波来瑞斯 - CAS号 72702-95-5

物化性质

熔点：

184-186℃ (DEC.)
密度：

1.60
溶解度：

DMF：2 mg/ml；二甲基亚砜：2 mg/ml；乙醇：2 mg/ml； PBS（pH 7.2）：0.2 mg/ml

计算性质

辛醇/水分配系数(LogP)：

3.2
重原子数：

24
可旋转键数：

4
环数：

3.0
sp3杂化的碳原子比例：

0.12
拓扑面积：

70
氢给体数：

1
氢受体数：

5

安全信息

危险类别码：

R36/37/38
海关编码：

2933990090
安全说明：

S26,S36/37/39
危险性防范说明：

P261,P305+P351+P338
危险性描述：

H302,H315,H319,H335
储存条件：

-20°C

SDS

SDS：a69ffa9de6d733a4250a88a12eb8934e

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制备方法与用途

概述

波来瑞斯可用作医药合成中间体。若吸入波来瑞斯，应将患者移至新鲜空气处；如皮肤接触，需脱去污染衣物，并用肥皂水和清水彻底冲洗皮肤；如有不适，请就医；如眼睛接触到物质，应分开眼睑并用流动清水或生理盐水冲洗，随后立即就医；若误食，则应立即漱口，禁止催吐，并尽快寻求医疗帮助。

生物活性

Ponalrestat（ICI 128436）是一种具有口服活性、选择性和非竞争性的醛糖还原酶抑制剂。它能够特异性地抑制ALR2，Ki值为7.7 nM；对ALR1的Ki值为60 μM。Ponalrestat可以抑制葡萄糖向山梨糖醇的转化。

靶点

Ki: 7.7 nM (ALR2) and 60 μM (ALR1)

体外研究

在内膜细胞和内膜组织切片中，Ponalrestat（ICI 128436；1, 10, 100 μM；6小时）能减少由IL-1刺激产生的PGF2α的产生。

体内研究

Ponalrestat（ICI 128436；10, 50 mg/kg；口服；每日一次；8周）减少了山梨糖醇的积累，表明醛糖还原酶抑制效果良好。实验结果显示：

动物模型：成年雌性Sprague-Dawley大鼠
剂量：10, 50 mg/kg
给药方式：口服，每日一次，8周
结果：山梨糖醇积累减少

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
2-(4-氧-3,4-二氢邻苯二甲秦)乙酸	2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid	25947-11-9	C₁₀H₈N₂O₃	204.185
(4-氧代-3,4-二氢二氮杂萘-1-基)-乙酸乙酯	ethyl 2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetate	25947-13-1	C₁₂H₁₂N₂O₃	232.239

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	2-(4-bromo-2-fluorobenzyl)-4-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)phthalazin-1(2H)-one	1226760-14-0	C₂₂H₂₂BrFN₄O₂	473.345
——	2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-phenylacetamide	1226760-00-4	C₂₃H₁₇BrFN₃O₂	466.309
——	2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(4-bromophenyl)acetamide	1226760-03-7	C₂₃H₁₆Br₂FN₃O₂	545.205
——	2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(4-fluorophenyl)acetamide	1226760-01-5	C₂₃H₁₆BrF₂N₃O₂	484.3
——	2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(4-chlorophenyl)acetamide	1226760-02-6	C₂₃H₁₆BrClFN₃O₂	500.754
——	2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxophthalazin-4-yl)-N-(pyridin-2-yl)acetamide	1226760-10-6	C₂₂H₁₆BrFN₄O₂	467.297
——	2-(4-bromo-2-fluorobenzyl)-4-(2-(4-benzylpiperazin-1-yl)-2-oxoethyl)phthalazin-1(2H)-one	1226760-21-9	C₂₈H₂₆BrFN₄O₂	549.442
——	2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(4-bromo-5-methylphenyl)acetamide	1226760-07-1	C₂₄H₁₈Br₂FN₃O₂	559.232
——	2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(2,6-dimethylphenyl)acetamide	1226760-09-3	C₂₅H₂₁BrFN₃O₂	494.363
——	2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(2,4-dimethylphenyl)acetamide	1226760-08-2	C₂₅H₂₁BrFN₃O₂	494.363

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反应信息

作为反应物：

描述：

2-氨基-5-硝基噻唑、波来瑞斯在 N,N'-二环己基碳二亚胺作用下，以二氯甲烷为溶剂，反应 0.5h，以44%的产率得到2-(2-(4-bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo-phthalazin-4-yl)-N-(5-nitrothiazol-2-yl)acetamide

参考文献：

名称：

Synthesis and Antimycobacterial Evaluation of Novel Phthalazin-4-ylacetamides Against log- and Starved Phase Cultures

摘要：

Twenty four novel 2‐[3‐(4‐bromo‐2‐fluorobenzyl)‐4‐oxo‐3,4‐dihydro‐1‐phthalazinyl]acetic acid amides were synthesized from phthalic anhydride and were subjected to in vitro and in vivo evaluation against log‐ and starved phase of mycobacterial species and Mycobacterium tuberculosis isocitrate lyase enzyme inhibition studies. Among the compounds screened, 2‐(2‐(4‐bromo‐2‐fluorobenzyl)‐1,2‐dihydro‐1‐oxophthalazin‐4‐yl)‐N‐(2,6‐dimethylphenyl)acetamide (5j) inhibited all eight mycobacterial species with MIC’s ranging from 0.08 to 5.05 μm and was non‐toxic to Vero cells till 126.43 μm. Four compounds were tested against starved culture of Mycobacterium tuberculosis and they inhibited with MIC’s ranging from 3.78 to 23.2 μm. Some compounds showed 40–66% inhibition against Mycobacterium tuberculosis isocitrate lyase enzyme at 10 μm. The docking studies also confirmed the binding potential of the compounds at the isocitrate lyase active site. In the in vivo animal model, 5j reduced the mycobacterial load in lung and spleen tissues with 1.38 and 2.9‐log10 protections, respectively, at 25 mg/kg body weight dose.

DOI：

10.1111/j.1747-0285.2010.00947.x
作为产物：

描述：

4-溴-2-氟苄溴、 (4-氧代-3,4-二氢二氮杂萘-1-基)-乙酸乙酯在 4-溴-2-氟苄溴作用下，以54的产率得到波来瑞斯

参考文献：

名称：

Phthalazin-4-ylacetic acid derivatives

摘要：

本发明涉及一种酶抑制剂，即一种通式I的新型邻苯二氮芦啉-4-乙酸衍生物：##STR1##以及适当的药物可接受盐，其制药组合物和类似物的制造方法。式I的化合物是体内醛糖还原酶的抑制剂，因此可能有助于减少或预防外周效应的发展，如黄斑水肿、白内障、视网膜病变或神经传导障碍。首选化合物为2-(2-氟-4-溴苯基)-1,2-二氢-1-氧杂苯并[4,5-f]吡嗪-4-乙酸。

公开号：

US04251528A1

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文献信息

[EN] ALKYNYL ARYL CARBOXAMIDES<br/>[FR] ALKYNYLARYL-CARBOXAMIDES

申请人：APPLIED RESEARCH SYSTEMS

公开号：WO2005012280A1

公开（公告）日：2005-02-10

The present invention is related to alkynyl aryl carboxamides of Formula (I’) and use thereof for the treatment and/or prevention of an inflammatory disorder, obesity and/or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and/or II, inadequate glucose tolerance. insulin resistance, hyperlipidemia, hypertriglyceridemia- hypercholesterolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of alkynyl aryl carboxamides of Formula (I’) to modulate, notably to inhibit the activity of PTPs. (I’) A is a C2-C15 alkynyl, C2-C6-alkynyl aryl, C2-C6-alkynyl heteroaryl. Cy is an aryl, heteroaryl, cycloalkyl or heterocycle group; n is either 0 or 1. Cy' is an aryl., which may optionally be fused by a 3-8 membered cycloalkyl. R1and R2 are independently from each other is selected from the group consisting of hydrogen or (CI-C6)alkyl. R4and R5 are each independently from each other selected from the group consisting of H, hydroxy. C1 -C6 alkyl, carboxy, C1-C6 alkoxy, C1 -C3 alkyl carboxy, C2-C3 alkenyl carboxy, C2-C3 alkynyl carboxy, amino or R4 and R5 may form an unsaturated or saturated heterocyclic ring, whereby at least one of R4 or R5 is not a hydrogen or C1-C6 alkyl.

本发明涉及式(I')的炔基芳基羧酰胺及其用于治疗和/或预防由胰岛素抵抗或高血糖介导的炎症疾病、肥胖和/或代谢紊乱的使用，包括I型和/或II型糖尿病、葡萄糖耐量不足、胰岛素抵抗、高脂血症、高甘油三酯血症-高胆固醇血症、多囊卵巢综合征(PCOS)。特别是，本发明涉及使用式(I')的炔基芳基羧酰胺来调节，尤其是抑制PTPs的活性。(I') A是C2-C15炔基，C2-C6-炔基芳基，C2-C6-炔基杂芳基。Cy是芳基、杂芳基、环烷基或杂环族；n是0或1。Cy'是一个芳基，它可以选择性地通过一个3-8成员的环烷基融合。R1和R2独立地互选自由氢或(C1-C6)烷基组成的组。R4和R5各自独立地互选自H、羟基。C1-C6烷基、羧基、C1-C6烷氧基、C1-C3烷基羧基、C2-C3烯基羧基、C2-C3炔基羧基、氨基或R4和R5可以形成一个不饱和或饱和的杂环，其中至少R4或R5不是氢或C1-C6烷基。
BICYCLIC COMPOUNDS AND USE AS ANTIDIABETICS

申请人：Fang Jing

公开号：US20100029650A1

公开（公告）日：2010-02-04

The present invention relates to novel compounds that are useful in the treatment of metabolic disorders, particularly type II diabetes mellitus and related disorders, and also to the methods for the making and use of such compounds.

本发明涉及一种新型化合物，该化合物在治疗代谢性疾病，特别是Ⅱ型糖尿病及相关疾病方面具有用途，并且还涉及制备和使用这种化合物的方法。
[EN] BENZYLBENZENE DERIVATIVES AND METHODS OF USE<br/>[FR] DÉRIVÉS DE BENZYLBENZÈNE ET PROCÉDÉS D'UTILISATION

申请人：THERACOS INC

公开号：WO2009026537A1

公开（公告）日：2009-02-26

Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT inhibition.

提供了对钠依赖性葡萄糖共转运蛋白SGLT具有抑制作用的化合物。该发明还提供了制药组合物、制备这些化合物的方法、合成中间体以及使用这些化合物的方法，独立地或与其他治疗剂联合使用，用于治疗受SGLT抑制影响的疾病和症状。
[EN] 1,1'-(1,2-ETHYNEDIYL)BIS-BENZENE DERIVATIVES AS PTP 1-B INHIBITORS<br/>[FR] DERIVES DE 1,1'-(1,2-ETHYNEDIYLE)BIS-BENZENE INHIBITEURS DE PTP 1-B

申请人：APPLIED RESEARCH SYSTEMS

公开号：WO2005097773A1

公开（公告）日：2005-10-20

The present invention is related to carboxylic acids of Formula (I) and use thereof for the treatment and/or prevention of obesity and/or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and/or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of carboxylic acids of Formula (I) to modulate, notably to inhibit the activity of PTPs.

本发明涉及式(I)的羧酸及其用于治疗和/或预防肥胖和/或由胰岛素抵抗或高血糖介导的代谢紊乱的使用，包括I型和/或II型糖尿病、葡萄糖耐量不足、胰岛素抵抗、高脂血症、高甘油三酯血症、高胆固醇血症、多囊卵巢综合征（PCOS）。特别是，本发明涉及使用式(I)的羧酸来调节，尤其是抑制PTPs的活性。
[EN] ARYL DICARBOXAMIDES<br/>[FR] ARYL-DICARBOXAMIDES

申请人：APPLIED RESEARCH SYSTEMS

公开号：WO2005011685A1

公开（公告）日：2005-02-10

The present invention is related to aryl dicarboxamides of formula (I) and use thereof for the treatment and/or prevention of obesity and/or metabolic disorders mediated by insulin resistance or hyperglycernia, comprising diabetes type I and/or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholes-terolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of aryl dicarboxamides of formula (I) to modulate, notably to inhibit the activity of PTPs. A is an airninocarbonyl moiety; Cy is an aryl, heteroaryl, aryl-heteroaryl, heteroaryl-aryl, aryl-aryl, cycloalkyl or heterocycle group; n is either 0 or 1; R1 and R2 are independently from each other is selected from the group consisting of hydrogen or C1-C6-alkyl; R4 and R5 are each independently from each other selected from the group consisting of H, hydroxy, C1-C6 alkyl, carboxy, C1-C6 alkoxy, C1-C3 alkyl carboxy, C2-C3 alkenyl carboxy, C2-C3 alkynyl carboxy, amino or R4 and R5 may form an unsaturated or saturated heterocyclic ring, whereby at least one of R4 or R5 is not a hydrogen or C1-C6 alkyl.

本发明涉及式(I)的芳基二羧酰胺及其用于治疗和/或预防肥胖和/或由胰岛素抵抗或高血糖介导的代谢紊乱的使用，包括I型和/或II型糖尿病、葡萄糖耐量不足、胰岛素抵抗、高脂血症、高甘油三酯血症、高胆固醇血症、多囊卵巢综合征(PCOS)。特别是，本发明涉及使用式(I)的芳基二羧酰胺调节，尤其是抑制PTPs的活性。A是氨基甲酰基团；Cy是芳基、杂芳基、芳基-杂芳基、杂芳基-芳基、芳基-芳基、环烷基或杂环组；n为0或1；R1和R2独立地选自由氢或C1-C6-烷基组成的组；R4和R5各自独立地选自由H、羟基、C1-C6烷基、羧基、C1-C6烷氧基、C1-C3烷基羧基、C2-C3烯基羧基、C2-C3炔基羧基、氨基组成的组，或者R4和R5可以形成一个不饱和或饱和的杂环，其中至少R4或R5不是氢或C1-C6烷基。

波来瑞斯 | 72702-95-5

物质功能分类

分子结构分类

物化性质

计算性质

安全信息

SDS

制备方法与用途

上下游信息

反应信息

文献信息

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