121288-39-9 Usage
Description
7-Allyl-7,8-dihydro-8-oxoguanosine 95, also known as Loxoribine, is a small-molecule immunostimulant derived from guanosine. It acts as a selective agonist of toll-like receptor 7 (TLR7) and is characterized by its white solid chemical properties. Loxoribine has the ability to induce immune cell activation, increase cytokine production, and enhance the immune response against tumors and viruses.
Uses
Used in Immunostimulation:
7-Allyl-7,8-dihydro-8-oxoguanosine 95 is used as an immunostimulant for enhancing the immune system's response to various pathogens and tumors. It activates immune cells, such as natural killer cells and dendritic cells, and increases cytokine production, leading to a more effective immune response.
Used in Antitumor Applications:
In the field of oncology, 7-Allyl-7,8-dihydro-8-oxoguanosine 95 is used as an antitumor agent. Loxoribine has demonstrated antitumor activity in various animal models, such as the B16 mouse model of melanoma. It reduces the number of pulmonary metastases and exhibits adjuvant activity when used in conjunction with tumor vaccines.
Used in Antiviral Applications:
7-Allyl-7,8-dihydro-8-oxoguanosine 95 also has antiviral properties, making it useful in the development of treatments for viral infections. As a TLR7 agonist, it can help the immune system recognize and respond to viral threats more effectively.
Used in Pharmaceutical Research:
In the pharmaceutical industry, 7-Allyl-7,8-dihydro-8-oxoguanosine 95 is used as a research compound for the development of new drugs targeting the immune system, cancer, and viral infections. Its unique properties as a TLR7 agonist make it a valuable tool in understanding the mechanisms of immune cell activation and cytokine production.
Used in Drug Delivery Systems:
Similar to gallotannin, Loxoribine can also be incorporated into drug delivery systems to improve its bioavailability, delivery, and therapeutic outcomes. Various organic and metallic nanoparticles can be employed as carriers for Loxoribine, enhancing its effectiveness in treating cancer and viral infections.
Biological Activity
Toll-like receptor 7 (TLR7) agonist; induces immune cell activation and increases cytokine production. Displays antitumor and antiviral activity in various animal models.
References
1) Heil?et al.?(2003),?The Tool-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily; Eur. J. Immunol.,?33?2987
2) Goodman?et al.?(1995),?A new approach to vaccine adjuvants. Immunopotentiation by intracellular T-helper-like signals transmitted by loxoribine;?Pharm. Biotechnol.,?6?581
3) Girart?et al.?(2007), Engagement of TLR3, TLR7 and NKG2D regulate IFN-gamma secretion but not NKG2D-mediated cytotoxicity by human NK cells stimulated with suboptimal doses of IL-12; J. Immunol.,?179?3472
4) Stewart?et al.?(2012),?Toll-like receptor 7 ligands inhibit influenza A infection in chickens; J. Interferon Cytokine Res,,?32?46
5) Wang?et al.?(2015),?The TLR7 agonist induces tumor regression both by promoting CD4-T cells proliferation and by reversing T regulatory cell-mediated suppression via dendritic cells; Oncotarget,?6?1779
Check Digit Verification of cas no
The CAS Registry Mumber 121288-39-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,1,2,8 and 8 respectively; the second part has 2 digits, 3 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 121288-39:
(8*1)+(7*2)+(6*1)+(5*2)+(4*8)+(3*8)+(2*3)+(1*9)=109
109 % 10 = 9
So 121288-39-9 is a valid CAS Registry Number.
InChI:InChI=1/C13H17N5O6/c1-2-3-17-6-9(15-12(14)16-10(6)22)18(13(17)23)11-8(21)7(20)5(4-19)24-11/h2,5,7-8,11,19-21H,1,3-4H2,(H3,14,15,16,22)/t5-,7-,8-,11-/m1/s1
121288-39-9Relevant articles and documents
Guanosine derivatives as immunostimulants. Discovery of loxoribine
Chen,Goodman,Argentieri,Bell,Burr,Come,Goodman,Klaubert,Maryanoff,Pope,Rampulla,Schott,Reitz
, p. 551 - 562 (1994)
7-Allyl-8-oxoguanosine (loxoribine, 5) was selected from a series of guanosine derivatives for further evaluation as an immunostimulant. Numerous related analogs were also synthesized and evaluated: 2',3'-ketals of 5 are particularly interesting because they are active, apparently without being cleaved to the free nucleoside.
Small-molecule immunostimulants. Synthesis and activity of 7,8- disubstituted guanosines and structurally related compounds
Reitz,Goodman,Pope,Argentieri,Bell,Burr,Chourmouzis,Come,Goodman,Klaubert,Maryanoff,McDonnell,Rampulla,Schott,Chen
, p. 3561 - 3578 (2007/10/02)
A series of 7,8-disubstituted guanosine derivatives was designed and prepared as potential B-cell-selective activators of the humoral immune response. These compounds were evaluated for their ability to act as B-cell mitogens and to augment the antibody response of B cells to sheep red blood cell (SRBC) challenge (adjuvanticity). In addition, they were tested for their ability to stimulate the natural killer (NK) cell response in murine in vitro cell assays. Certain of the compounds demonstrated in vivo activity when administered either intravenously, subcutaneously, or orally. Analogues with a medium-length alkyl chain (2-4 carbons, 5-7) on the 7-position of 7- alkyl-8-oxoguanosines were found to be particularly potent. Compounds bearing hydroxyalkyl, aminoalkyl, or substituted aminoalkyl substituents on this 7- position were weakly active. However, benzyl groups, including those substituted with heteroatoms (e.g., p-nitrobenzyl, 14), were active. Oxo, thioxo, and seleno groups on C-8 of the guanosine ring all imparted strong activity, whereas other larger substituents did not (e.g., N=CN). Stereochemical inversion of the 2'-hydroxyl on the ribose ring in this series, giving arabinose analogue 70, lessened activity. However, removal of the 2'-hydroxyl, either with (64) or without (73) removal of the 3'-hydroxyl, resulted in excellent activity and improved solubility; 64 also displayed good oral in vivo activity as well. A series of ketals involving the 2',3'- hydroxyls were prepared; certain of the nonpolar ketals (e.g., 48) were remarkably active, pointing to an ancillary hydrophobic binding region that can augment activity. 5'-Phosphate derivative 57 was fairly active, and acyclovir analogue 90 displayed good NK-selective activity; other N-9 sugar mimetics were also active (97-104), although this activity did not carry over into the human B-cell assay. A total of 80 compounds were prepared and evaluated for their immunostimulating activity. Within this group, compounds could be divided into those that were active in all three assays, those that displayed some measure of selectivity for the adjuvanticity assay, and those that preferentially activated NK responses. Because of its overall biological profile and ease of synthesis, 7-allyl-8-oxoguanosine (6; loxoribine, RWJ- 21757) was chosen for further development. It is among the most potent compounds evaluated in the three biological assays.
A CONVINIENT SYNTHESIS OF 7-ALLYL-8-SUBSTITUTED GUANOSINES
Come, J.,Burr, L.,Chen, R.
, p. 4823 - 4826 (2007/10/02)
An efficient and useful synthesis of 7-allyl-8-substituted guanosine derivatives has been achieved using a Claisen rearrangement as the key step.
