(5,6-dichloro-2-indolyl)methanol | 201929-83-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (5,6-dichloro-2-indolyl)methanol
• 英文别名: (5,6-dichloro-1H-indol-2-yl)methanol
• CAS: 201929-83-1
• 化学式: C₉H₇Cl₂NO
• mdl: MFCD09802224
• 分子量: 216.067
• InChiKey: WROJWFRHNGIGNQ-UHFFFAOYSA-N

物化性质

• 沸点：
  427.0±40.0 °C(Predicted)
• 密度：
  1.547±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  36
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (5,6-dichloro-2-indolyl)methanol 在 manganese(IV) oxide 、 sodium hydride 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 反应 49.0h， 生成 (E) 3-(5,6-dichloro-2-indolyl)-2-propen-1-ol
  参考文献：
  名称：

  5-(5,6-Dichloro-2-indolyl)-2-methoxy-2,4-pentadienamides:  Novel and Selective Inhibitors of the Vacuolar H⁺-ATPase of Osteoclasts with Bone Antiresorptive Activity

  摘要：

  The vacuolar H+-ATPase (V-ATPase) located on the ruffled border of the osteoclast, is a proton pump which is responsible for secreting the massive amounts of protons that are required for the bone resorption process. With the aim to identify new agents which are able to prevent the excessive bone resorption associated with osteoporosis, we have designed a novel class of potent and selective inhibitors of the osteoclast proton pump, starting from the structure of the specific V-ATPase inhibitor bafilomycin A(1). Compounds 3a-d potently inhibited the V-ATPase in chicken osteoclast membranes (IC50 = 60-180 nM) and were able to prevent bone resorption by human osteoclasts in vitro at low-nanomolar concentrations. Notably, the EC50 of compound 3c in this assay was 45-fold lower than the concentration required for half-maximal inhibition of the V-ATPase from human kidney cortex. These results support the validity of the osteoclast proton pump as a useful molecular target to produce novel inhibitors of bone resorption, potentially useful as antiosteporotic agents.

  DOI：

  10.1021/jm9800144
• 作为产物：
  描述：

  4,5-二氯-2-硝基甲苯 在 lithium aluminium tetrahydride 、 potassium ethoxide 、 铁粉 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 52.0h， 生成 (5,6-dichloro-2-indolyl)methanol
  参考文献：
  名称：

  5-(5,6-Dichloro-2-indolyl)-2-methoxy-2,4-pentadienamides:  Novel and Selective Inhibitors of the Vacuolar H⁺-ATPase of Osteoclasts with Bone Antiresorptive Activity

  摘要：

  The vacuolar H+-ATPase (V-ATPase) located on the ruffled border of the osteoclast, is a proton pump which is responsible for secreting the massive amounts of protons that are required for the bone resorption process. With the aim to identify new agents which are able to prevent the excessive bone resorption associated with osteoporosis, we have designed a novel class of potent and selective inhibitors of the osteoclast proton pump, starting from the structure of the specific V-ATPase inhibitor bafilomycin A(1). Compounds 3a-d potently inhibited the V-ATPase in chicken osteoclast membranes (IC50 = 60-180 nM) and were able to prevent bone resorption by human osteoclasts in vitro at low-nanomolar concentrations. Notably, the EC50 of compound 3c in this assay was 45-fold lower than the concentration required for half-maximal inhibition of the V-ATPase from human kidney cortex. These results support the validity of the osteoclast proton pump as a useful molecular target to produce novel inhibitors of bone resorption, potentially useful as antiosteporotic agents.

  DOI：

  10.1021/jm9800144

文献信息

• Indole derivatives for the treatment of osteoporosis
  申请人：Smith Kline Beecham SpA

  公开号：US20020173659A1

  公开（公告）日：2002-11-21

  A compound of formula (I): 1 or a salt thereof, or a solvate thereof, wherein Ra represents a group R 5 which is hydrogen, alkyl or optionally substituted aryl and Rb represents a moiety of formula (a): 2 wherein X represents a hydroxy or an alkoxy group wherein the alkyl group may be substituted or unsubstituted or X represents a group NR s R t wherein R s and R t each independently represent hydrogen, alkyl, substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted arylalkyl, an optionally substituted heterocyclic group or an optionally substituted heterocyclylalkyl group, or R s and R t together with the nitrogen to which they are attached form a heterocyclic group; RI represents an alkyl or a substituted or unsubstituted aryl group; and R 2 , R 3 and R 4 each independently represent hydrogen, alkyl, aryl or substituted aryl R 6 and R 7 each independently represents hydrogen, hydroxy, amino, alkoxy, optionally substituted aryloxy, optionally substituted benzyloxy, alkylamino, dialkylamino, halo, trifluoromethyl, trifluoromethoxy, nitro, alkyl, carboxy, carbalkoxy, carbamoyl, alkylcarbamoyl, or R 6 and R 7 together represent methylenedioxy, carbonyldioxy or carbonyldiamino; and R 8 represents hydrogen, hydroxy, alkanoyl, alkyl, aminoalkyl, hydroxyalkyl, carboxyalkyl, carbalkoxyalkyl, carbamoyl or aminosulphonyl; a process for preparing such a compound, a pharmaceutical composition containing such a compound and the use of such a compound in medicine

  式（I）的化合物：1或其盐，或其溶剂化物，其中Ra代表一个R5基团，该基团是氢，烷基或可选取代芳基，Rb代表式（a）的一个基团：2其中X代表羟基或烷氧基，其中烷基可能是取代或未取代的，或者X代表羰基-NRsRt，其中Rs和Rt各自独立地代表氢，烷基，取代烷基，可选取代烯基，可选取代芳基，可选取代芳基烷基，可选取代杂环基或可选取代杂环基烷基，或Rs和Rt与它们所连接的氮一起形成杂环基；RI代表烷基或取代或未取代的芳基基团；R2、R3和R4各自独立地代表氢，烷基，芳基或取代芳基；R6和R7各自独立地代表氢，羟基，氨基，烷氧基，可选取代芳氧基，可选取代苯甲氧基，烷基氨基，二烷基氨基，卤素，三氟甲基，三氟甲氧基，硝基，烷基，羧基，羰基氧基，氨基甲酰基，烷基氨甲酰基，或R6和R7一起代表亚甲二氧基，羰基二氧基或羰基二氨基；以及R8代表氢，羟基，烷酰基，烷基，氨基烷基，羟基烷基，羧基烷基，羰基氧基烷基，氨甲酰基或氨基磺酰基；一种制备这样的化合物的方法，包含这样的化合物的制药组合物以及这样的化合物在医学上的用途。
• INDOLE DERIVATIVES FOR THE TREATMENT OF OSTEOPOROSIS
  申请人：Smithkline Beecham S.p.A.

  公开号：EP0914321A1

  公开（公告）日：1999-05-12
• US6903117B2
  申请人：——

  公开号：US6903117B2

  公开（公告）日：2005-06-07
• [EN] INDOLE DERIVATIVES FOR THE TREATMENT OF OSTEOPOROSIS<br/>[FR] DERIVES D'INDOLE POUR LE TRAITEMENT DE L'OSTEOPOROSE
  申请人：SMITHKLINE BEECHAM S.P.A.

  公开号：WO1998001443A1

  公开（公告）日：1998-01-15

  (EN) A compound of formula (I), or a salt thereof, or a solvate thereof, wherein Ra represents a group R5 which is hydrogen, alkyl or optionally substituted aryl and Rb represents a moiety of formula (a), wherein X represents a hydroxy or an alkoxy group wherein the alkyl group may be substitued or unsubstituted or X represents a group NRsRt wherein Rs and Rt each independently represent hydrogen, alkyl, substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted arylalkyl, an optionally substituted heterocyclic group or an optionally substituted heterocyclylalkyl group, or Rs and Rt together with the nitrogen to which they are attached form a heterocyclic group; R1 represents an alkyl or a substituted or unsubstituted aryl group; and R2, R3 and R4 each independently represent hydrogen, alkyl, aryl or substituted aryl; R6 and R7 each independently represent hydrogen, hydroxy, amino, alkoxy, optionally substituted aryloxy, optionally substituted benzyloxy, alkylamino, dialkylamino, halo, trifluoromethyl, trifluoromethoxy, nitro, alkyl, carboxy, carbalkoxy, carbamoyl, alkylcarbamoyl, or R6 and R7 together represent methylenedioxy, carbonyldioxy or carbonyldiamino; and R8 represents hydrogen, hydroxy, alkynoyl, alkyl, aminoalkyl, hydroxyalkyl, carboxyalky, carbalkoxyalkyl, carbamoyl or aminosulphonyl; a process for preparing such a compound, a pharmaceutical composition containing such a compound and the use of such a compound in medecine.(FR) Composé ou sel ou solvate défini par la formule (I), dans laquelle Ra représente un groupe R5 qui est l'hydrogène, l'alkyle ou éventuellement l'aryle substitué, et Rb représente une fraction définie par la formule (a), dans laquelle X représente un groupe hydroxy ou un groupe alkoxy dans lesquels le groupe alkyle peut être substitué ou non substitué, ou X représente un groupe NRsRt dans lequel Rs et Rt représentent chacun indépendamment l'hydrogène, l'alkyle, l'alkyle substitué, l'alcényle éventuellement substitué, l'aryle éventuellement substitué, l'arylalkyle éventuellement substitué, un groupe hétérocyclique éventuellement substitué ou un groupe hétérocyclylalkyle éventuellement substitué; R1 représente un alkyle ou un groupe aryle substitué ou non substitué; et R2, R3 et R4 représentent chacun indépendamment l'hydrogène, alkyle, aryle ou aryle substitué; R6 et R7 représentent chacun indépendamment l'hydrogène, hydroxy, amino, alcoxy, aryloxy éventuellement substitué, benzyloxy éventuellement substitué, alkylamino, dialkylamino, halo, trifluorométhyle, trifluorométhoxy, nitro, alkyle, carboxy, carbalkoxy, carbamyle, alkylcarbymyle, ou R6 et R7 représentent ensemble le méthylènedioxy, carbonyldioxy ou carbonyldiamino; et R8 représente l'hydrogène, hydroxy, alkanoyle, alkyle, aminoalkyle, carboxyalkyle, carbalkoxyalkyle, carbamyle ou aminosulphonyle; procédé pour préparer un tel composant, composition pharmaceutique contenant ce composant et utilisation médicale de ce composant.
• 5-(5,6-Dichloro-2-indolyl)-2-methoxy-2,4-pentadienamides:  Novel and Selective Inhibitors of the Vacuolar H⁺-ATPase of Osteoclasts with Bone Antiresorptive Activity
  作者：Stefania Gagliardi、Guy Nadler、Emanuela Consolandi、Carlo Parini、Marcel Morvan、Marie-Nöelle Legave、Pietro Belfiore、Andrea Zocchetti、Geoffrey D. Clarke、Ian James、Ponnal Nambi、Maxine Gowen、Carlo Farina

  DOI：10.1021/jm9800144

  日期：1998.5.1

  The vacuolar H+-ATPase (V-ATPase) located on the ruffled border of the osteoclast, is a proton pump which is responsible for secreting the massive amounts of protons that are required for the bone resorption process. With the aim to identify new agents which are able to prevent the excessive bone resorption associated with osteoporosis, we have designed a novel class of potent and selective inhibitors of the osteoclast proton pump, starting from the structure of the specific V-ATPase inhibitor bafilomycin A(1). Compounds 3a-d potently inhibited the V-ATPase in chicken osteoclast membranes (IC50 = 60-180 nM) and were able to prevent bone resorption by human osteoclasts in vitro at low-nanomolar concentrations. Notably, the EC50 of compound 3c in this assay was 45-fold lower than the concentration required for half-maximal inhibition of the V-ATPase from human kidney cortex. These results support the validity of the osteoclast proton pump as a useful molecular target to produce novel inhibitors of bone resorption, potentially useful as antiosteporotic agents.