3,4-二氢-7-甲氧基苯并[f][1,4]硫氮杂卓-5(2H)-酮 | 145903-32-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 中文名称: 3,4-二氢-7-甲氧基苯并[f][1,4]硫氮杂卓-5(2H)-酮
• 英文名称: 7-methoxy-3,4-dihydrobenzo[f][1,4]thiazepin-5(2H)-one
• 英文别名: 7-methoxy-3,4-dihydro-2H-1,4-benzothiazepin-5-one；7-methoxy-5-oxo-2,3,4,5-tetrahydro-1,4-benzothiazepine
• CAS: 145903-32-8
• 化学式: C₁₀H₁₁NO₂S
• 分子量: 209.269
• InChiKey: GYYTWZZEOQZZDK-UHFFFAOYSA-N

物化性质

• 沸点：
  475.7±45.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-二氢-7-甲氧基苯并[f][1,4]硫氮杂卓-5(2H)-酮 在 盐酸 、 lithium aluminium tetrahydride 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 0.5h， 生成 2,3,4,5-四氢-7-甲氧基-4-甲基-1,4-苯并硫氮杂卓
  参考文献：
  名称：

  Novel Carvedilol Analogues That Suppress Store-Overload-Induced Ca²⁺ Release

  摘要：

  Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part because of its ability to inhibit store-overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization, and bioassay of ca. 100 compounds based on the carvedilol motif to identify features that correlate with and optimize SOICR inhibition. A single-cell bioassay was employed on the basis of the RyR2-R4496C mutant HEK-293 cell line in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the beta-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits.

  DOI：

  10.1021/jm401090a
• 作为产物：
  描述：

  2-疏基-5-甲氧基苯甲酸 在 硫酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 19.0h， 生成 3,4-二氢-7-甲氧基苯并[f][1,4]硫氮杂卓-5(2H)-酮
  参考文献：
  名称：

  Ziresovir作为有效，选择性和口服生物可用的呼吸道合胞病毒融合蛋白抑制剂的发现。

  摘要：

  Ziresovir（RO-0529，AK0529）首次报道为有希望的呼吸道合胞病毒（RSV）融合（F）蛋白抑制剂，目前处于2期临床试验中。本文介绍了RO-0529作为有效，选择性和口服可生物利用的RSV F蛋白抑制剂的过程，并重点介绍了动物体内和体外的抗RSV活性和药代动力学。RO-0529在细胞分析中显示出对实验室菌株以及RSV临床分离株的个位数nM EC50效能，并且在RSV病毒感染的BALB / c小鼠模型中病毒载量减少了一个以上。通过鉴定RSV F蛋白中的D486N，D489V和D489Y的耐药突变以及在细胞分析中抑制RSV F蛋白诱导的细胞-细胞融合，证明RO-0529是一种特定的RSV F蛋白抑制剂。

  DOI：

  10.1021/acs.jmedchem.9b00654

文献信息

• Novel anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof
  申请人：Marks R. Andrew

  公开号：US20050215540A1

  公开（公告）日：2005-09-29

  The present invention provides methods for limiting or preventing a decrease in the level of RyR2-bound FKBP12.6 in a subject. The present invention further provides methods for treating and preventing atrial and ventricular cardiac arrhythmias, heart failure, and exercise-induced sudden cardiac death in a subject. Additionally, the present invention provides use of JTV-519 in a method for limiting or preventing a decrease in the level of RyR2-bound FKBP12.6 in a subject who has, or is a candidate for, atrial fibrillation. Also provided are uses of 1,4-benzothiazepine derivatives in methods for treating and preventing atrial and ventricular cardiac arrhythmias and heart failure in a subject, and for preventing exercise-induced sudden cardiac death. The present invention also provides methods for identifying agents for use in treating and preventing atrial fibrillation and heart failure, and agents identified by these methods.

  本发明提供了限制或预防受试者中RyR2结合FKBP12.6水平下降的方法。本发明进一步提供了治疗和预防受试者中心房和心室心律失常、心力衰竭以及运动诱发的突发性心脏死亡的方法。此外，本发明提供了在限制或预防受试者中RyR2结合FKBP12.6水平下降的方法中使用JTV-519的用途，该受试者患有或有可能患上心房颤动。还提供了1,4-苯并噻唑啉衍生物在治疗和预防受试者中心房和心室心律失常以及心力衰竭，以及预防运动诱发的突发性心脏死亡的方法中的用途。本发明还提供了用于识别用于治疗和预防心房颤动和心力衰竭的药剂的方法，以及通过这些方法识别的药剂。
• [EN] STORE OVERLOAD-INDUCED CALCIUM RELEASE INHIBITORS AND METHODS FOR PRODUCING AND USING THE SAME<br/>[FR] INHIBITEURS DE LIBÉRATION DU CALCIUM INDUITE PAR UNE SURCHARGE DU STOCK CALCIQUE ET LEURS MÉTHODES DE PRODUCTION ET D'UTILISATION
  申请人：UTI LIMITED PARTNERSHIP

  公开号：WO2015031914A1

  公开（公告）日：2015-03-05

  The present invention provides compounds having store overload-induced Ca2+ release (SOICR) inhibitory activity and methods for producing and using the same. In particular, compounds of the invention is of the formula: R1-X1-L-X2-R2, wherein R1, X1, L, X2, and R2 are those defined herein.

  本发明提供了具有存储过载诱导的Ca2+释放（SOICR）抑制活性的化合物以及生产和使用这些化合物的方法。特别是，本发明的化合物具有如下通式：R1-X1-L-X2-R2，其中R1、X1、L、X2和R2如本文所定义。
• NOVEL CALCIUM MODULATORS
  申请人：Myotherix, Inc.

  公开号：US20160207893A1

  公开（公告）日：2016-07-21

  Disclosed are novel calcium modulators having formula I: or a pharmaceutically acceptable salt, and including deuterated forms thereof, wherein: Z 1 , Z 2 , Z 3 , Z 4 Z 5 , R 1 , R 1′ , R 2 , R 3 , R 3′ R 4 , and R 4′ , are as defined throughout the specification; pharmaceutical compositions thereof; and methods of use thereof.

  公开了具有式I的新型钙调制剂：或其药学上可接受的盐，包括其氘代形式，其中：Z1、Z2、Z3、Z4、Z5、R1、R1′、R2、R3、R3′、R4和R4′，如说明书中所定义；其药物组合物；以及其使用方法。
• Novel agents for preventing and treating disorders involving modulation of the RyR receptors
  申请人：Marks R. Andrew

  公开号：US20070049572A1

  公开（公告）日：2007-03-01

  The present invention provides novel compounds of Formula I and salts, hydrates, solvates, complexes, and prodrugs thereof. The present invention further provides methods for synthesizing compounds of Formula I. The invention additionally provides pharmaceutical compositions comprising the compounds of Formula I and methods of using the pharmaceutical compositions of Formula I to treat and prevent disorders and diseases associated with the RyR receptors that regulate calcium channel functioning in cells. Such disorders and diseases include, by way of example only, cardiac disorders and diseases, skeletal muscular disorders and diseases, cognitive disorders and diseases, malignant hyperthermia, diabetes, and sudden infant death syndrome. Cardiac disorder and diseases include, but are not limited to, irregular heartbeat disorders and diseases; exercise-induced irregular heartbeat disorders and diseases; sudden cardiac death; exercise-induced sudden cardiac death; congestive heart failure; chronic obstructive pulmonary disease; and high blood pressure. Irregular heartbeat disorders and diseases include and exercise-induced irregular heartbeat disorders and diseases include, but are not limited to, atrial and ventricular arrhythmia; atrial and ventricular fibrillation; atrial and ventricular tachyarrhythmia; atrial and ventricular tachycardia; catecholaminergic polymorphic ventricular tachycardia (CPVT); and exercise-induced variants thereof. Skeletal muscular disorder and diseases include, but are not limited to, skeletal muscle fatigue, exercise-induced skeletal muscle fatigue, muscular dystrophy, bladder disorders, and incontinence. Cognitive disorders and diseases include, but are not limited to, Alzheimer's Disease, forms of memory loss, and age-dependent memory loss.

  本发明提供了Formula I的新化合物及其盐、水合物、溶剂合物、络合物和前药。本发明还提供了合成Formula I化合物的方法。此外，该发明还提供了包含Formula I化合物的药物组合物，以及使用Formula I药物组合物治疗和预防与调节细胞中钙通道功能的RyR受体相关的疾病和疾病的方法。这些疾病包括但不限于心脏疾病、骨骼肌肉疾病、认知障碍和疾病、恶性高热、糖尿病和婴儿猝死综合征。心脏疾病包括但不限于心律不齐疾病、运动诱发的心律不齐疾病、猝死、运动诱发的猝死、充血性心力衰竭、慢性阻塞性肺疾病和高血压。心律不齐疾病和疾病包括运动诱发的心律不齐疾病，但不限于心房和心室心律失常、心房和心室颤动、心房和心室快速心律失常、心房和心室快速心跳、儿茶酚胺多形性心室心动过速（CPVT）及其运动诱发的变体。骨骼肌肉疾病包括但不限于骨骼肌疲劳、运动诱发的骨骼肌疲劳、肌肉萎缩、膀胱疾病和失禁。认知障碍和疾病包括但不限于阿尔茨海默病、各种记忆丧失形式和年龄相关的记忆丧失。
• 1,4-benzothiazepine derivatives
  申请人：Kirin Brewery Co., Ltd.

  公开号：US05416066A1

  公开（公告）日：1995-05-16

  An object of the invention is to provide compounds having a myocardial KD (Kinetic cell death)-inhibiting effect without being accompanied by a cardiodepressant effect. A 1,4-benzothiazepine derivative represented by the following Formula [I]: ##STR1## wherein each of substituent groups is defined as follows: R represents H or a C.sub.1 -C.sub.3 lower alkoxy group; X represents O or H.sub.2 ; n represents 1 or 2; R.sup.1 represents H, a substituted phenyl group wherein the substituent group is OH or a C.sub.1 -C.sub.3 lower alkoxy group, ##STR2## a C.sub.1 -C.sub.3 lower alkoxy group, ##STR3## wherein R.sup.2 represents a C.sub.1 -C.sub.3 acyl group, and ph represents a phenyl group, or a pharmaceutically acceptable salt thereof.

  本发明的一个目的是提供具有心肌KD（动力细胞死亡）抑制作用的化合物，而不伴随心脏抑制作用。以下式[I]所代表的1,4-苯并噻吩衍生物：其中取代基的各个基团定义如下：R代表H或C.sub.1 -C.sub.3较低的烷氧基团；X代表O或H.sub.2；n代表1或2；R.sup.1代表H，一个取代的苯基团，其中取代基团为OH或C.sub.1 -C.sub.3较低的烷氧基团，##STR2##一个C.sub.1 -C.sub.3较低的烷氧基团，##STR3##其中R.sup.2代表一个C.sub.1 -C.sub.3酰基团，ph代表一个苯基团，或其药用盐。