(1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,6',19'-pentamethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-5-thia-7-azapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4(8),6,19-triene] | 1055989-15-5

分子结构分类

有机化合物 - 有机氮化合物

中文名称

——

中文别名

——

英文名称

(1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,6',19'-pentamethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-5-thia-7-azapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4(8),6,19-triene]

英文别名

——

(1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,6',19'-pentamethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-5-thia-7-azapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4(8),6,19-triene]化学式

CAS

1055989-15-5

化学式

C₃₀H₄₄N₂OS

mdl

——

分子量

480.758

InChiKey

XBQMRYPVKSIGMO-DZAOVQFVSA-N

BEILSTEIN

——

EINECS

——

物化性质

沸点：

600.4±55.0 °C(predicted)
密度：

1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

辛醇/水分配系数(LogP)：

6.1
重原子数：

34
可旋转键数：

0
环数：

7.0
sp3杂化的碳原子比例：

0.83
拓扑面积：

62.4
氢给体数：

1
氢受体数：

4

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
——	D-homocyclopamine	878204-97-8	C₂₈H₄₃NO₂	425.655
——	(3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3',6',11,12b-tetramethylspiro[2,4,4a,5,6,6a,6b,7,8,10,12,12a-dodecahydro-1H-naphtho[2,1-a]azulene-9,2'-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]-3-one	1037209-99-6	C₂₈H₄₃NO₂	425.655
——	IPI-269609	878204-96-7	C₂₈H₄₁NO₂	423.639
——	benzyl (2Z,3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-2-(hydroxymethylidene)-3',6',11,12b-tetramethyl-3-oxospiro[1,4,4a,5,6,6a,6b,7,8,10,12,12a-dodecahydronaphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate	1055981-18-4	C₃₇H₄₉NO₅	587.8
——	benzyl (3S,3'R,3'aS,6'S,6aS,6bS,7'aR,9S,12aS,12bR)-3',6',11,12b-tetramethyl-3-phenylmethoxycarbonyloxyspiro[1,2,3,4,6,6a,6b,7,8,10,12,12a-dodecahydronaphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate	1037210-11-9	C₄₄H₅₅NO₆	693.924
环巴胺	cyclopamine	4449-51-8	C₂₇H₄₁NO₂	411.628
——	benzyl (3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-3',6',11,12b-tetramethyl-3-oxospiro[2,4,4a,5,6,6a,6b,7,8,10,12,12a-dodecahydro-1H-naphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate	1037210-47-1	C₃₆H₄₉NO₄	559.789
——	benzyl (3'R,3'aS,4aR,6'S,6aR,6bS,7'aR,9S,12aS,12bS)-2-bromo-3',6',11,12b-tetramethyl-3-oxospiro[2,4,4a,5,6,6a,6b,7,8,10,12,12a-dodecahydro-1H-naphtho[2,1-a]azulene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-carboxylate	1055989-28-0	C₃₆H₄₈BrNO₄	638.685
——	BisCBzcyclopamine	1037210-08-4	C₄₃H₅₃NO₆	679.897

反应信息

作为产物：

描述：

环巴胺在 palladium(II) hydroxide/carbon 、 palladium 10% on activated carbon 吡啶、 4-二甲氨基吡啶、 N-溴代丁二酰亚胺(NBS) 、二(2,6-二甲基苯基)磷酸氢酯、 potassium tert-butylate 、氢气、 diethylzinc 、 sodium acetate 、 aluminum tri-tert-butoxide 、溶剂黄146 、三乙胺、丁酮作用下，以四氢呋喃、 1,4-二氧六环、吡啶、乙醇、二氯甲烷、水、乙酸乙酯、甲苯、叔丁醇为溶剂， -20.0~75.0 ℃ 、101.33 kPa 条件下，反应 95.25h，生成 (1'S,2S,2'S,3R,3aS,6S,7aR,10'R,13'R,14'S)-2',3,6,6',19'-pentamethylspiro[3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine-2,17'-5-thia-7-azapentacyclo[11.8.0.02,10.04,8.014,20]henicosa-4(8),6,19-triene]

参考文献：

名称：

WO2008/109184

摘要：

公开号：

点击查看最新优质反应信息

文献信息

HETEROCYCLIC CYCLOPAMINE ANALOGS AND METHODS OF USE THEREOF

申请人：Castro Alfredo C.

公开号：US20080293755A1

公开（公告）日：2008-11-27

The present invention relates to steroidal alkaloids that can be used in the treatment of hedgehog pathway related disorders, particularly cancer.

本发明涉及可用于治疗刺猬通路相关疾病，特别是癌症的类固醇生物碱。
Heterocyclic Cyclopamine Analogs and Methods of Use Thereof

申请人：Castro Alfredo C.

公开号：US20120065218A1

公开（公告）日：2012-03-15

The present invention relates to steroidal alkaloids that can be used in the treatment of hedgehog pathway related disorders, particularly cancer.

本发明涉及类固醇生物碱，可用于治疗刺猬通路相关疾病，特别是癌症。
Discovery of a Potent and Orally Active Hedgehog Pathway Antagonist (IPI-926)

作者：Martin R. Tremblay、André Lescarbeau、Michael J. Grogan、Eddy Tan、Grace Lin、Brian C. Austad、Lin-Chen Yu、Mark L. Behnke、Somarajan J. Nair、Margit Hagel、Kerry White、James Conley、Joseph D. Manna、Teresa M. Alvarez-Diez、Jennifer Hoyt、Caroline N. Woodward、Jens R. Sydor、Melissa Pink、John MacDougall、Matthew J. Campbell、Jill Cushing、Jeanne Ferguson、Michael S. Curtis、Karen McGovern、Margaret A. Read、Vito J. Palombella、Julian Adams、Alfredo C. Castro

DOI：10.1021/jm900305z

日期：2009.7.23

Recent evidence suggests that blocking aberrant hedgehog pathway signaling may be a promising therapeutic strategy for the treatment of several types of cancer. Cyclopamine, a plant Veratrum alkaloid, is a natural product antagonist of the hedgehog pathway. In a previous report, a seven-membered D-ring semisynthetic analogue of cyclopamine, IPI-269609 (2), was shown to have greater acid stability and better aqueous solubility compared to cyclopamine. Further modifications of the A-ring system generated three series of analogues with improved potency and/or Solubility. Lead compounds from each series were characterized in vitro and evaluated in vivo for biological activity and pharmacokinetic properties. These studies led to the discovery of IPI-926 (compound 28), a novel semisynthetic cyclopamine analogue with substantially improved pharmaceutical properties and potency and a favorable pharmacokinetic profile relative to cyclopamine and compound 2. As a result, complete tumor regression was observed in a Hh-dependent medulloblastoma allograft model after daily oral administration of 40 mg/kg of compound 28.
TREATMENT OF FIBROTIC CONDITIONS USING HEDGEHOG INHIBITORS

申请人：Levine Arnold J.

公开号：US20110183948A1

公开（公告）日：2011-07-28

Provided is a method of treating a fibrotic condition with a hedgehog inhibitor.
THERAPEUTIC REGIMENS FOR HEDGEHOG-ASSOCIATED CANCERS

申请人：MacDougall John R.

公开号：US20120010229A1

公开（公告）日：2012-01-12

Provided herein are methods, therapeutic regimens, and kits that optimize the benefits of hedgehog inhibition for cancer therapy.