1H-6-bromo-4-isopropyl-1,3-dimethylpyrazolo[3,4-b]pyridine | 383858-39-7

分子结构分类

有机化合物 - 有机杂环化合物 - 吡唑并吡啶类

中文名称

——

中文别名

——

英文名称

1H-6-bromo-4-isopropyl-1,3-dimethylpyrazolo[3,4-b]pyridine

英文别名

6-bromo-4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine；6-Bromo-1,3-dimethyl-4-propan-2-ylpyrazolo[3,4-b]pyridine

1H-6-bromo-4-isopropyl-1,3-dimethylpyrazolo[3,4-b]pyridine化学式

CAS

383858-39-7

化学式

C₁₁H₁₄BrN₃

mdl

——

分子量

268.156

InChiKey

AKBNUNWKRWIUTM-UHFFFAOYSA-N

BEILSTEIN

——

EINECS

——

物化性质

沸点：

361.0±37.0 °C(Predicted)
密度：

1.47±0.1 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

3.4
重原子数：

15
可旋转键数：

1
环数：

2.0
sp3杂化的碳原子比例：

0.45
拓扑面积：

30.7
氢给体数：

0
氢受体数：

2

上下游信息

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6-carbonitrile	1352830-71-7	C₁₂H₁₄N₄	214.27
——	4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-ylamine	1352830-48-8	C₁₁H₁₆N₄	204.275
——	6-hydrazinyl-4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine	383858-40-0	C₁₁H₁₇N₅	219.289
——	(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-(methyl)amine	1352830-54-6	C₁₂H₁₈N₄	218.302
——	N-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N'-methyl-hydrazine	1352830-51-3	C₁₂H₁₉N₅	233.316
——	4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6-carboxamide	1352830-72-8	C₁₂H₁₆N₄O	232.285
——	N-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N-methyl-hydrazine	1352830-50-2	C₁₂H₁₉N₅	233.316
——	N-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N,N'-dimethylhydrazine	1352830-55-7	C₁₃H₂₁N₅	247.343
——	N-(2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-ylamino)-acetamide	1352829-92-5	C₁₈H₂₀Cl₂N₆O	407.302
——	dibenzyl-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-amine	1352830-47-7	C₂₅H₂₈N₄	384.524
——	N-(2-chloroethyl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-2-methylhydrazinecarboxamide	1352830-52-4	C₁₅H₂₃ClN₆O	338.84
——	N-(2-chloro-6-fluoropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide	1352830-13-7	C₁₇H₁₉ClFN₇O	391.836
——	N-(2-chloro-6-iodopyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide	1352830-14-8	C₁₇H₁₉ClIN₇O	499.742
——	N-(2-chloro-6-iodopyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)diazene-1-carboxamide	1352830-15-9	C₁₇H₁₇ClIN₇O	497.726
——	N-(2,6-dichloropyridin-4-ylcarbamoyl)-4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6-carboxamide	1352830-11-5	C₁₈H₁₈Cl₂N₆O₂	421.286
——	N-(2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-2-methylhydrazinecarboxamide	1352829-93-6	C₁₈H₂₁Cl₂N₇O	422.317
——	N-(2-chloro-6-(trimethylstannyl)pyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide	1352830-16-0	C₂₀H₂₈ClN₇OSn	536.652
——	1-[(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-methyl-amino]-imidazolidin-2-one	1352830-53-5	C₁₅H₂₂N₆O	302.379
——	N-(2-chloro-6-iodopyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-2-methylhydrazinecarboxamide	1352830-01-3	C₁₈H₂₁ClIN₇O	513.769
——	N-(2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-1,2-dimethylhydrazinecarboxamide	1352829-98-1	C₁₉H₂₃Cl₂N₇O	436.344
——	N3-(2,6-dichloropyridin-4-yl)-1-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-1H-1,2,4-triazole-3,5-diamine	1352830-12-6	C₁₈H₁₉Cl₂N₉	432.315
——	4,6-dichloro-N'-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-N'-methyl-1H-pyrrolo[3,2-c]pyridine-2-carbohydrazide	1352830-03-5	C₂₀H₂₁Cl₂N₇O	446.339
——	1-(2,6-dichloro-pyridin-4-yl)-3-[(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-methyl-amino]-imidazolidin-2-one	1352829-95-8	C₂₀H₂₃Cl₂N₇O	448.355
——	1-(4,6-dichloro-pyridin-2-yl)-3-[(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-methyl-amino]-imidazolidin-2-one	1352829-96-9	C₂₀H₂₃Cl₂N₇O	448.355

反应信息

作为反应物：

描述：

1H-6-bromo-4-isopropyl-1,3-dimethylpyrazolo[3,4-b]pyridine 在肼作用下，以四氢呋喃、乙醇、甲苯为溶剂，生成 N-(2-chloro-6-(2-methoxyethoxy)pyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide

参考文献：

名称：

A potent and selective C-11 labeled PET tracer for imaging sphingosine-1-phosphate receptor 2 in the CNS demonstrates sexually dimorphic expression

摘要：

Sphingosine-1-phosphate receptor 2（S1PR2）在调节脱髓鞘中枢神经系统（CNS）疾病期间的血脑屏障（BBB）功能中起着至关重要的作用。

DOI：

10.1039/c5ob00951k
作为产物：

描述：

异丁酰乙酸乙酯在溶剂黄146 、苯甲醚、三溴氧磷作用下，反应 27.0h，生成 1H-6-bromo-4-isopropyl-1,3-dimethylpyrazolo[3,4-b]pyridine

参考文献：

名称：

吡唑并吡啶衍生物作为鞘氨醇1-磷酸受体2配体的设计与合成

摘要：

通过修饰先导化合物N- (2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1 H - pyrazolo[ 3,4- b ]pyridin-6-yl)hydrazine-1-carboxamide (JTE-013) 及其对 S1PRs 的结合亲和力在体外使用 [ 32 P]S1P 和表达重组人 S1PRs 的细胞膜进行测定。在这些配体中，35a (IC 50  = 29.1 ± 2.6 nM) 和35b (IC 50  = 56.5 ± 4.0 nM) 对 S1PR2 的结合效力与 JTE-013 (IC 50  = 58.4 ± 7.4 nM) 相当，对 S1PR2 具有良好的选择性其他 S1PR （IC50  > 1000 纳米）。这些类似物的进一步优化可能会识别出针对 S1PR2 的其他更有效和选择性的化合物。

DOI：

10.1016/j.bmcl.2017.12.010

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文献信息

[EN] JTE013 ANALOGS AND METHODS OF MAKING AND USING SAME<br/>[FR] ANALOGUES DE JTE013 ET LEURS PROCÉDÉS DE PRÉPARATION ET D'UTILISATION

申请人：BRACCO IMAGING SPA

公开号：WO2011159864A1

公开（公告）日：2011-12-22

JTE013 analogs having similar or greater stability relative to JTE013 are provided. Also provided are JTE013 analogs which can bind to both S1P2 and S IP5, some of which also have similar or greater stability relative to JTE013. In addition, methods for the treatment and prevention of diseases and conditions associated with S1P2 and S IP5 receptors are provided.

提供了与JTE013具有类似或更高稳定性的JTE013类似物。还提供了可以结合到S1P2和S IP5的JTE013类似物，其中一些相对于JTE013也具有类似或更高的稳定性。此外，还提供了与S1P2和S IP5受体相关的疾病和病况的治疗和预防方法。
[EN] NOVEL SPHINGOSINE 1-PHOSPHATE RECEPTOR ANTAGONISTS<br/>[FR] NOUVEAUX ANTAGONISTES DE RÉCEPTEUR DE SPHINGOSINE 1-PHOSPHATE

申请人：SWENSON ROLF ERIC

公开号：WO2014158302A1

公开（公告）日：2014-10-02

The present invention relates to sphingosine-1 -phosphate (S1 P) receptors and compounds of the general formula (1), that are useful in the treatment and prevention of conditions associated with such receptors. More specifically, the present invention relates to the synthesis and use of sphingosine 1 -phosphate receptor 2 (S1 P2) antagonists that are useful in the treatment of cancer, atherosclerosis, diabetic retinopathy, and other inflammatory diseases. Among these inflammatory diseases that could be treated with these S1 P2 antagonist are those characterized by fibrosis including chronic lung disease, chronic kidney and liver disease, chronic heart disease, and skin diseases such as sclerosis/scleroderma. The S1 P2 antagonists can also be used in the treatment of glioblastoma multiforme (brain cancer), pediatric neuroblastoma, and other cancers.

本发明涉及鞘氨醇-1-磷酸（S1P）受体和一般式（1）的化合物，这些化合物在与这些受体相关的疾病的治疗和预防中是有用的。更具体地，本发明涉及合成和使用鞘氨醇-1-磷酸受体2（S1P2）拮抗剂，这些拮抗剂在癌症、动脉粥样硬化、糖尿病视网膜病变和其他炎症性疾病的治疗中是有用的。这些炎症性疾病中可以用这些S1P2拮抗剂治疗的包括以纤维化为特征的疾病，如慢性肺病、慢性肾脏和肝脏疾病、慢性心脏病，以及硬化/硬皮病等皮肤病。S1P2拮抗剂还可用于治疗多形性胶质母细胞瘤（脑癌）、儿童神经母细胞瘤和其他癌症。
新規なスフィンゴシン１‐リン酸受容体アンタゴニスト

申请人：スウェンソン，ロルフ，イー

公开号：JP2015524789A

公开（公告）日：2015-08-27

本発明は、式（Ｉ）のスフィンゴシン‐１‐リン酸受容体２（Ｓ１Ｐ２）アンタゴニストを含み、式中、Ｒ１は、−ＣＨ２ＣＨ＝ＣＨ２、−ＣＨ３、または−ＣＨ２ＣＨ２ＣＨ２ＯＨであり、Ｒ２は、−Ｈ、−ＣＨ２ＣＯ２Ｈ、−ＣＨ２ＣＨ２ＯＨ、−ＣＨ２ＣＨ２ＣＨ２ＯＨ、−ＣＨ２ＣＯＮＨ２、または−ＣＨ２ＣＯ２Ｅｔであり、Ｒ３は、４‐置換‐２，６‐ジクロロピリジン、４‐置換２‐クロロ‐６‐ヒドロキシエチルピリジン、４‐置換‐２‐クロロ‐６‐ヒドロキシプロピルピリジン、４‐置換‐２‐（アミノエチル）‐６‐クロロピリジン、４‐置換‐２‐（アミノエチルメチル）‐６‐クロロピリジン、または５‐置換‐２，３‐ジクロロチオフェンである。スフィンゴシン‐１‐リン酸Ｓ１Ｐ２受容体２アンタゴニスト受容体を含む医薬組成物も、腫瘍性眼障害および失明、ならびに線維性肺、腎臓、肝臓、および皮膚疾患の治療に有用であるとして開示される。【選択図】なし

This invention includes a sphingosine-1-phosphate receptor 2 (S1P2) antagonist of formula (I), wherein R1 is -CH2CH=CH2, -CH3, or -CH2CH2CH2OH, R2 is -H, -CH2CO2H, -CH2CH2OH, -CH2CH2CH2OH, -CH2CONH2, or -CH2CO2Et, and R3 is 4-substituted-2,6-dichloropyridine, 4-substituted-2-chloro-6-hydroxyethylpyridine, 4-substituted-2-chloro-6-hydroxypropylpyridine, 4-substituted-2-(aminoethyl)-6-chloropyridine, 4-substituted-2-(aminoethylmethyl)-6-chloropyridine, or 5-substituted-2,3-dichlorothiophene. It is disclosed that a pharmaceutical composition containing a sphingosine-1-phosphate S1P2 receptor antagonist receptor is useful in the treatment of ocular tumors and blindness, as well as fibrotic lung, kidney, liver, and skin diseases.【No selection figure】
Novel Sphingosine 1-Phosphate Receptor Antagonists

申请人：SWENSON Rolf E.

公开号：US20150045332A1

公开（公告）日：2015-02-12

The present invention relates to sphingosine-1-phosphate (S1P) receptors and compounds of the general formula: that are useful in the treatment and prevention of conditions associated with such receptors. More specifically, the present invention relates to the synthesis and use of sphingosine 1-phosphate receptor 2 (S1P 2 ) antagonists that are useful in the treatment of cancer, atherosclerosis, diabetic retinopathy, and other inflammatory diseases. Among these inflammatory diseases that could be treated with these S1P 2 antagonist are those characterized by fibrosis including chronic lung disease, chronic kidney and liver disease, chronic heart disease, and skin diseases such as sclerosis/scleroderma. The S1P 2 antagonists can also be used in the treatment of glioblastoma multiforme (brain cancer), pediatric neuroblastoma, and other cancers.

本发明涉及鞘氨醇-1-磷酸（S1P）受体和下列通式的化合物：这些化合物在治疗和预防与此类受体相关的疾病方面是有用的。更具体地，本发明涉及合成和使用鞘氨醇1-磷酸受体2（S1P2）拮抗剂，这些拮抗剂在治疗癌症、动脉硬化、糖尿病视网膜病变和其他炎症性疾病方面是有用的。这些炎症性疾病中，可以用这些S1P2拮抗剂治疗那些以纤维化为特征的疾病，包括慢性肺病、慢性肾脏和肝脏疾病、慢性心脏病以及硬化/硬皮病等皮肤疾病。S1P2拮抗剂还可以用于治疗多形性胶质母细胞瘤（脑癌）、儿童神经母细胞瘤和其他癌症。
NOVEL SPHINGOSINE 1-PHOSPHATE RECEPTOR ANTAGONISTS

申请人：Arroyo BioSciences L.L.C.

公开号：EP2831072B1

公开（公告）日：2017-04-19