Substituted isoquinoline derivative

A technology of isoquinoline and derivatives, applied in the field of isoquinoline-6-sulfonamide derivatives, to achieve excellent effect of lowering intraocular pressure

Active Publication Date: 2012-05-09
株式会社D.西医疗法研究所
View PDF7 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few reports on compounds in which the 6-position of the isoquinoline skeleton is substituted by an aminosulfonyl group. The cannabinoid receptor antagonist disclosed in Patent Document 1, the mitochondrial F1FOATPase inhibitor disclosed in Patent Document 2, and the The disclosed methods for the manufacture of compounds with phenoxy groups are equivalent to those reported

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Substituted isoquinoline derivative
  • Substituted isoquinoline derivative
  • Substituted isoquinoline derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0172] Production examples of synthetic intermediates and compounds of the present invention, and evaluation examples of biological activity are shown below. It should be noted that these illustrations are for better understanding of the present invention and do not limit the scope of the present invention. In addition, unless otherwise specified, Boc in the chemical structural formula represents a tert-butoxycarbonyl group.

reference example 1

[0175] Synthesis of 6-aminoisoquinoline (reference compound 1)

[0176]

[0177]17.2 g of 6-bromoisoquinoline (refer to WO 2008 / 077553) was weighed in an autoclave, 200 mL of 28% ammonia water and 10.8 g of copper sulfate pentahydrate were added and sealed, and stirred at 190 degrees for 6 hours. After cooling to room temperature, the reaction solution was poured into 250 mL of 10% aqueous sodium hydroxide solution, and extracted with ethyl acetate (100 mL×5). The extract was dried over anhydrous sodium sulfate, filtered, and then concentrated. The obtained crude product was suspended with dichloromethane, and filtered off to obtain 10.2 g (85%) of the target product as light brown crystals.

[0178] 1 H-NMR spectrum (CDCl 3 , δppm): 5.54(br s, 2H), 6.58(s, 1H), 7.00(d, J=9.0Hz, 1H), 7.35(d, J=5.5Hz, 1H), 7.75(d, J=9.0 Hz, 1H), 8.32(d, J=5.5Hz, 1H), 8.98(s, 1H)

reference example 2

[0180] Synthesis of 6-chlorosulfonylisoquinoline (reference compound 2)

[0181]

[0182] Suspend 4.0 g of 6-aminoisoquinoline (reference compound 1) in 40 mL of concentrated hydrochloric acid (35%) at 0°C, add 4.0 g of sodium nitrite little by little, and stir for 30 minutes. This reaction solution was dropped into a mixed solution of 20 mL of acetic acid saturated with sulfur dioxide gas generated from sodium bisulfite and sulfuric acid and 298 mg of copper chloride at 0° C., and stirred for 1 hour. It was neutralized by adding saturated aqueous sodium bicarbonate solution, and extracted with dichloromethane (100 mL×2). The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. Since the target product was unstable, the obtained dichloromethane solution was used in the following reaction without further purification.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Login to view more

Abstract

The present invention provides an isoquinoline-6-sulfonamide derivative that is useful as a novel pharmaceutical agent. The present invention provides an isoquinoline-6-sulfonamide derivative represented by Formula (1), a salt thereof, or a solvate of the derivative or the salt: wherein X and Y each independently represent a direct bond, NH, CH-CH, O, or S; R1 and R2 each independently represent a hydrogen atom, a halogen atom, a cyano group, an alkyl group, or the like; R3 and R4 each independently represent a hydrogen atom, an alkyl group, or the like, or R3 and R4 together form an alkylene group or an alkenylene group, which may be bridged between two carbon atoms to an arbitrary position; and l, m, and n represent an integer number of 1 to 4.

Description

technical field [0001] The present invention relates to isoquinoline-6-sulfonamide derivatives for the prevention and treatment of diseases or disorders caused by glaucoma, cardiovascular system diseases, neurodegeneration or nerve damage. Background technique [0002] Among compounds having an isoquinoline skeleton, there are many compounds useful as pharmaceuticals. However, there are few reports on compounds in which the 6-position of the isoquinoline skeleton is substituted by an aminosulfonyl group. The cannabinoid receptor antagonist disclosed in Patent Document 1, the mitochondrial F1FOATPase inhibitor disclosed in Patent Document 2, and the The disclosed production methods of compounds having a phenoxy group correspond to these reports. [0003] patent documents [0004] Patent Document 1: US Laid-Open Publication US-20060079556 [0005] Patent Document 2: International Publication WO2006 / 073448 [0006] non-patent literature [0007] Non-Patent Document 1: Tetr...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D217/02A61K31/407A61K31/4725A61K31/496A61K31/5377A61K31/551A61P9/00A61P25/28A61P27/06C07D401/12C07D413/12C07D487/08
CPCC07D487/08C07D401/12C07D217/02A61K31/551A61K31/496A61K31/407A61K31/5377C07D413/12C07D217/22A61K31/4725A61P9/00A61P25/00A61P25/28A61P27/06C07D217/04
Inventor 日高弘义高桥康一井上佳宏鹫见贤吾中村良平
Owner 株式会社D.西医疗法研究所
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap