69790-73-4

Upstream product

• 21871-44-3 5-(3-nitrophenyl)-1H-tetrazole 
• 74-88-4 methyl iodide 
• 18039-42-4 5-phenyl-2H-1,2,3,4-tetrazole 
• 100-47-0 benzonitrile 
• 20743-49-1 2-methyl-5-phenyl-2H-tetrazole 
• 619-24-9 3-nitrobenzonitrile 
• 78137-21-0 C₇H₄N₅O₂^(1-)*K⁽¹⁺⁾ 
• 77-78-1 dimethyl sulfate 

Downstream Products

• 73732-51-1 5-(3-aminophenyl)-1H-tetrazole 
• 1448724-39-7 2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-ol 

Relevant academic research and scientific papers

Gram-Scale Laboratory Synthesis of UM171, a Potent Agonist of Human Hematopoietic Stem Cell Self-Renewal

A short economic synthesis of pyrimidoindole derivative UM171, a potent agonist for the ex vivo expansion of hematopoietic stem cells, has been developed in this work. A unique [3,3]-sigmatropic rearrangement upon a hydroxamic precursor followed by base-promoted cyclization was successfully applied as the key step, furnishing the fully functionalized indole nucleus. The current synthesis is not only capable of affording UM171 in gram quantities but also offers great flexibility in late-stage diversification. Three new analogues of UM171 were synthesized accordingly in excellent yields using the common indole-carboxamide intermediate.

Anti-tumor metastasis effect of 2, 4, 7-trisubstituted pyrimidino indole compound

The invention relates to a compound with a 2, 4, 7-trisubstituted pyrimidino indole structure. The compound can inhibit tumor cell migration and invasion at a very low concentration, and has an effect superior to that of a clinically common drug cis-platinum. In addition, the compound can also inhibit the expression of matrix metalloproteinase related protein which plays an important role in tumor migration and invasion processes. The invention also relates to a preparation method of the compound and application of the compound in marking, diagnosis, prevention and treatment or adjuvant therapy of tumors.

Antitumor effect of 2, 4, 7-trisubstituted pyrimidino indole compound

The invention relates to a series of compounds with 2, 4, 7-trisubstituted pyrimidino indole structures, and the compounds can inhibit the growth of various tumor cells, and particularly, the compounds can efficiently inhibit the proliferation of breast cancer, cervical cancer, gastric adenocarcinoma and liver cancer cells. In addition, the compound can inhibit tumor cell clone formation at a very low concentration and promote tumor cell apoptosis. The invention also relates to a preparation method of the compound and application of the compound in marking, diagnosis, prevention and treatment or adjuvant therapy of tumors.

2, 4, 7 -substituted pyrimido indole compound antitumor drug resistance effect

The invention relates to 2, 4 and 7 - tri-substituted pyrimido-indole structural compounds which can inhibit the growth of various drug-resistant tumor cells, and in particular, can efficiently inhibit doxorubicin resistant breast cancer. Cisplatin-resistant lung cancer and cisplatin liver cancer cell proliferation. In addition, the compounds of the present invention can inhibit the formation of drug-resistant tumor cell clones at very low concentrations and inhibit P glycoprotein and ABCG2 transport in vitro functions. The invention also relates to a preparation method of the compound and an application of the compound in tumor treatment or adjuvant therapy.

Ruthenium-Catalyzed meta-Selective C?H Nitration of Biologically Important Aryltetrazoles

The first example of tetrazole-directed meta-selective C?H nitration is described. This transformation provided a straightforward approach for the synthesis of biologically important m-nitroaryltetrazoles in moderate to excellent yields with good functional group compatibility. In addition, new metallo-β-lactamase inhibitors were obtained by further transformation of the synthesized m-nitroaryltetrazoles. (Figure presented.).

Discovery of mercaptopropanamide-substituted aryl tetrazoles as new broad-spectrum metallo-β-lactamase inhibitors

β-Lactam antibiotic resistance mediated by metallo-β-lactamases (MBL) has threatened global public health. There are currently no available inhibitors of MBLs for clinical use. We previously reported the ruthenium-catalyzed meta-selective C-H nitration synthesis method, leading to some meta-mercaptopropanamide substituted aryl tetrazoles as new potent MBL inhibitors. Here, we described the structure-activity relationship of meta- and ortho-mercaptopropanamide substituted aryl tetrazoles with clinically relevant MBLs. The resulting most potent compound 13a showed IC50 values of 0.044 μM, 0.396 μM and 0.71 μM against VIM-2, NDM-1 and IMP-1 MBL, respectively. Crystallographic analysis revealed that 13a chelated to active site zinc ions via the thiol group and interacted with the catalytically important residues Asn233 and Tyr67, providing further structural information for the development of thiol based MBL inhibitors. This journal is

Novel tetrazole-oriented meta-position nitration C-H activation method

The invention provides a novel tetrazole-oriented meta-position-selective C-H nitration method. The method comprises the following steps: by taking a 5-phenyl tetrazole compound as a raw material, carrying out meta-position nitration catalyzed by transiti

Synthesis and evaluation of pyrimidoindole analogs in umbilical cord blood ex vivo expansion

The scarcity of hematopoietic stem cells (HSCs)significantly hindered their clinical potentials. Umbilical cord blood (UCB)has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients. Various cytokines and small molecules have demonstrated strong abilities in promoting HSC ex vivo expansion, of which UM171 is the newest and by far the most potent HSC ex vivo expansion agent. In this study, we synthesized 37 pyrimidoindole analogs and identified 6 compounds to be potent in promoting HSC ex vivo expansion. In particular, analog 11 was found to be the most effective in stimulating ex vivo expansion of UCB CD34+ cells and CD34+CD38? cells. Initial data indicated that compound 11 promoted the absolute number of long term HSCs and inhibited their differentiation. UCB HSCs expanded with 11 retained adequate multi-lineage differentiation capacity. In addition, compound 11 is not cytotoxic at its test concentrations, suggesting that it merits further investigation for potential clinical applications.

Pyrimidinoindole compound as well as preparation method and application thereof

The invention relates to the technical field of medicine chemistry and in particular to a pyrimidinoindole compound as well as a preparation method and application thereof. The invention mainly relates to synthesis of a pyrimidinoindole-containing compoun

INHIBITORS OF NECROPTOSIS

The invention relates to novel heterocyclic compounds of Formula (I) which inhibit necroptosis and methods for their use. The compounds may be useful in the treatment of conditions associated with deregulated necroptosis.