Anti-inflammatory compounds and uses thereof
A technology for compounds and drugs, applied in phosphorus organic compounds, applications, anti-inflammatory agents, etc., can solve problems such as non-conformance and limited sequences
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0153] Embodiment 1. synthetic method
[0154] The present compound 5 (p-aspirin phosphate) shown below was obtained according to the following reaction scheme. Compound 5 was synthesized from o-acetylsalicyloyl chloride (1) and 4-hydroxybenzaldehyde (2) in three steps as shown below.
[0155]
[0156] In this scheme, -OEt represents CH 3 CH 2 O-.
[0157] Step 1: Preparation of compound 3: 4-Hydroxybenzaldehyde (2, 1.04 g, 8.49 mmol) in dichloromethane (10 mL) and pyridine (4.16 mL, 50 moles) were pre-cooled (0 °C) solution was added dropwise o-acetyl salicyloyl chloride (1, 1.98 g, 10 mmol) prepared in dichloromethane (10 mL). The temperature of the reaction mixture was slowly raised to room temperature and left overnight. At this point, TLC of the reaction mixture showed the reaction was complete. Water (25mL), 1N HCl (25mL) and aqueous NaHCO 3 The reaction mixture was washed. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. ...
Embodiment 4
[0181] Embodiment 4. Compared with the parent compound, the antitumor ability of 6 kinds of NSAID-based novel compounds is significantly improved
[0182] According to Penning et al. (Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S, etc., Synthesis and biological evaluation of the1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl) Synthesis and biological evaluation of 3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonesulfonamide (SC-58635, celecoxib) (1,5-diarylpyrazol-like cyclooxygenase-2 inhibitors: 4 Identification of -[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, celecoxib).J Med Chem 1997; 40: 1347-65) and the method described here, based on 4 representative NSAIDs: aspirin (2 derivatives with different linkers), ibuprofen, flurbiprofen and sulindac (sulindac 2 derivatives with different acid moieties) to synthesize 6 compounds. Their structures and NMR patterns are sho...
Embodiment 5
[0199] Example 5: Phospho-sulindac I inhibits colon cancer growth in vivo
[0200] In two animal models of colon cancer (APC Min / + The effect of phospho-sulindac I on tumor growth was assessed in colon cancer xenografts in mice and nude mice).
[0201] APCs Min / + Mouse studies: Min mice have a truncating mutation in the Apc gene that predisposes them to develop gastrointestinal tumors in the small intestine and colon (Lipkin M, Yang K, Edelmann W et al, Preclinical mouse models for cancer chemoprevention studies (Cancer Preclinical mouse models for chemoprevention studies). Ann N Y Acad Sci 1999;889:14-9). This model system represents a useful (and widely used) experimental system for describing colon cancer-related steps in many important ways.
[0202] 11-week-old male C57BL / 6J APC Min / + Mice were divided into 4 groups of 10 and treated by gavage for 4 weeks as follows: Group 1 was treated with vehicle (corn oil); Group 2 was treated with phospho-sulindac I at 50 mg / kg / d...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More