Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Substituted octahydrocyclopentadieno(c)pyrrol-4-amines as calcium channel blockers

A technology of octahydrocyclopentadiene and trityl octahydrocyclopentadiene, applied in the field of substituted octahydrocyclopentadiene (C) pyrrol-4-amine as a calcium channel blocker, capable of Solve the problem of no effect, no effect of thermal hyperalgesia, etc.

Inactive Publication Date: 2011-12-21
ABBVIE INC
View PDF4 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In contrast, intrathecal delivery of the selective P / Q-type blocker ω-funnel toxin IVA had no effect on mechanical allodynia in a spinal nerve ligation model (Chaplan, S. R. et al., Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia. J. Pharmacol. Exp. Ther. 1994, 269(3), 1117-1123) or no effect on thermal hyperalgesia in a chronic crush injury model (Yamamoto, T. et al., Differential effects of intrathecally administered N- and P-type voltage-sensitive calcium channel blockers upon two models of experimental mononeuropathy in the rat. Brain Res. 1998, 794(2), 329-332)

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 octahydrocyclopentadieno(c)pyrrol-4-amines as calcium channel blockers
  • Substituted octahydrocyclopentadieno(c)pyrrol-4-amines as calcium channel blockers
  • Substituted octahydrocyclopentadieno(c)pyrrol-4-amines as calcium channel blockers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1 and Embodiment 2

[0830] N -[(3a S *, 4 S *, 6a R *)-2-benzyl octahydrocyclopenta[ c ]Pyrrol-4-yl]-1-phenylcyclopentanecarboxamide (Example 1) and

[0831] N -[(3a S *, 4 R *, 6a R *)-2-benzyl octahydrocyclopenta[ c ]Pyrrol-4-yl]-1-phenylcyclopentanecarboxamide (Example 2)

[0832] Combine 1-hydroxybenzotriazole (33 mg, 0.24 mmol) and N -(3-Dimethylaminopropyl)- N '-Ethylcarbodiimide (43 μL, 0.24 mmol) was added to 1-phenylcyclopentanecarboxylic acid (46 mg, 0.24 mmol) in dichloromethane (2 mL). Stir the reaction at room temperature for 10 minutes, then add (3a S *, 6a R *)-2-benzyl octahydrocyclopenta[ c ]Pyrrol-4-amine (52 mg, 0.24 mmol) and the reaction was stirred overnight at room temperature. The reaction was terminated with water and extracted with dichloromethane, and then chromatographed on silica gel with 1-10% methanol (2 N Ammonia / chloroform was used as the eluent to obtain the title compound.

Embodiment 1

[0833] Example 1: 1 H NMR (500 MHz, pyridine -d 5 ) δ ppm 7.52-7.28 (m, 9H), 7.25 (d, J = 7.7, 1H), 4.43-4.34 (m, 1H), 3.56 (d, J = 12.9, 1H), 3.17 (d, J = 12.9, 1H), 2.83-2.67 (m, 2H), 2.59-2.50 (m, 1H), 2.50-2.44 (m, 1H), 2.35-2.29 (m, 2H), 2.04-1.87 (m, 4H) , 1.84-1.54 (m, 6H), 1.43-1.26 (m, 1H), 1.04-0.94 (m, 1H); MS (ESI+) m / z 389 (M+H) + .

Embodiment 2

[0834] Example 2: 1 H NMR (500 MHz, pyridine -d 5 ) δ ppm 7.52-7.47 (m, 2H), 7.41 (d, J = 7.4, 2H), 7.38-7.29 (m, 4H), 7.25 (q, J = 7.3, 2H), 4.36 (m, 1H), 3.57 (d, J = 13.2, 1H), 3.40 (d, J = 13.2, 1H), 2.78 (m, 3H), 2.33 (m, 3H), 2.27 (d, J = 8.7, 1H), 2.21-2.13 (m, 1H), 1.99 (dt, J = 5.8, 11.7, 3H), 1.87-1.75 (m, 2H), 1.71-1.60 (m, 3H), 1.44 (ddd, J = 7.7, 12.1, 14.5, 1H), 1.31 (m, 1H); MS (ESI+) m / z 389 (M+H) + .

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

No PUM Login to View More

Abstract

The present invention relates to a calcium channel inhibitor comprising a compound of formula (I), wherein L1, L2, R1, R2 and R3 are as defined in the specification. The invention also relates to compositions comprising such compounds and methods of using such compounds and compositions to treat diseases and conditions. (I)

Description

Technical field [0001] The present invention relates to compounds as calcium channel blockers, compositions containing such compounds, and methods of using such compounds and compositions to treat diseases and disorders. Background technique [0002] Voltage-gated calcium channels (VGCC) play an overall role in the regulation of membrane ion conduction, neurotransmitter release and cell excitability. VGCC is composed of pore-forming α1 subunit and auxiliary α2δ and β subunits that regulate channel expression and functionality (Dolphin, AC A short history of voltage-gated calcium channels. British Journal of Pharmacology 2006, 147 (Suppl. 1), S56-S62). These channels can be classified as low voltage activated (LVA; T-type or Ca v 3.x) and high voltage activated (HVA; L-type or Ca v 1.x and N-, P / Q- and R-type or Ca v 2.x) Channel. Typically, N-, P / Q and R channels are activated at a corrected membrane potential (~ -30 mV) and participate in "presynaptic" neurotransmission (McGiv...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/02A61K31/403
CPCC07D209/02A61P11/00A61P11/06A61P13/00A61P13/08A61P15/00A61P17/00A61P17/04A61P25/00A61P25/02A61P25/04A61P25/06A61P25/08A61P25/16A61P25/18A61P25/22A61P25/24A61P25/28A61P25/30A61P25/32A61P29/00A61P29/02A61P35/00A61P37/00A61P37/08A61P43/00A61P9/00A61P9/04A61P9/06A61P9/10A61P9/12A61P3/10C07D209/52A61K31/403
Inventor A.斯特瓦特X.西尔勒D.达扎克杨铭S.迪多梅尼科
Owner ABBVIE INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com