Unlock instant, AI-driven research and patent intelligence for your innovation.

TRPV1 antagonists including dihydroxy substituent and uses thereof

A technology of methyl and fumaric acid, applied in medical preparations containing active ingredients, anti-inflammatory agents, non-central analgesics, etc.

Inactive Publication Date: 2016-06-22
PURDUE PHARMA LP +1
View PDF50 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Medications that slow down gastrointestinal function, such as Puru, are often ineffective in treating IBS

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
  • TRPV1 antagonists including dihydroxy substituent and uses thereof
  • TRPV1 antagonists including dihydroxy substituent and uses thereof
  • TRPV1 antagonists including dihydroxy substituent and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[1011] The preparation of solvates is known in the art. For example "Preparation and Crystal Characterization of a Polymorph, a Monohydrate, and an EthylAcetate Solvate of the Antifungal Fluconazole," by Caira et al., J.Pharmaceut.Sci., 93(3) : 601-611 (2004) describes the preparation of solvates of fluconazole and ethyl acetate and with water. Similar preparations of solvates, hemisolvates, hydrates, etc. are described in "Preparation and Physical Chemical Characterization of 5 Niclosamide Solvates and 1 Hemisolvate," by Van Tonder et al. 5 (1): Article 12 (2004) and "Over one hundred solvates of sulfatethiazole," by Bingham et al., Chem. Comm., pp. 603-604 (2001). In one embodiment, a non-limiting process involves dissolving a compound of formula (I) in a desired amount of the desired solvent (organic solvent, water or a mixture thereof) at a temperature of about 20°C to about 25°C, cooling the solution The rate is sufficient to form crystals, which are isolated by known m...

Embodiment 1

[1238] 5.1 Example 1: Preparation of Compound C126(r)

[1239]

[1240] tert-butyl 4-(5-bromo-3-fluoropyridin-2-yl)-piperazine-1-carboxylate (103)

[1241] 5-Bromo-2-chloro-3-fluoropyridine (101, 8.0 g, 38.0 mmol, Oakwood Products, Inc., West Columbia, SC) in DMSO (32 mL) was mixed with tert-butylpiperazine-1-carboxylate The reaction mixture of butyl ester (102, 7.08 g, 38.02 mmol, Sigma-Aldrich) was heated at 100°C for 16 hours. The mixture was cooled to a temperature of about 25 °C, poured on cold 10% aqueous sodium carbonate and extracted with EtOAc. The organic layer was washed with water, washed with brine, dried over sodium sulfate and concentrated to afford 15.5 g of semi-solid. The semisolid was washed with hexane and filtered. The filtrate was concentrated to provide 7.5 g of residue. The residue was chromatographed on a silica gel column eluting with a gradient from 100% hexanes to 10:90 EtOAc:hexanes to afford 103 as a solid (24% yield).

[1242] (E) tert-bu...

Embodiment 2

[1254] 5.2 Example 2: Compounds B122(j), B122(k), B122(o), B122(p), B125(j), B125(k), B125(o), B125(p), B155(h) , B155(j), B155(o), B158(j), B158(o), C4(r), C123(r), C125(r) and C170(r)

[1255] The following compounds of formula (I) were prepared using procedures similar to those described in Example 1 above.

[1256] B122(j): (R)-N-(benzo[d]thiazol-2-yl)-4-{5-[(1S,2S)-1,2-dihydroxypropyl]-3-fluoropyridine -2-yl}-3-methylpiperazine-1-carboxamide.

[1257] 1 HNMR (DMSO-d 6 )δ: 0.87 (3H, d, J = 6.1Hz), 1.07 (3H, d, J = 6.4Hz), 3.08-3.45 (3H, m), 3.75-3.54 (2H, m), 3.94-4.30 (3H , m), 4.35(1H, t, J=5.0Hz), 4.66(1H, d, J=4.6Hz), 5.28(1H, d, J=4.4Hz), 7.20(1H, t, J=7.4Hz ), 7.70-7.28 (3H, m), 7.72-7.91 (1H, m), 7.96 (1H, s), 11.33 (1H, brs). LC / MS (M+1): m / z=447.

[1258] B122(k): (S)-N-(benzo[d]thiazol-2-yl)-4-{5-[(1S,2S)-1,2-dihydroxypropyl]-3-fluoropyridine -2-yl}-3-methylpiperazine-1-carboxamide.

[1259] 1 HNMR (DMSO-d 6 )δ: 0.87 (3H, d, J = 6.4Hz), 1.07 (3H, d, J =...

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 invention relates to a TRPV1 antagonists including a dihydroxy substituent and uses thereof. The disclosure relates to Compounds of Formula (I) and pharmaceutically acceptable derivatives thereof, where R1, R4, R8, R9, and m are as defined herein, compositions comprising an effective amount of a Compound of Formula (I) or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, pain associated with osteoarthritis, osteoarthritis, UI, an ulcer, IBD, and IBS, comprising administering to an animal in need thereof an effective amount of a Compound of Formula (I) or a pharmaceutically acceptable derivative thereof.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of June 21, 2012, an application number of "201280030744.7", and an invention title of "TRPV1 antagonist containing a dihydroxy substituent and its use". The original application is an international Application for PCT / IB2012 / 001252 Chinese national phase application. technical field [0002] The present invention relates to compounds of formula (I) and pharmaceutically acceptable derivatives thereof, compositions comprising effective doses of compounds of formula (I), and treatments or preventions such as pain (such as pain associated with osteoarthritis), osteoarthritis A method for conditions of arthritis, UI, ulcer, IBD and IBS, comprising administering an effective amount of a compound of formula (I) or a pharmaceutically acceptable derivative thereof to an animal in need thereof. Background technique [0003] Pain is the most common symptom for which patients se...

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): C07D417/12C07D417/14A61K31/496A61P29/00A61P1/04A61P13/00A61P25/02A61P25/04A61P19/02
CPCC07D417/12C07D417/14A61K31/428A61K31/496A61P1/00A61P1/04A61P13/00A61P19/00A61P19/02A61P25/00A61P25/02A61P25/04A61P29/00A61P43/00C07C57/15C07C59/255C07C309/29C07C309/30
Inventor 莱基·塔费塞安藤茂黑濑规之
Owner PURDUE PHARMA LP