Tenofovir disoproxil fumarate compounds, preparation method and application to antiviral field
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 tenofovir disoproxil and compounds, applied in the field of nucleoside compounds
Active Publication Date: 2013-08-14
洛阳聚慧新材料科技有限公司 +2
View PDF6 Cites 6 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
However, the fat solubility of the above two prodrugs still needs to be further improved, so as to improve the bioavailability of the human body
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
[0067] Embodiment 1: the preparation of 3-hexadecyloxy-1-propanol (L114)
[0068]
[0069] In a 250ml three-neck round bottom flask, add 1,3-propanediol (9.13g, 0.12mol), potassium tert-butoxide (6.8g, 0.06mol) and tert-amyl alcohol (50ml) in sequence, and slowly add A mixture of hexadecane bromide (12.17g, 12.2ml, 0.04mol) and tetrahydrofuran (50ml) was added dropwise over 3 hours. After refluxing and stirring for 50 hours, cool to room temperature, pour the reaction solution into 50ml of water, stir, acidify with 10% hydrochloric acid to pH=7, add n-hexane (100ml), separate the organic phase, and extract the aqueous phase with n-hexane , the organic phases were combined, dried and concentrated, and then recrystallized with n-pentane to obtain 3-hexadecyloxy-1-propanol (L114) (7.8 g, 0.026 mol), yield: 65%. 1 H NMR (400MHz, CDCl 3 )δ,(ppm):0.88(3H,t,CH 3 ),1.14-1.37(26H,m,13×CH 2 ),1.48-1.65(2H,m,CH 2 ), 1.71-1.94 (2H, m, CH 2 ),2.38-2.53(1H,br,OH),3.43(2H,t,OCH 2 )...
Embodiment 2
[0070] Embodiment 2: the preparation of 2-octadecyloxyethanol (L016)
[0071]
[0072] Synthesized in a similar manner to Example 1 to obtain 2-octadecyloxyethanol (L016). 1 H NMR (400MHz, CDCl 3 )δ,(ppm):0.88(3H,t,CH 3 ),1.06-1.49(30H,m,15×CH 2 ), 1.53-1.654 (2H, m, CH 2 ), 1.90-2.10 (1H, br, OH), 3.47 (2H, t, OCH 2 ),3.53(2H,t,OCH 2 ),3.73(2H,t,OCH 2 ). ESI-MS:[M+H] + 315.3, [M+Na] + 337.3.
Embodiment 3
[0073] Example 3: Preparation of 6-dodecyloxy-1-hexanol (L410)
[0074]
[0075] 6-dodecyloxy-1-hexanol (L410) was synthesized in a similar manner to Example 1. 1 H NMR (400MHz, CDCl 3 )δ,(ppm):0.88(3H,t,CH 3 ),1.14-1.34(18H,m,9×CH 2 ),1.35-1.42(4H,m,2×CH 2 ),1.48-1.64(6H,m,3×CH 2 ),1.93-2.01(1H,br,OH),3.28-3.48(4H,m,2×OCH 2 ),3.62(2H,t,OCH 2 ). ESI-MS:[M+H] + 287.3, [M+Na] + 309.3.
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 group of tenofovir disoproxil fumarate compounds with activity for inhibiting HIV(human immunodeficiency virus) /HBV(Hepatitis B Virus) replication, a preparation method and pharmaceutical application of the group of tenofovir disoproxil fumarate compounds. The compounds have a formula I, wherein X=H, Y=H; R1=-CH2(CH2)mCH2OCH2(CH2)nCH3, wherein m ranges from 0 to 4, and n ranges from 10 to 20; and R2=-OCH2OC(O)OCH(CH3)2. The invention also discloses a pharmaceutical composition containing the compounds. Shown by the experiment, the activity of one of the compounds for inhibiting the replication of HIV-1 (Human Immunodeficiency Virus-1) is 4.5 times that of azidothymidine (AZT), about 250 times that of the tenofovir disoproxil fumarate (TDF) which is the best medicine for treating acquired immunodeficiency syndrome at present, and 1.37 times that of the medicine CMX157 (Cefmenoxime) which comes into the clinical stage, and the lipid solubility of the compound is about 2 times that of the CMX157; the compounds also have the activity for inhibiting the replication of HBV (Hepatitis B Virus); and the compounds can be applied to the development of medicines for treating the acquired immune deficiency syndrome/hepatitis B.
Description
Technical field: [0001] The invention relates to a group of nucleoside compounds, in particular to a group of tenofovir disoproxil compounds with the activity of inhibiting HIV-1 virus replication, a preparation method and an antiviral application thereof. Background technique: [0002] In the treatment of viral infectious diseases in humans, the problem of viral drug resistance has become increasingly prominent. Compared with cyclic nucleoside reverse transcriptase inhibitors, adefovir and tenofovir, acyclic nucleoside compounds, have obvious advantages in preventing viral drug resistance. The virus strain is effective, the incidence of drug resistance itself is low, and the toxicity is relatively small, so it can be used to treat patients infected with HIV-1. However, because the phosphate group is negatively charged, the polarity is too strong, and the biofilm permeability is poor, resulting in low bioavailability, so that it cannot be used as a drug for clinical use. It...
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