91066-67-0

Upstream product

• 56-05-3 2-Amino-4,6-dichloropyrimidine 
• 100-46-9 benzylamine 

Downstream Products

• 186416-91-1 2-amino-4-benzylamino-5-(p-chlorophenylazo)-6-chloropyrimidine 
• 17756-35-3 9-benzyl-8-azaguanine 
• 186416-92-2 2,5-diamino-4-benzylamino-6-chloropyrimidine 
• 186416-93-3 3-Benzyl-7-chloro-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-ylamine 
• 1026432-04-1 2-Amino-9-benzyl-6-chloro-7,9-dihydro-purin-8-one 
• 1026300-25-3 7-Allyl-2-amino-9-benzyl-6-chloro-7,9-dihydro-purin-8-one 
• 1227909-25-2 4-{2-amino-6-[(phenylmethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrile 
• 244288-47-9 2-Amino-6-benzylamino-4-cyclohexylmethyloxy pyrimidine 

Relevant academic research and scientific papers

Heterocyclic compounds as well as preparation method and application thereof

The invention belongs to the field of medicines and particularly relates to heterocyclic compounds with the structural characteristics shown in formula (I) or pharmaceutically acceptable salts, a preparation method and an application of the heterocyclic compounds as a nucleotide oxidative damage repairase MTH1 inhibitor. Pharmacological experiment results indicate that the compounds have significant inhabitation effects on the activity of MTH1 and can be used for preventing and treating clinical diseases related to MTH1.

An efficient and simple methodology for the synthesis of 2-amino-4-(N-alkyl/arylamino)-6-chloropyrimidines

In this study, twenty-nine 2-aminopyrimidine derivatives are synthesized in good to excellent yields by fusing 2-amino-4,6-dichloropyrimidine with different amines in the presence of triethylamine without using any solvent or catalyst. Nucleophilic substitution reactions of 2-amino-4,6-dichloropyrimidine with amines have also been performed in ethanol. Comparisons of the yields and reaction times for both solvent and solvent-free conditions have shown that the newly developed solvent-free protocol is high yielding, more efficient, and simpler compared to conventional methods.

Triamino pyrimidines and pyridines as histamine H4 receptor modulators

Two series of triamino pyrimidines and a series of triamino pyridines have been synthesized and their structure-activity relationships evaluated for activity at the H4 receptor in competitive binding and functional assays. Small structural changes in these three hetereoaromatic cores influenced the functional activity of these compounds.

CHEMICAL COMPOUNDS

The invention is directed to 6-(4-pyι?midinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

2,4-Diaminopyrimidines as histamine H4 receptor ligands-Scaffold optimization and pharmacological characterization

The human histamine H4 receptor (hH4R) is a promising new target in the therapy of inflammatory diseases and disorders of the immune system. For the development of new H4R antagonists a broad ligand-based virtual screening was performed resulting in two hits. The dissection of their common annelated aromatic core into its heteromonocyclic components showed that 2,4-diaminopyrimidine is a potent hH4R affinity scaffold, which was comprehensively investigated. Structure-activity relationship studies revealed that slight structural changes evoke extensive differences in functional activities and potencies: while o- and p-substituted benzyl amines mainly showed partial agonism, m-substituted and rigidified ones exhibited inverse agonist efficacy.

Cyclin dependent kinase inhibitors

A range is disclosed of pyrimidine derivatives (I) which can act as inhibitors of cyclin dependent kinases (CDK's) and which thereby can provide useful therapeutic compounds for use in treatment of tumours or other cell proliferation disorders. The compounds of this invention bind to CDK molecules in a manner that appears to differ from that of known CDK inhibitors such as olomoucine and roscovitine. In formula (I), X is O, S or CHRxwhere Rxis H or C1-4alkyl; D is H or NZ1Z2where Z1and Z2are each independently H, C1-4alkyl, C1-4hydroxyalkyl, optionally substituted aryl or optionally substituted aralkyl; A is selected from H, C1-4alkyl, C1-4alkoxy, hydroxy, CH2(CH2)nOH (n=1-4), and NRa1Ra2where Ra1and Ra2are each independently H or C1-4alkyl; Y is or includes an optionally substituted 4- to 8-membered carbocyclic or heterocyclic ring; D′ is H or NZ3Z4where Z3and Z4are each independently H, C1-4alkyl, C1-4hydroxyalkyl, optionally substituted aryl or optionally-substituted aralkyl; E is selected from NO, NO2, N═N—Ar where Ar is an optionally substituted aryl or optionally substituted aralkyl, NRe1Re2or Nre1Nre2Re3(Re1, Re2and Re3each being independently H, C1-4alkyl, C1-4hydroxyalkyl, an optionally substituted aryl or an optionally substituted aralkyl), C(Re)═U (Rebeing hydrogen, C1-4alkyl or substituted alkyl, e.g. hydroxyalkyl, or an unsubstituted or substituted aryl or aralkyl, e.g. benzyl, and U being selected from O, Nre′, NORe′ and N—NRe′Re″ where Re′ and Re″ are each independently H, C1-4alkyl or CONH2), T, CH2T, CHT2and CT3, where T is a halide I, Br, Cl or F.

Regioselective synthesis of 9-substituted-8-azaguanines (5-amino-3-substituted-3,6-dihydro-7H-1,2,3-triazolo[4,5-d]pyrimidin-7 -one)

By modifying previously described methods for the synthesis of 9-substituted-guanines from imidazoles, we have developed a new procedure for the regioselective synthesis of 9-substituted-8-azaguanines (5-amino-3-substituted-3,6-dihydro-7H- 1,2,3-triazolo[4,5-d]pyrimidin-7-one) from triazoles in high yields. The method seems suitable for the introduction of a variety of substituents including sugars, carbocyclic, acyclic and carboacyclic chains.

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.