Unlock instant, AI-driven research and patent intelligence for your innovation.
3-(naphthalene-1-methyl substituted) pyridine derivative and synthesis method and application thereof
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A technology of derivatives and pyridine, applied in new compounds and their application fields, can solve problems such as no alternative drugs, low activity, and large toxic and side effects
Active Publication Date: 2018-08-24
SOUTHERN MEDICAL UNIVERSITY
View PDF3 Cites 0 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
[0004] Benzbromarone is currently the most effective uricosuric drug, but it has severe side effects, especially can cause fulminant hepatitis, so it has not been approved by the FDA to be marketed in the United States, and it was once stopped in Europe because there is no more suitable drug. Alternative drugs, except in France, are currently in clinical use again
In December 2015, the first selective inhibitor targeting hURAT1, Lesinurad, was approved by the FDA, but its activity is much lower than that of benzbromarone (about 1 / 100)
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
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0044] Synthesis of 2-[[3-[(4-cyanonaphthalen-1-yl)methyl]pyridin-4-yl]thio]acetic acid (Ia-1):
[0045] 1) Synthesis of 4-(4-chloronicotinoyl)-1-naphthalenecarbonitrile (compound 3a-1)
[0046]
[0047] Add magnesium chips (58mg, 2.4mmol) and catalytic amount of iodine particles in a three-necked flask equipped with a reflux condenser and a constant pressuredropping funnel, heat until the surface of the magnesium chips is purple, then add a small amount of tetrahydrofuran to cover the magnesium chips . 3-Bromo-4-chloropyridine (384mg, 2mmol) was dissolved in 5ml of tetrahydrofuran, and a small amount was added dropwise into a three-neck flask, and after being slightly heated to initiate the reaction, the remaining solution was slowly dropped into. After dropping, the reaction bottle was kept at 40° C. for 2 hours, and allowed to stand still to return to room temperature. 356mg (2mmol) of 1,4-dicyanonaphthalene and 20mL of tetrahydrofuran were cooled to 0°C, and the abov...
Embodiment 2
[0062] Synthesis of 2-[[3-[(4-fluoronaphthalen-1-yl)methyl]pyridin-4-yl]thio]acetic acid (Ia-2):
[0063]
[0064] The target compound Ia-2 was synthesized according to the synthesis method of the target compound Ia-1, and the yield was 88%.
[0065] 1 H NMR (400MHz, DMSO-d 6 )δ12.90(bs,1H),8.63(d,J=5.3Hz,1H),8.49(s,1H),8.29-8.21(m,2H),7.83-7.70(m,1H),7.63-7.57 (m,1H),7.45(d,J=7.0Hz,1H),7.40(d,J=5.3Hz,1H),7.30(d,J=7.5Hz,1H),5.70(s,2H),4.32 (s,2H).ESI-MS m / z: 326.4[M-H]-.
Embodiment 3
[0067] Synthesis of 2-[[3-[(4-chloronaphthalen-1-yl)methyl]pyridin-4-yl]thio]acetic acid (Ia-3):
[0068]
[0069] The target compound Ia-3 was synthesized according to the synthesis method of the target compound Ia-1, and the yield was 93%. 1 H NMR (400MHz,
[0070] 1 H NMR (400MHz, DMSO-d 6 )δ13.19(bs,1H),8.65(d,J=5.5Hz,1H),8.46(s,1H),8.40-8.24(m,2H),7.80-7.71(m,1H),7.65-7.56 (m,1H),7.50(d,J=7.3Hz,1H),7.43(d,J=5.4Hz,1H),7.38(d,J=8.3Hz,1H),5.62(s,2H),4.32 (s,2H).ESI-MS m / z:342.6[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
Login to View More
Abstract
The invention discloses a 3-(naphthalene-1-methyl substituted) pyridine derivative and a synthesis method and application thereof. The derivative comprises a compound having a structural formula as shown in the specification, or a pharmaceutically acceptable salt, hydrate, solvate, polymorphic substance, tautomer, stereoisomer or prodrug thereof, the derivative has high hURAT1(human urate transporter) inhibitory activity, has strong uric acid transport inhibitory activity of MDCK-hURAT1 cells, can be used for preparation of drugs for treatment and / or prevention and / or delay and / or adjuvant treatment and / or treatment of diseases associated with hURAT1 (human urate transporter) transport uric acid, especially hyperuricemia. By combining with other drugs for treatment of the hyperuricemia,the derivative is expected to achieve better therapeutic effects on the hyperuricemia.
Description
technical field [0001] The present invention relates to novel compounds and their applications, in particular to 3-(naphthalene-1-methyl-substituted) pyridine derivatives and their synthesis methods and applications. Background technique [0002] The reduction of uric acidexcretion is the main cause of hyperuricemia. The incidence of gout caused by uric acid has increased significantly in recent years, and it tends to be younger, which makes people pay more and more attention to the treatment of gout. [0003] 2 / 3 of the urate in the human body is excreted through the kidneys, and most of the urate filtered by the kidneys is reabsorbed by the human body. Human urate transporter 1 (hURAT1, human urate transporter 1) is a urate transporter located at the brush border of renal tubular epithelial cells, and belongs to the SLC22 family of organic anion transporters (OATs). This transporter can promote the reabsorption of uric acid by renal tubules and determine how much uric a...
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
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to View More 
Login to View More