-CH=CH-COOH；-(CH2)n-COOH；O-(CH2)n-P03H2；O-(CF2)n-P03H2；O-(CH2)n-S03H；O-(CH2)n-CONHOH；O-(CH2)n-四唑；O-(CH2)n-羟基异噁唑-n=1至5，优选1-3；所述的次磷酸衍生物为对映异构体或对映体。
• HYPOPHOSPHOROUS ACID DERIVATIVES HAVING ANTIHYPERALGIC ACTIVITY AND BIOLOGICAL APPLICATIONS THEREOF
  申请人：Acher Francine

  公开号：US20140107078A1

  公开（公告）日：2014-04-17

  The invention relates to hypophosphorous acid derivatives of formula (I) wherein —X is H or OH, —R represents one or several radicals R 1 -R 5 , identical or different, two of R 1 -R 5 optionally occupying the same position on the phenyl group, one to four of R 1 -R 5 being H and the others being selected in the group comprising -0-(CH 2 ) n —COOH; —S—(CH 2 ) n —COOH; —NH—(CH 2 ) n —COOH; -0-(CH,R′)—COOH; —O—(CH 2 ) n —OH; OR′, —R′ being a C 1 -C 3 alkyl radical; —OH; —COOH; halogen, particularly —F, —CI, —Br, —I, —CF 3 ; —OCF 3 ; —N0 2 ; —CH═CH—COOH; —(CH 2 ) n —COOH; O—(CH 2 ) n —P0 3 H 2 ; O—(CF 2 ) n —P0 3 H 2 ; O—(CH 2 ) n —S0 3 H; O—(CH 2 ) n —CONHOH; O—(CH 2 ) n -tetrazol; O—(CH 2 ) n -hydroxyisoxazol—n=1 to 5, preferably 1-3; said hypophosrous acid derivatives being diastereoisomers or enantiomers.

  本发明涉及公式（I）的亚磷酸衍生物，其中—X为H或OH，—R代表一个或多个基团R1-R5，相同或不同，其中R1-R5中的两个可选择占据苯基上的相同位置，其中一到四个R1-R5是H，其余的被选在包括-0-（CH2）n-COOH；—S-（CH2）n-COOH；—NH-（CH2）n-COOH；-0-（CH，R′）-COOH；—O-（CH2）n-OH；OR′，其中R′是C1-C3烷基基团；—OH；—COOH；卤素，特别是—F，—CI，—Br，—I，—CF3；—OCF3；—N02；—CH═CH—COOH；—（CH2）n-COOH；O-（CH2）n-P03H2；O-（CF2）n-P03H2；O-（CH2）n-S03H；O-（CH2）n-CONHOH；O-（CH2）n-四唑；O-（CH2）n-羟基异噁唑-n=1至5，优选1-3；所述亚磷酸衍生物为对映异构体或对映体。
• Hypophosphorous acid derivatives having antihyperalgic activity and biological applications thereof
  申请人：Acher Francine

  公开号：US09212196B2

  公开（公告）日：2015-12-15

  The invention relates to hypophosphorous acid derivatives of formula (I) wherein —X is H or OH, —R represents one or several radicals R1-R5, identical or different, two of R1-R5 optionally occupying the same position on the phenyl group, one to four of R1-R5 being H and the others being selected in the group comprising -0-(CH2)n—COOH; —S—(CH2)n—COOH; —NH—(CH2)n—COOH; -0-(CH,R′)—COOH; —O—(CH2)n—OH; OR′, —R′ being a C1-C3 alkyl radical; —OH; —COOH; halogen, particularly —F, —CI, —Br, —I, —CF3; —OCF3; —N02; —CH═CH—COOH; —(CH2)n—COOH; O—(CH2)n—P03H2; O—(CF2)n—P03H2; O—(CH2)n—S03H; O—(CH2)n—CONHOH; O—(CH2)n-tetrazol; O—(CH2)n-hydroxyisoxazol—n=1 to 5, preferably 1-3; said hypophosrous acid derivatives being diastereoisomers or enantiomers.

  本发明涉及式(I)的亚磷酸衍生物，其中-X为H或OH，-R代表一个或几个基团R1-R5，相同或不同，其中R1-R5中的两个可以选择占据苯基上的同一位置，R1-R5中的1-4个为H，其余的被选择在包括-0-(CH2)n-COOH；-S-(CH2)n-COOH；-NH-(CH2)n-COOH；-0-(CH，R′)-COOH；-O-(CH2)n-OH；OR′；-R′为C1-C3烷基基团；-OH；-COOH；卤素，特别是-F，-CI，-Br，-I，-CF3；-OCF3；-N02；-CH═CH-COOH；-(CH2)n-COOH；O-(CH2)n-P03H2；O-(CF2)n-P03H2；O-(CH2)n-S03H；O-(CH2)n-CONHOH；O-(CH2)n-四唑；O-(CH2)n-羟基异噁唑-n=1-5，优选1-3；所述亚磷酸衍生物为对映异构体或对映体。
• US9212196B2
  申请人：——

  公开号：US9212196B2

  公开（公告）日：2015-12-15
• Design, Synthesis, and Structure−Activity Relationships of 1-,3-,8-, and 9-Substituted-9-deazaxanthines at the Human A_2B Adenosine Receptor
  作者：Angelo Carotti、Maria Isabel Cadavid、Nuria B. Centeno、Cristina Esteve、Maria Isabel Loza、Ana Martinez、Rosa Nieto、Enrique Raviña、Ferran Sanz、Victor Segarra、Eddy Sotelo、Angela Stefanachi、Bernat Vidal

  DOI：10.1021/jm0506221

  日期：2006.1.1

  Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for their binding affinity at the recombinant human adenosine receptors, in particular at the hA(2B) and hA(2A) subtypes. Several ligands endowed with sub-micromolar to low nanomolar binding affinity at hA(2B) receptors, good selectivity over hA(2A) and hA(3), but a relatively poor selectivity over hA(1) were obtained. Good antagonistic potencies and efficacies, with pA(2) values close to the corresponding pK(i)s, were observed in functional assays in vitro performed on a selected series of compounds. 1,3-Dimethyl-8-phenoxy-(N-p-halogenophenyl)-acetamido-9-deazaxanthine derivatives appeared as the most interesting leads, some of them showing outstanding hA(2B) affinities, high selectivity over hA(2A) and hA(3), but low selectivity over hA(1). Structure-affinity relationships suggested that the binding potency at the hA(2B) receptor was mainly modulated by the steric (lipophilic) properties of the substituents at positions 1 and 3 and by the electronic and lipophilic characteristics of the substituents at position 8. A comparison among affinity and selectivity profiles of 9-deazaxanthines with the corresponding xanthines suggested some possible differences in their binding mode.