[(2R)-7-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-yl]methyl 4-methylbenzenesulfonate | 187543-64-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(2R)-7-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-yl]methyl 4-methylbenzenesulfonate
• 英文别名: (R)-7-methoxy-1,4-benzodioxan-2-ylmethyl 4-toluenesulphonate；[(3R)-6-methoxy-2,3-dihydro-1,4-benzodioxin-3-yl]methyl 4-methylbenzenesulfonate
• CAS: 187543-64-2
• 化学式: C₁₇H₁₈O₆S
• 分子量: 350.392
• InChiKey: DKAWDIOUSDRSEF-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(2R)-7-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-yl]methyl 4-methylbenzenesulfonate 在 氢溴酸 作用下， 以 二甲基亚砜 为溶剂， 反应 18.0h， 生成 (S)-3-(Benzylamino-methyl)-2,3-dihydro-benzo[1,4]dioxin-6-ol
  参考文献：
  名称：

  New Generation Dopaminergic Agents. 1. Discovery of a Novel Scaffold Which Embraces the D₂ Agonist Pharmacophore. Structure−Activity Relationships of a Series of 2-(Aminomethyl)chromans

  摘要：

  A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high-and low-affinity agonist states (D-2(High) and D-2(Low), respectively) of the dopamine (DA) D-2 receptor. The 7-hydroxy-2-(aminomethyl)chroman moiety was observed to be the primary D-2 agonist pharmacophore. The 2-methylchroman moiety was discovered to be an entirely novel scaffold which could be used to access the D-2 agonist pharmacophore. Attaching various simple alkyl and arylalkyl side chains to the 7-hydroxy 2-AMC nucleus had significant effects on selectivity for the D-2(High) receptor vs the 5HT(1A) and alpha(1) receptors. A novel DA partial agonist, (R)-(-)-2-(benzylamino)methyl)chroman-7-ol [R-(-)-35c], was identified as having the highest affinity and best selectivity for the D-2(High) receptor vs the alpha(1) and 5HT(1A) receptors. Several regions of the 2-AMC nucleus were modified and recognized as potential sites to modulate the level of intrinsic activity. The global minimum conformer of the 7-hydroxy-2-AMC moiety was identified as fulfilling the McDermed model D-2 agonist pharmacophoric criteria and was proposed as the D-2 receptor-bound conformation. Structure-activity relationships gained from these studies have aided in the synthesis of D-2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo-and hyperdopaminergic activity, without the side effects associated with complete D-2 agonism or antagonism.

  DOI：

  10.1021/jm9703653
• 作为产物：
  描述：

  (R)-5-methoxy-2-(oxiran-2-ylmethoxy)benzaldehyde 在 吡啶 、 sodium carbonate 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 [(2R)-7-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-yl]methyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  New Generation Dopaminergic Agents. 1. Discovery of a Novel Scaffold Which Embraces the D₂ Agonist Pharmacophore. Structure−Activity Relationships of a Series of 2-(Aminomethyl)chromans

  摘要：

  A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high-and low-affinity agonist states (D-2(High) and D-2(Low), respectively) of the dopamine (DA) D-2 receptor. The 7-hydroxy-2-(aminomethyl)chroman moiety was observed to be the primary D-2 agonist pharmacophore. The 2-methylchroman moiety was discovered to be an entirely novel scaffold which could be used to access the D-2 agonist pharmacophore. Attaching various simple alkyl and arylalkyl side chains to the 7-hydroxy 2-AMC nucleus had significant effects on selectivity for the D-2(High) receptor vs the 5HT(1A) and alpha(1) receptors. A novel DA partial agonist, (R)-(-)-2-(benzylamino)methyl)chroman-7-ol [R-(-)-35c], was identified as having the highest affinity and best selectivity for the D-2(High) receptor vs the alpha(1) and 5HT(1A) receptors. Several regions of the 2-AMC nucleus were modified and recognized as potential sites to modulate the level of intrinsic activity. The global minimum conformer of the 7-hydroxy-2-AMC moiety was identified as fulfilling the McDermed model D-2 agonist pharmacophoric criteria and was proposed as the D-2 receptor-bound conformation. Structure-activity relationships gained from these studies have aided in the synthesis of D-2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo-and hyperdopaminergic activity, without the side effects associated with complete D-2 agonism or antagonism.

  DOI：

  10.1021/jm9703653

文献信息

• Antidepressant azaheterocyclylmethyl derivatives of 2,3-dihydro-1,4-benzodioxan
  申请人：Wyeth

  公开号：US20030236241A1

  公开（公告）日：2003-12-25

  Compounds of the formula 1 useful for the treatment of depression and other conditions such as obsessive compulsive disorder, panic attacks, generalized anxiety disorder, sexual dysfunction, eating disorders, addictive disorders caused by ethanol or cocaine abuse and related illnesses.

  该式化合物用于治疗抑郁症和其他疾病，如强迫症、恐慌发作、广泛性焦虑障碍、性功能障碍、进食障碍、由乙醇或可卡因滥用引起的成瘾障碍及相关疾病。
• [EN] HETEROCYCLYLCARBOXAMIDE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS<br/>[FR] DERIVES HETEROCYCLYLCARBOXAMIDES ET LEUR UTILISATION EN TANT QU'AGENTS THERAPEUTIQUES
  申请人：KNOLL AKTIENGESELLSCHAFT

  公开号：WO1997003071A1

  公开（公告）日：1997-01-30

  (EN) Compounds of formula (I), and pharmaceutically acceptable salts thereof in which A is methylene or O; B is methylene or O; g is 0, 1, 2, 3 or 4; R1 is an optional substituent; U is an alkylene chain optionally substituted by one or more alkyl; Q represents a divalent group containing nitrogen atoms; and T represents CO.HET, have utility in the treatment of central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycaemia, constipation, arrhythmia, disorders of the neuroendocrine system, stress, prostatic hypertrophy, and spasticity.(FR) L'invention concerne des composés représentés par la formule (I) ainsi que des sels pharmaceutiquement acceptables de ces composés. Dans la formule (I), A est méthylène ou oxygène, B est méthylène ou oxygène, g vaut 1, 2, 3 ou 4, R1 est un substituant facultatif, U est une chaîne alkylène facultativement substituée par un ou plusieurs alkyles, Q représente un groupe divalent contenant des atomes d'azote et T représente le groupe CO.HET. Lesdits composés s'avèrent utiles dans le traitement des troubles du système nerveux central, tels que la dépression, l'anxiété, les psychoses (schizophrénie, par exemple), les dyskinésies tardives, la maladie de Parkinson, l'obésité, l'hypertension, la maladie de Gilles de la Tourette, les troubles de la sexualité, la toxicomanie, la pharmacodépendance, les troubles cognitifs, la maladie d'Alzheimer, la démence sénile, la psychonévrose obsessionnelle, les crises de panique, les névroses phobiques, les troubles de l'alimentation et l'anorexie, les troubles cardio-vasculaires et cérébro-vasculaires, le diabète sucré non-insulino-dépendant, l'hyperglycémie, la constipation, l'arythmie, les troubles du système neuro-endocrinien, le stress, l'hypertrophie prostatique et la spasticité.

  化合物的公式(I)，以及其中的药学上可接受的盐，其中A是亚甲基或氧原子；B是亚甲基或氧原子；g为0、1、2、3或4；R1是可选的取代基；U是一种可以被一个或多个烷基取代的烷基链；Q代表含有氮原子的二价基团；T代表CO.HET，可用于治疗中枢神经系统疾病，例如抑郁症、焦虑症、精神病（例如精神分裂症）、迟发性运动障碍、帕金森病、肥胖症、高血压、杜雷特综合症、性功能障碍、药物成瘾、药物滥用、认知障碍、阿尔茨海默病、老年性痴呆、强迫症行为、惊恐发作、社交恐惧症、进食障碍和厌食症、心血管和脑血管疾病、非胰岛素依赖性糖尿病、高血糖、便秘、心律失常、神经内分泌系统疾病、压力、前列腺肥大和痉挛症。
• Antidepressant azaheterocyclymethyl derivatives of 2,3-dihydro-1,4-benzodioxan
  申请人：Wyeth

  公开号：US06559169B2

  公开（公告）日：2003-05-06

  Compounds of the formula useful for the treatment of depression and other conditions such as obsessive compulsive disorder, panic attacks, generalized anxiety disorder, sexual dysfunction, eating disorders, addictive disorders caused by ethanol or cocaine abuse and related illnesses.

  该式的化合物可用于治疗抑郁症和其他疾病，如强迫症、恐慌症、广泛性焦虑症、性功能障碍、进食障碍、由乙醇或可卡因滥用引起的成瘾性障碍及相关疾病。
• Antidepressant azaheterocyclylmethyl derivatives of 2,3-dihydro-1, 4-benzodiozan
  申请人：Wyeth

  公开号：US07041683B2

  公开（公告）日：2006-05-09

  Compounds of the formula useful for the treatment of depression and other conditions such as obsessive compulsive disorder, panic attacks, generalized anxiety disorder, sexual dysfunction, eating disorders, addictive disorders caused by ethanol or cocaine abuse and related illnesses.

  该式化合物可用于治疗抑郁症和其他疾病，如强迫症、惊恐障碍、广泛性焦虑障碍、性功能障碍、进食障碍、由乙醇或可卡因滥用引起的成瘾性障碍和相关疾病。
• HETEROCYCLYLCARBOXAMIDE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：ABBOTT GmbH & Co. KG

  公开号：EP0839145B1

  公开（公告）日：2003-11-05