d,l-5,7-dihydroxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline | 65510-99-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: d,l-5,7-dihydroxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline
• 英文别名: 5,7-dihydroxy-2-methyl-2,3-dihydroquinolin-4(1H)-one；5,7-dihydroxy-2-methyl-2,3-dihydro-1H-quinolin-4-one；dl-5,7-dihydroxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline；d,l-5,7-Dihydroxy-2-methyl-4-oxo-1,2,3,4-tetrahydrochinolin；(-)-2,3-Dihydro-5,7-dihydroxy-2-methyl-4-quinolone；5,7-dihydroxy-2-methyl-2,3-dihydro-1H-quinolin-4-one
• CAS: 65510-99-8；65511-02-6；65511-03-7
• 化学式: C₁₀H₁₁NO₃
• 分子量: 193.202
• InChiKey: BNEPFPNDLPNULY-UHFFFAOYSA-N

物化性质

• 沸点：
  448.2±40.0 °C(Predicted)
• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  d,l-5,7-dihydroxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline 在 oxone 、 溴化铵 、 zinc(II) chloride 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 6-bromo-8-(6-(3-ethyl-5,7-dihydroxy-8-methyl-4-chromanone)methyl)-5,7-dihydroxy-2-methyl-2,3-dihydroquinolin-4(1H)-one
  参考文献：
  名称：

  Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis

  摘要：

  This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pH(IB)) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pH(IB) to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pK(a) value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pH(IB), and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.

  DOI：

  10.1021/acsinfecdis.8b00325
• 作为产物：
  描述：

  3,5-二甲氧基苯胺 在 氢溴酸 、 溶剂黄146 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 为溶剂， 反应 62.0h， 生成 d,l-5,7-dihydroxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline
  参考文献：
  名称：

  具有抑制结核分枝杆菌活性的新型二苯甲基 类化合物

  摘要：

  本发明涉及具有抑制结核分枝杆菌活性的新型二苯甲基类衍生物及其制备方法，特别是具有抑制复制性和非复制性结核分枝杆菌活性的新型二苯甲基类衍生物及其制备方法。具体地，本发明涉及式(I)所示的化合物或其所有可能的异构体、前药、可药用盐、溶剂合物或水合物，其中各变量如说明书所述。还涉及本发明化合物的制备方法、包含本发明化合物的药物组合物、以及本发明化合物在制备抗结核分枝杆菌感染引起的疾病的药物中的用途。

  公开号：

  CN109293493B

文献信息

• 具有抑制结核分枝杆菌活性的新型二苯甲基 类化合物
  申请人：清华大学

  公开号：CN109293493B

  公开（公告）日：2021-08-03

  本发明涉及具有抑制结核分枝杆菌活性的新型二苯甲基类衍生物及其制备方法，特别是具有抑制复制性和非复制性结核分枝杆菌活性的新型二苯甲基类衍生物及其制备方法。具体地，本发明涉及式(I)所示的化合物或其所有可能的异构体、前药、可药用盐、溶剂合物或水合物，其中各变量如说明书所述。还涉及本发明化合物的制备方法、包含本发明化合物的药物组合物、以及本发明化合物在制备抗结核分枝杆菌感染引起的疾病的药物中的用途。
• Oximino-1-hydroxyoctahydrobenzo[c]quinolines and derivatives thereof
  申请人：Pfizer Inc.

  公开号：US04309545A1

  公开（公告）日：1982-01-05

  9-Amino-1-hydroxyoctahydrobenzo[c]quinoline derivatives of formula ##STR1## and pharmaceutically acceptable acid addition salts thereof wherein R is hydrogen, COR.sub.7 or SO.sub.2 R.sub.8 where R.sub.7 is hydrogen, alkyl, having from one to five carbon atoms; alkenyl and alkynyl each having from two to six carbon atoms; trifluoromethyl, benzyl, furyl, thienyl, pyridyl or R.sub.9 C.sub.6 H.sub.4 where R.sub.9 is H, NH.sub.2, F, Cl, Br, CH.sub.3 or OCH.sub.3 ; R.sub.8 is alkyl having from one to five carbon atoms or R.sub.9 C.sub.6 H.sub.4 ; R.sub.1 is hydrogen, benzyl, benzoyl, alkanoyl having from one to five carbon atoms or --CO--(CH.sub.2).sub.p --NR.sub.2 R.sub.3 wherein p is 0 or an integer from 1 to 4; each of R.sub.2 and R.sub.3 when taken individually is hydrogen or alkyl having from one to four carbon atoms; R.sub.2 and R.sub.3 when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring selected from piperidino, pyrrolo, pyrrolidino, morpholino or N-alkylpiperazino having from one to four carbon atoms in the alkyl group; R.sub.4 is hydrogen, alkyl having from 1 to 6 carbon atoms or --(CH.sub.2).sub.z --C.sub.6 H.sub.5 wherein z is an integer from 1 to 4; R.sub.5 is hydrogen, methyl or ethyl; R.sub.6 is hydrogen, --(CH.sub.2).sub.y -carbalkoxy having from one to four carbon atoms in the alkoxy group and wherein y is 0 or an integer from 1 to 4, carbobenzyloxy, formyl, alkanoyl having from two to five carbon atoms, alkyl having from one to six carbon atoms; --(CH.sub.2).sub.x --C.sub.6 H.sub.5 wherein x is an integer from 1 to 4; or --CO(CH.sub.2).sub.x-1 --C.sub.6 H.sub.5 ; Z is (a) alkylene having from one to nine carbon atoms; (b) -(alk.sub.1).sub.m -X-(alk.sub.2).sub.n - wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to nine carbon atoms, with the proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not greater than nine; each of m and n is 0 or 1; X is O, S, SO and SO.sub.2 ; and W is hydrogen, methyl, pyridyl, piperidyl, ##STR2## wherein W.sub.1 is selected from the group consisting of hydrogen, fluoro and chloro; and ##STR3## wherein W.sub.2 is hydrogen or ##STR4## is an integer from 1 to 5 and b is 0 or an integer from 1 to 5; with the proviso that the sum of a and b is not greater than 5; useful in mammals as analgesics, tranquilizers, antiemetic agents, diuretics, anticonvulsants, antidiarrheals, antitussives, in treatment of glaucoma, and intermediates therefore.

  9-氨基-1-羟基八氢苯并[c]喹啉衍生物的化学式为##STR1##及其药学上可接受的酸盐，其中R为氢、COR.sub.7或SO.sub.2R.sub.8，其中R.sub.7为氢、烷基，具有1至5个碳原子；烯基和炔基，每个具有2至6个碳原子；三氟甲基、苄基、呋喃基、噻吩基、吡啶基或R.sub.9C.sub.6H.sub.4，其中R.sub.9为H、NH.sub.2、F、Cl、Br、CH.sub.3或OCH.sub.3；R.sub.8为具有1至5个碳原子的烷基或R.sub.9C.sub.6H.sub.4；R.sub.1为氢、苄基、苯甲酰基、具有1至5个碳原子的烷酰基或--CO--(CH.sub.2).sub.p--NR.sub.2R.sub.3，其中p为0或1至4的整数；当单独考虑R.sub.2和R.sub.3时，R.sub.2和R.sub.3分别为氢或具有1至4个碳原子的烷基；当R.sub.2和R.sub.3与它们连接的氮一起形成选自哌啶基、吡咯基、吡咯啉基、吗啉基或N-烷基哌嗪基的5-或6元杂环时，R.sub.2和R.sub.3；R.sub.4为氢、具有1至6个碳原子的烷基或--(CH.sub.2).sub.z--C.sub.6H.sub.5，其中z为1至4的整数；R.sub.5为氢、甲基或乙基；R.sub.6为氢、--(CH.sub.2).sub.y-羧烷氧基，其中羧烷氧基中有1至4个碳原子，y为0或1至4的整数，羧苄氧基、甲酰基、具有2至5个碳原子的烷酰基、具有1至6个碳原子的烷基；--(CH.sub.2).sub.x--C.sub.6H.sub.5，其中x为1至4的整数；或--CO(CH.sub.2).sub.x-1--C.sub.6H.sub.5；Z为(a)具有1至9个碳原子的烷基；(b)-(alk.sub.1).sub.m-X-(alk.sub.2).sub.n-其中(alk.sub.1)和(alk.sub.2)均为具有1至9个碳原子的烷基，但要求(alk.sub.1)加(alk.sub.2)中的碳原子总和不大于9；m和n均为0或1；X为O、S、SO和SO.sub.2；W为氢、甲基、吡啶基、哌啶基，##STR2##其中W.sub.1选自羟基、氟和氯；以及##STR3##其中W.sub.2为氢或##STR4##为1至5的整数，b为0或1至5的整数；但要求a和b的总和不大于5；在哺乳动物中作为止痛药、镇静剂、抗恶心药、利尿剂、抗癫痫药、止泻药、镇咳药、治疗青光眼和其中间体时有用。
• 1,9-Dihydroxyoctahydrobenzo[c]quinolines and
  申请人：Pfizer Inc.

  公开号：US04228169A1

  公开（公告）日：1980-10-14

  1,9-Dihydroxyoctahydro[c]quinolines (I) and 1-hydroxyhexahydrobenzo[c]quinoline-9(8H)-ones (II), useful as antiemetic agents and derivatives thereof having the formulae ##STR1## wherein R is hydroxy or alkanoyloxy having from one to five carbon atoms; R.sub.1 is hydrogen, benzyl, benzoyl, alkanoyl having from one to five carbon atoms or --CO--(CH.sub.2).sub.p --NR.sub.2 R.sub.3 wherein p is 0 or an integer from 1 to 4; each of R.sub.2 and R.sub.3 when taken individually is hydrogen or alkyl having from one to four carbon atoms; R.sub.2 and R.sub.3 when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring (piperidino, pyrrolo, pyrrolidino, morpholino and N-alkylpiperazino having from one to four carbon atoms in the alkyl group); R.sub.4 is hydrogen, alkyl having from 1 to 6 carbon atoms and --(CH.sub.2).sub.z --C.sub.6 H.sub.5 wherein z is an integer from 1 to 4; R.sub.5 is hydrogen, methyl or ethyl; R.sub.6 is hydrogen, --(CH.sub.2).sub.y --carbalkoxy having from 1 to 4 carbon atoms in the alkoxy group wherein y is 0 or an integer from 1 to 4; carbobenzyloxy, formyl, alkanoyl having from two to five carbon atoms, alkyl having from one to six carbon atoms; --(CH.sub.2).sub.x --C.sub.6 H.sub.5 wherein x is an integer from 1 to 4; and --CO(CH.sub.2).sub.x-1 --C.sub.6 H.sub.5 ; Z is (a) alkylene having from one to nine carbon atoms; (b) --(alk.sub.1).sub.m --X--(alk.sub.2).sub.n -- wherein each of (alk.sub.1) and (alk.sub.2) is alkylene having from one to nine carbon atoms, with the proviso that the summation of carbon atoms in (alk.sub.1) plus (alk.sub.2) is not greater than 9; each of m and n is 0 or 1; X is O, S, SO or SO.sub.2 ; and W is hydrogen, methyl, ##STR2## wherein W.sub.1 is hydrogen, chloro or fluoro; pyridyl, piperidyl, cycloalkyl having from 3 to 7 carbon atoms, or monosubstituted cycloalkyl wherein the substituent is ##STR3## wherein W.sub.2 is hydrogen, chloro or fluoro; and pharmaceutically-acceptable acid addition salts of compounds of formulae I and II and the ketals of compounds of formula II wherein the ketal moiety has from two to four carbon atoms.

  1,9-二羟基八氢[c]喹啉（I）和1-羟基六氢苯[c]喹啉-9（8H）-酮（II）及其衍生物，可作为抗恶心剂。其中，I和II的化学式如下：##STR1## 其中，R为羟基或烷酰氧，烷基含有1至5个碳原子；R1为氢、苯甲基、苯甲酰基、烷酰基，烷基含有1至5个碳原子，或--CO--（CH2）p--NR2R3，其中p为0或1至4的整数；当单独考虑R2和R3时，它们分别为氢或烷基，烷基含有1至4个碳原子；当将R2和R3与它们附着的氮一起取出时，它们与氮形成5或6元杂环环（哌啶、吡咯、吡咯烷、吗啉和N-烷基哌嗪，其中烷基含有1至4个碳原子）；R4为氢、烷基含有1至6个碳原子和--（CH2）z--C6H5，其中z为1至4的整数；R5为氢、甲基或乙基；R6为氢、--（CH2）y--羧基烷氧基，烷氧基含有1至4个碳原子，其中y为0或1至4的整数；羧苄氧基、甲酰基、烷酰基，烷基含有2至5个碳原子，烷基含有1至6个碳原子；--（CH2）x--C6H5，其中x为1至4的整数；和--CO（CH2）x-1--C6H5；Z为（a）烷基，含有1至9个碳原子；（b）--（烷基1）m--X--（烷基2）n--，其中（烷基1）和（烷基2）均为含有1至9个碳原子的烷基，但须满足（烷基1）加（烷基2）的碳原子总数不大于9；m和n均为0或1；X为O、S、SO或SO2；W为氢、甲基、##STR2## 其中W1为氢、氯或氟；吡啶基、哌啶基、含有3至7个碳原子的环烷基或单取代的环烷基，其中取代基为##STR3## 其中W2为氢、氯或氟；以及I和II的化合物的药学可接受的酸盐和化合物II的醇缩物，其中醇缩基团具有2至4个碳原子。
• JOHNSON, M. R.
  作者：JOHNSON, M. R.

  DOI：——

  日期：——
• 9-Amino-1-hydroxyoctahydrobenzo(c)quinolines and derivatives thereof
  申请人：PFIZER INC.

  公开号：EP0045171B1

  公开（公告）日：1985-02-13