8-nitroisoquinolin-7-ol | 56623-93-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 8-nitroisoquinolin-7-ol
• 英文别名: 7-Hydroxy-8-nitro-isochinolin；7-hydroxy-8-nitroisoquinoline
• CAS: 56623-93-9
• 化学式: C₉H₆N₂O₃
• 分子量: 190.158
• InChiKey: CGGWVNPZEGPHLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-nitroisoquinolin-7-ol 生成 Dimethylthiocarbamic acid
  参考文献：
  名称：

  GIRARD, GERALD R.;BONDINELL, WILLIAM E.;HILLEGASS, LEONARD M.;HOLDEN, KEN+, J. MED. CHEM. , 32,(1989) N, C. 1566-1571

  摘要：

  DOI：
• 作为产物：
  描述：

  7-羟基异喹啉 在 nitronium tetrafluoborate 作用下， 以 环丁砜 为溶剂， 反应 6.0h， 以69%的产率得到8-nitroisoquinolin-7-ol
  参考文献：
  名称：

  Farnesyl pyrophosphate synthase enantiospecificity with a chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501): Synthetic, structural, and modeling studies

  摘要：

  The complex formed from crystallization of human farnesyl pyrophosphate synthase (hFPPS) from a solution of racemic [ 6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501,8), a chiral analog of the anti-osteoporotic drug risedronate, contained the R enantiomer in the enzyme active site. This enantiospecificity was assessed by computer modeling of inhibitor-active site interactions using Autodock 3, which was also evaluated for predictive ability in calculations of the known configurations of risedronate, zoledronate, and minodronate complexed in the active site of hFPPS. In comparison with these structures, the 8 complex exhibited certain differences, including the presence of only one Mg2+, which could contribute to its 100-fold higher IC50. An improved synthesis of 8 is described, which decreases the number of steps from 12 to 8 and increases the overall yield by 17-fold. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.088

文献信息

• Quaternary nitrogen-containing phosphonate compounds, pharmaceutical
  申请人：Procter & Gamble Pharmaceuticals, Inc.

  公开号：US05391743A1

  公开（公告）日：1995-02-21

  The present invention relates to quaternary nitrogen-containing phosphonate compounds, and the pharmaceutically-acceptable salts and esters thereof and having the general structure: ##STR1## wherein R.sup.1, R.sup.2, R.sup.5 and R.sup.8 are defined in claim 1, m and n are integers from 0 to 10; m+n is from 0 to 10; Z is a saturated, unsaturated, or aromatic, monocyclic or polycyclic carbocycle or monocyclic or polycyclic heterocycle containing one or more heteroatoms selected from O, S, or N, wherein at least one heteroatom is a quaternary nitrogen atom; R is COOH; PO.sub.3 H.sub.2 ; SO.sub.3 H; or P(O)(OH)R.sub.4, wherein R.sub.4 is substituted or unsubstituted alkyl of 1-8 carbon atoms; The present invention further relates to pharmaceutical compositions containing a safe and effective amount of a compound of the present invention, and pharmaceutically-acceptable excipients. Finally, the present invention relates to methods for treating or preventing pathological conditions characterized by abnormal calcium and phosphate metabolism such as osteoporosis, rheumatoid arthritis, and osteoarthritis in humans or other mammals and to methods for treating or preventing dental calculus, plaque and gingivitis.

  本发明涉及四元氮含磷酸酯化合物，以及其药学上可接受的盐和酯，具有以下一般结构：其中R.sup.1、R.sup.2、R.sup.5和R.sup.8在权利要求书中定义，m和n是0到10的整数；m+n是0到10；Z是饱和、不饱和或芳香的单环或多环碳环或含有来自O、S或N的一个或多个杂原子的单环或多环杂环，其中至少一个杂原子是四元氮原子；R是COOH；PO.sub.3 H.sub.2；SO.sub.3 H；或P(O)(OH)R.sub.4，其中R.sub.4是1-8个碳原子的取代或未取代的烷基；本发明还涉及含有本发明化合物的安全有效量的药物组合物，以及药学上可接受的赋形剂。最后，本发明涉及治疗或预防由异常的钙和磷代谢所表征的病理状况的方法，如骨质疏松症、类风湿性关节炎和骨关节炎，在人类或其他哺乳动物中治疗或预防牙石、牙菌斑和牙龈炎的方法。
• Thio-substituted cyclic phosphonate compounds, pharmaceutical
  申请人：The Procter & Gamble Company

  公开号：US05763611A1

  公开（公告）日：1998-06-09

  The present invention relates to thio-substituted cyclic phosphonate compounds including bisphosphonates and phosphonoalkylphosphinates, and the pharmaceutically-acceptable salts and esters thereof. The present invention further relates to pharmaceutical compositions containing a safe and effective amount of a compound of the present invention, and pharmaceutically-acceptable excipients. Finally, the present invention relates to methods for treating or preventing pathological conditions characterized by abnormal calcium and phosphate metabolism in humans or other mammals including treating or preventing osteoporosis and arthritis, especially rheumatoid arthritis and osteoarthritis. The compounds may be monocyclic or bicyclic and have the following general structure: ##STR1## wherein (a) X and Y are independently selected from nil, O, S, and N; (b) R is PO.sub.3 H.sub.2 or P(O)(OH)R.sup.4, wherein R.sup.4 is substituted or unsubstituted C.sub.1 -C.sub.8 alkyl; (c) m and n are integers from 0 to 5, and m+n equals 0 to 5; (d) p and q are integers from 0 to 3, and p+q equals 0 to 3; (e) s is an integer from 0 to 2 and when X is nil and m+n=0, s=2; and (f) R.sup.1 and R.sup.2 are selected from various substituents; provided that at least one thio substituent is present.

  本发明涉及硫代取代的环磷酸酯化合物，包括双磷酸酯和磷酸烷基膦酸酯，以及其药学上可接受的盐和酯。本发明还涉及含有本发明化合物的安全有效量和药学上可接受的辅料的制药组合物。最后，本发明涉及用于治疗或预防人类或其他哺乳动物中的异常钙和磷代谢的病理情况的方法，包括治疗或预防骨质疏松症和关节炎，特别是类风湿性关节炎和骨关节炎。这些化合物可以是单环或双环的，具有以下一般结构：##STR1## 其中（a）X和Y分别选自nil、O、S和N；（b）R为PO.sub.3 H.sub.2或P（O）（OH）R.sup.4，其中R.sup.4是取代或未取代的C.sub.1-C.sub.8烷基；（c）m和n是0到5的整数，m+n等于0到5；（d）p和q是0到3的整数，p+q等于0到3；（e）s是0到2的整数，当X为nil且m+n=0时，s=2；（f）R.sup.1和R.sup.2选自各种取代基；要求至少存在一个硫代取代基。
• Quaternary nitrogen-containing phosphonate compounds for treating abnormal calcium and phosphate metabolism as well as dental calculus and plaque
  申请人：Procter & Gamble Pharmaceuticals, Inc.

  公开号：EP0849272A1

  公开（公告）日：1998-06-24

  1. Quaternary nitrogen-containing phosphonates which are useful in treating or prevening disorders of abnormal calcium and phosphate metabolism and the pharmaceutically-acceptable salts and esters thereof, characterised in that they have the general structure: wherein m and n are integers from 0 to 10; m + n is from 0 to 10; (a) Q is a covalent bond or a moiety selected from O, S, NR1; (b) Y is N+(R8)2 or C(R1)2, and when Y is C(R1)2, at least one R2 must be N+(R8)3; (c) Z is a five-membered saturated, unsaturated, or aromatic, monocyclic carbocycle or heterocycle containing one heteroatom, wherein the heteroatom is nitrogen, (d) R is COOH, SO3H,PO3H2 or P(O)(OH)R4, wherein R4 is alkyl of 1-8 carbon atoms, preferably PO3H2; (e) each R1 is selected from SR6; R9SR6; hydrogen, hydroxy; C1-C8 alkyl; -OR3; -CO2R3; -O2CR3; -NR32; -N(R3)C(O)R3, -C(O)N(R3)2; halogen; -C(O)R3; arylalkyl; nitro; aryl, and combinations thereof, preferably SR6, R9SR6, hydrogen, C1-C8 alkyl, - NR3 2 or CO2R3; (f) each R2 is one or more substituents on the Z moiety independently selected from N+(R8)3; SR6; R9SR6; hydrogen; C1-C8 alkyl; -OR3; -CO2R3; -O2CR3; -NR32;-N(R3)C(O)R3; -C(O)N(R3)2; halogen; hydroxy; -C(O)R3; arylalkyl; nitro; aryl, preferably N+(R8)3, SR6, R9SR6, hydrogen, C1-C8 alkyl; -NR3 2, -OR3, -CO2R3; (g) each R1 is independently selected from hydrogen, alkyl having from 1-8 carbon atoms, and R9SR6, preferably hydrogen, R9SR6 or C1-C8 alkyl. (h) R1 is selected from hydrogen; halogen; SR6; R9SR6, amino; hydroxy; and C1-C8 alkyl, preferably hydrogen, SR6; R9SR6; (i) each R6 is independently selected from H; -C(O)R7;-C(S)R7; -C(O)NR72; -C(S)N(R7)2; -C(S)OR7; -C(O)OR7; wherein R7 is hydrogen or C1-C8 alkyl, preferably hydrogen, -C(O)R7, -C(S)R7; (j ) each R8 is independently selected from nil, alkyl having 1-35 carbon atoms, phenyl, benzyl, or R9 SR6; preferably alkyl having 1-35 carbon atoms; (k) R9 is C1-C8 alkyl.

  1.有助于治疗或预防钙和磷酸盐代谢异常紊乱的含季氮的膦酸盐及其药学上可接受的盐和酯，其特征在于它们具有一般结构： 其中 m 和 n 为 0 至 10 的整数；m + n 为 0 至 10； (a) Q 是共价键或选自 O、S、NR1 的分子； (b) Y 是 N+(R8)2 或 C(R1)2，当 Y 是 C(R1)2 时，至少一个 R2 必须是 N+(R8)3； (c) Z 是含有一个杂原子的五元饱和、不饱和或芳香单环碳环或杂环，其中杂原子为氮、 (d) R 是 COOH、SO3H、PO3H2 或 P(O)(OH)R4，其中 R4 是 1-8 个碳原子的烷基，最好是 PO3H2； (e) 每个 R1 选自 SR6、R9SR6、氢、羟基、C1-C8 烷基、-OR3、-CO2R3、-O2CR3、-NR32、-N(R3)C(O)R3、-C(O)N(R3)2、卤素、-C(O)R3、芳烷基、硝基、芳基及其组合，优选 SR6、R9SR6、氢、C1-C8 烷基、-NR3 2 或 CO2R3； (f) 每个 R2 是 Z 分子上的一个或多个取代基，独立选自 N+(R8)3；SR6；R9SR6；氢；C1-C8 烷基；-OR3；-CO2R3；-O2CR3；-NR32；-N(R3)C(O)R3；-C(O)N(R3)2；卤素；羟基；-C(O)R3；芳烷基；硝基；芳基，优选 N+(R8)3、SR6、R9SR6、氢、C1-C8 烷基；-NR3 2、-OR3、-CO2R3； (g) 每个 R1 独立地选自氢、具有 1-8 个碳原子的烷基和 R9SR6，优选氢、R9SR6 或 C1-C8 烷基。 (h) R1 选自氢、卤素、SR6、R9SR6、氨基、羟基和 C1-C8 烷基，优选氢、SR6、R9SR6； (i) 每个 R6 独立选自 H；-C(O)R7；-C(S)R7；-C(O)NR72；-C(S)N(R7)2；-C(S)OR7；-C(O)OR7；其中 R7 是氢或 C1-C8 烷基，优选氢、-C(O)R7、-C(S)R7； (j) 每个 R8 独立选自零、具有 1-35 个碳原子的烷基、苯基、苄基或 R9 SR6；优选具有 1-35 个碳原子的烷基； (k) R9 是 C1-C8 烷基。
• Tetrahydro thiadiazolo isoquinolines: synthesis and inhibition of phenylethanolamine-N-methyltransferase
  作者：Gerald R. Girard、William E. Bondinell、Leonard M. Hillegass、Kenneth G. Holden、Robert G. Pendleton、Irene Uzinskas

  DOI：10.1021/jm00127a027

  日期：1989.7

  A series of 7,8-fused heterocyclic tetrahydroisoquinolines were synthesized and tested as inhibitors of rabbit adrenal phenylethanolamine-N-methyltransferase (PNMT). 6,7,8,9-Tetrahydro[1,2,3]thiadiazolo[5,4-h]isoquinoline 5 (SK&F 86607) was found to be a potent inhibitor of PNMT with an IC50 similar to that of 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (1, SK&F 64139). The isomeric tetrahydro[1,2,3]thiadiazolo[4,5-h]- and tetrahydro[1,2,5]thiadiazolo[3,4-h]isoquinolines, 13 and 20, were also potent PNMT inhibitors. However, substitution of Cl at position 5 (17) resulted in loss of potency similar to the loss observed in the 5-chloro analogue of 1. The 1,2,5 isomer 20 showed only a small drop in activity at 10(-6) M. All of the thiadiazoles were more potent than the 7,8-benzo-fused analogue 36. Fusion of other five-membered heterocyclic ring systems at the 7,8-position, e.g. triazole 22 and imidazoles 24 and 26, resulted in a decrease of PNMT inhibition. The alpha-adrenoreceptor affinities of 1 and 5 were also compared.
• GIRARD, GERALD R.;BONDINELL, WILLIAM E.;HILLEGASS, LEONARD M.;HOLDEN, KEN+, J. MED. CHEM. , 32,(1989) N, C. 1566-1571
  作者：GIRARD, GERALD R.、BONDINELL, WILLIAM E.、HILLEGASS, LEONARD M.、HOLDEN, KEN+

  DOI：——

  日期：——