5457-91-0

Upstream product

• 56-05-3 2-Amino-4,6-dichloropyrimidine 
• 109-73-9 N-butylamine 
• 1194-21-4 6-chloroisocytosine 

Downstream Products

• 6270-25-3 4-Chlor-2,5-diamino-6-butylamino-pyrimidin 
• 92298-20-9 N⁴-butyl-6-chloro-5-(4-chloro-phenylazo)-pyrimidine-2,4-diamine 
• 137932-43-5 2-Amino-4-n-butylamino-6-p-toluidinopyrimidine 

Relevant academic research and scientific papers

PYRIMIDINES AND USES THEREOF

The various examples presented herein are directed to compounds of the Formula: wherein R1-R5 are defined herein, and uses of such compounds to, among other things, inhibit an immune response in a subject.

Human Toll-like Receptor (TLR) 8-Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines

Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N4-butyl-5-iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure-activity relationship study of this chemotype was undertaken. A butyl substituent at N4 was optimal, and replacement of the 5-iodo group with chloro, bromo, or fluoro groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1β, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation.

Composition for slowing down the loss of hair based on pyrimidine N-oxides triaminosubstituted or their sulfoconjugated

Composition for slowing down the loss of hair and for inducing and stimulating its growth, comprising a compound of formula: STR1 in which: R1 and R2 denote H or an alkyl and do not simultaneously denote H; R3 and R4 denote H, an alkyl or a heterocyclic ring with the nitrogen in position 6 and do not simultaneously denote H; X denotes H or a halogen; Y denotes O or OSO3 ; and their addition salts of physiologically acceptable acids.

Small-molecule immunostimulants. Synthesis and activity of 7,8- disubstituted guanosines and structurally related compounds

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.