7-溴-4甲基-3,4-二羟基-2H-1,4-苯并恶嗪 - CAS号 154264-95-6

物化性质

熔点：

47 °C
沸点：

309.2±42.0 °C(Predicted)
密度：

1.475

计算性质

辛醇/水分配系数(LogP)：

2.5
重原子数：

12
可旋转键数：

0
环数：

2.0
sp3杂化的碳原子比例：

0.33
拓扑面积：

12.5
氢给体数：

0
氢受体数：

2

安全信息

危险品标志：

Xi
安全说明：

S26,S37/39
危险类别码：

R36/37/38
海关编码：

2934999090
危险性防范说明：

P261,P305+P351+P338
危险性描述：

H315,H319,H335

SDS

SDS：679b21dd16a674b88e17a2b4d02cee73

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Name:	7-Bromo-4-methyl-3 4-dihydro-2h-1 4-benzoxazine tech Material Safety Data Sheet
Synonym:
CAS:	154264-95-6

Section 1 - Chemical Product MSDS Name:7-Bromo-4-methyl-3 4-dihydro-2h-1 4-benzoxazine tech Material Safety Data Sheet
Synonym:

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
154264-95-6	7-Bromo-4-methyl-3,4-dihydro-2H-1,4-be		unlisted

Hazard Symbols: XI
Risk Phrases: 36/37/38

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 154264-95-6: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: green
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C9H10BrNO
Molecular Weight: 228.09

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide, hydrogen bromide, bromine.
Hazardous Polymerization: Has not been reported

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 154264-95-6 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
7-Bromo-4-methyl-3,4-dihydro-2H-1,4-benzoxazine - Not listed by ACGIH, IARC, or NTP.

Section 12 - ECOLOGICAL INFORMATION

Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

Section 14 - TRANSPORT INFORMATION

IATA
No information available.
IMO
No information available.
RID/ADR
No information available.

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 154264-95-6: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 154264-95-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 154264-95-6 is not listed on the TSCA inventory.
It is for research and development use only.

SECTION 16 - ADDITIONAL INFORMATION
N/A

上下游信息

上游原料

中文名称英文名称 CAS号化学式分子量

4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪 4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine 77901-22-5 C₉H₁₁NO 149.192

中文名称	英文名称	CAS号	化学式	分子量
4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪	4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine	77901-22-5	C₉H₁₁NO	149.192

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	4,7-Dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine	141103-92-6	C₁₀H₁₃NO	163.219
4-甲基-3,4-二氢-2H-1,4-苯并噁嗪-7-甲醛	4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-carbaldehyde	141103-93-7	C₁₀H₁₁NO₂	177.203
——	2-ethylhexyl 3-[(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl)thio]propanoate	1156468-74-4	C₂₀H₃₁NO₃S	365.537

反应信息

作为反应物：

描述：

7-溴-4甲基-3,4-二羟基-2H-1,4-苯并恶嗪在 tris-(dibenzylideneacetone)dipalladium(0) 、 N-溴代丁二酰亚胺(NBS) 、三氟化硼乙醚、 sodium ethanolate 、 N,N-二异丙基乙胺、 4,5-双二苯基膦-9,9-二甲基氧杂蒽、三氟乙酸作用下，以四氢呋喃、 1,4-二氧六环、乙醇、二氯甲烷、乙腈为溶剂，反应 24.0h，生成 8-[(6-Bromo-4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)sulfanyl]-9-(2-piperidin-4-ylethyl)purin-6-amine

参考文献：

名称：

Discovery of (2S)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-hydroxypropan-1-one (MPC-3100), a Purine-Based Hsp90 Inhibitor

摘要：

Modulation of Hsp90 (heat shock protein 90) function has been recognized as an attractive approach for cancer treatment, since many cancer cells depend on Hsp90 to maintain cellular homeostasis. This has spurred the search for small-molecule Hsp90 inhibitors. Here we describe our lead optimization studies centered on the purine-based Hsp90 inhibitor 28a containing a piperidine moiety at the purine N9 position. In this study, key SAR was established for the piperidine N-substituent and for the congeners of the 1,3-benzodioxole at C8. These efforts led to the identification of orally bioavailable 28g that exhibits good in vitro profiles and a characteristic molecular biomarker signature of Hsp90 inhibition both in vitro and in vivo. Favorable pharmacokinetic properties along with significant antitumor effects in multiple human cancer xenograft models led to the selection of 28g (MPC-3100) as a clinical candidate.

DOI：

10.1021/jm3004619
作为产物：

描述：

2-甲氨基苯酚在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 作用下，以水、 N,N-二甲基甲酰胺、丙酮为溶剂，反应 72.0h，生成 7-溴-4甲基-3,4-二羟基-2H-1,4-苯并恶嗪

参考文献：

名称：

Synthesis and Reactions of 3,4-dihydro-2H-1,4-benzoxazine Derivatives

摘要：

Several 3,4-dihydro-2H-1,4-benzoxazine derivatives were prepared from commercially available benzoxazoles by use of an efficient two step sequence. Aryl functionalization reactions allowing access to further benzoxazine derivatives are also described.

DOI：

10.3987/com-93-6523

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文献信息

[EN] OGA INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'OGA

申请人：JANSSEN PHARMACEUTICA NV

公开号：WO2019243527A1

公开（公告）日：2019-12-26

The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations.

本发明涉及O-GlcNAc水解酶（OGA）抑制剂。该发明还涉及包含这类化合物的药物组合物，制备这类化合物和组合物的方法，以及利用这类化合物和组合物预防和治疗抑制OGA有益的疾病的用途，例如tau病变，特别是阿尔茨海默病或进行性核上性麻痹症；以及伴有tau病理的神经退行性疾病，特别是由C90RF72突变引起的肌萎缩侧索硬化或额颞叶痴呆症。
Novel Compounds for the Treatment of Diseases Associated with Amyloid or Amyloid-Like Proteins

申请人：Kroth Heiko

公开号：US20110280808A1

公开（公告）日：2011-11-17

The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

本发明涉及一种新型化合物，可用于治疗与淀粉样蛋白相关的一组疾病和异常，如阿尔茨海默病，以及与淀粉样蛋白类似蛋白相关的疾病或病况。本发明的化合物还可用于治疗与视觉系统组织中的病理异常/变化相关的眼部疾病。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物制备用于治疗或预防与淀粉样和/或淀粉样类似蛋白相关的疾病或病况的药物的用途。还公开了一种治疗或预防与淀粉样和/或淀粉样类似蛋白相关的疾病或病况的方法。
In Vivo Active Aldosterone Synthase Inhibitors with Improved Selectivity: Lead Optimization Providing a Series of Pyridine Substituted 3,4-Dihydro-1<i>H</i>-quinolin-2-one Derivatives

作者：Simon Lucas、Ralf Heim、Christina Ries、Katarzyna E. Schewe、Barbara Birk、Rolf W. Hartmann

DOI：10.1021/jm800888q

日期：2008.12.25

Pyridine substituted naphthalenes (e.g., I-III) constitute a class of potent inhibitors of aldosterone synthase (CYP11B2). To overcome the unwanted inhibition of the hepatic enzyme CYP1A2, we aimed at reducing the number of aromatic carbons of these molecules because aromaticity has previously been identified to correlate positively with CYP1A2 inhibition. As hypothesized, inhibitors with a tetrahydronaphthalene

吡啶取代的萘（例如，I-III）构成一类有效的醛固酮合酶（CYP11B2）抑制剂。为克服对肝酶CYP1A2的有害抑制作用，我们旨在减少这些分子的芳族碳原子数，因为先前已确定芳香性与CYP1A2抑制成正相关。如所假设的，具有四氢萘型分子支架的抑制剂（1-11）表现出降低的CYP1A2抑制作用。然而，四氢萘酮9在较高浓度下对人细胞系U-937具有细胞毒性。随之而来的结构优化最终发现了杂芳基取代的3,4-二氢-1H-喹啉-2-酮（12-26），其中12个生物立体异构体为9，在200 microM以下无毒。研究的分子对CYP1A2和多种其他细胞色素P450酶具有高度选择性，并且在体内具有良好的药代动力学特征（例如12种，口服生物利用度为71％）。此外，已证明异喹啉衍生物21可显着降低ACTH刺激大鼠的血浆醛固酮水平。
2-PYRIDONE COMPOUNDS

申请人：KAWAGUCHI Takanori

公开号：US20110237791A1

公开（公告）日：2011-09-29

A 2-pyridone compound represented by the formula [1]: wherein in the formula [1], the ring represented by A represents a benzene ring or a pyridine ring, X represents any of the structures represented by the formulas [3] shown below: V represents a single bond or a lower alkylene group, and W represents a single bond, an ether bond or a lower alkylene group (wherein the lower alkylene group may contain an ether bond)}, a tautomer or stereoisomer of the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is a compound that has an excellent GK activating effect and is useful as a pharmaceutical.

化学式为[1]所代表的2-吡啶酮化合物：其中在化学式[1]中，由A代表苯环或吡啶环表示的环， X代表下面所示的化学式[3]所代表的任意结构： V代表单键或较低的烷基链，以及 W代表单键、醚键或较低的烷基链（其中较低的烷基链可能含有醚键）}，该化合物的异构体或立体异构体，其药学上可接受的盐，或其溶剂化合物是一种具有出色的GK激活效果并且可用作药物的化合物。
[EN] NOVEL COMPOUNDS FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID OR AMYLOID-LIKE PROTEINS<br/>[FR] NOUVEAUX COMPOSÉS POUR LE TRAITEMENT DE MALADIES ASSOCIÉES AUX PROTÉINES AMYLOÏDES OU DE TYPE AMYLOÏDE

申请人：AC IMMUNE SA

公开号：WO2011128455A1

公开（公告）日：2011-10-20

The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

本发明涉及一类新化合物，可用于治疗与淀粉样蛋白相关的一组疾病和异常，例如阿尔茨海默病，以及与类淀粉样蛋白相关的疾病或状况。本发明的化合物还可用于治疗与视觉系统组织病理性异常/变化相关的眼病。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物制备用于治疗或预防与淀粉样和/或类淀粉样蛋白相关的疾病或状况的药物。还公开了一种治疗或预防与淀粉样和/或类淀粉样蛋白相关疾病或状况的方法。

7-溴-4甲基-3,4-二羟基-2H-1,4-苯并恶嗪 | 154264-95-6

分子结构分类

物化性质

计算性质

安全信息

SDS

上下游信息

反应信息

文献信息

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