21253-58-7

Usage

Uses

Used in Pharmaceutical Industry:
4-DeMethyltriMethopriM is used as an impurity in the production of Trimethoprim, an antibacterial agent. Its presence, although not desired, is a part of the synthesis process of the active pharmaceutical ingredient, Trimethoprim. The pharmaceutical industry aims to minimize the presence of this impurity to ensure the safety and efficacy of the final product.
Used in Research and Development:
4-DeMethyltriMethopriM can be used as a subject of study in research and development for understanding the synthesis process, impurity profiling, and potential effects on the efficacy and safety of Trimethoprim. This knowledge can contribute to the improvement of manufacturing processes and the development of new, more effective antibacterial agents.
Used in Quality Control:
In the quality control process of pharmaceutical manufacturing, 4-DeMethyltriMethopriM is used as a reference compound to test and ensure the purity of Trimethoprim. By monitoring the levels of this impurity, manufacturers can maintain the quality and consistency of their products, ensuring that they meet regulatory standards and are safe for use.

Upstream product

• 156-81-0 2,4-diaminopyrimidine 
• 39667-14-6 2,6-dimethoxy-4-<(N,N-dimethylamino)methyl>phenol 
• 738-70-5 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine 

Downstream Products

• 78025-76-0 [4-(2,4-Diamino-pyrimidin-5-ylmethyl)-2,6-dimethoxy-phenoxy]-acetic acid ethyl ester 
• 94236-26-7 5-[4-(2,4-Diamino-pyrimidin-5-ylmethyl)-2,6-dimethoxy-phenoxy]-pentanoic acid methyl ester 
• 94236-25-6 4-[4-(2,4-Diamino-pyrimidin-5-ylmethyl)-2,6-dimethoxy-phenoxy]-butyric acid ethyl ester 
• 78025-88-4 6-[4-(2,4-Diamino-pyrimidin-5-ylmethyl)-2,6-dimethoxy-phenoxy]-hexanoic acid methyl ester 
• 111453-14-6 5-{3,5-Dimethoxy-4-[4-(4-nitro-benzenesulfonyl)-benzyloxy]-benzyl}-pyrimidine-2,4-diamine 
• 111452-95-0 K-122 
• 111452-92-7 K-150 
• 111452-84-7 5-(3,5-Dimethoxy-4-{3-[4-(4-nitro-benzenesulfonyl)-phenylamino]-propoxy}-benzyl)-pyrimidine-2,4-diamine 
• 78025-91-9 5-(3,5-Dimethoxy-4-oxiranylmethoxy-benzyl)-pyrimidine-2,4-diamine 
• 738-70-5 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine 
• 176512-50-8 2,4-diamino-5-<3,5-dimethoxy-4-<2-(4'-(2''-methyl-4''-nitrophenyl)sulfonylanilino)ethoxy>benzyl>pyrimidine 
• 176512-48-4 2,4-diamino-5-<3,5-dimethoxy-4-<3-(4'-(2''-methyl-4''-nitrophenyl)sulfonylanilino)propoxy>benzyl>pyrimidine 
• 176512-49-5 2,4-diamino-5-<3,5-dimethoxy-4-<3-(3'-methyl-4'-(4''-nitrophenyl)sulfonylanilino)propoxy>benzyl>pyrimidine 
• 172797-80-7 2,4-diamino-5-<3,5-dimethoxy-4-<3-(4'-amidoanilino)propoxy>benzyl>pyrimidine 

Relevant academic research and scientific papers

Reversible optogenetic control of protein function and localization

Protein-protein interactions are highly dynamic biological processes that regulate various cellular reactions. They exhibit high specificity and spatiotemporal control in order to efficiently utilize finite resources in a cellular compartment. Photoactivatable chemically inducible dimerization (pCID) has emerged as an attractive technique in the scientific community, leading to the development of systems that can be activated with various wavelengths of light in order to manipulate processes on biologically relevant scales with molecular specificity. These systems can be modified to control various protein functions with unprecedented precision and spatiotemporal resolution. In this chapter, we describe an optogenetic platform that provides reversible control over dimerization of genetically tagged proteins using orthogonal wavelengths of light. We demonstrate photoactivation and photo-reversal of protein localization and transport. Mitosis is manipulated by activating and silencing the spindle assembly checkpoint through recruitment and release of proteins from kinetochores.

Modulation of BCR signaling by the induced dimerization of receptor-associated SYK

Clustering of the B cell antigen receptor (BCR) by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, we developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, we fused SYK with E. coli dihydrofolate reductase (eDHFR), which binds the small molecule trimethoprim (TMP) with high affinity and selectivity and synthesized a dimer of TMP with a flexible linker. The TMP dimer is able to induce the aggregation of eDHFR-linked SYK in live cells. The induced dimerization of SYK bound to the BCR differentially regulates the activation of downstream transcription factors, promoting the activation of Nuclear Factor of Activated T cells (NFAT) without affecting the activation of NFκB. The dimerization of SYK enhances the duration but not the amplitude of calcium mobilization by enhancing the extent and duration of its interaction with the crosslinked BCR at the plasma membrane.

Broad-spectrum monoclonal antibody and a sensitive multi-residue indirect competitive enzyme-linked immunosorbent assay for the antibacterial synergists in samples of animal origin

To monitor the abuse of antibacterial synergists, a hapten, trimethoprim carboxylic derivative (TMPCOOH), was designed by using molecular modelling technology. A broad-spectrum monoclonal antibody (mAb) TMP/2G1 was prepared, for which the IC50

Exploring the ability of dihydropyrimidine-5-carboxamide and 5-benzyl-2,4-diaminopyrimidine-based analogues for the selective inhibition of L. major dihydrofolate reductase

To tackle leishmaniasis, search for efficient therapeutic drug targets should be pursued. Dihydrofolate reductase (DHFR) is considered as a key target for the treatment of leishmaniasis. In current study, we are interested in the design and synthesis of selective antifolates targeting DHFR from L. major. We focused on the development of new antifolates based on 3,4-dihydropyrimidine-2-one and 5-(3,5-dimethoxybenzyl)pyrimidine-2,4-diamine motif. Structure activity relationship (SAR) studies were performed on 4-phenyl ring of dihydropyrimidine (26–30) template. While for 5-(3,5-dimethoxybenzyl)pyrimidine-2,4-diamine, the impact of different amino acids (valine, tryptophan, phenylalanine, and glutamic acid) and two carbon linkers were explored (52–59). The synthesized compounds were assayed against LmDHFR. Compound 59 with the IC50 value of 0.10 μM appeared as potent inhibitors of L. major. Selectivity for parasite DHFR over human DHFR was also determined. Derivatives 55–59 demonstrated excellent selectivity for LmDHFR. Highest selectivity for LmDHFR was shown by compounds 56 (SI = 84.5) and 58 (SI = 87.5). Compounds Antileishmanial activity against L. major and L. donovani promastigotes was also performed. To explore the interaction pattern of the synthesized compounds with biological macromolecules, the docking studies were carried out against homology modelled LmDHFR and hDHFR targets.

Photoactivatable trimethoprim-based probes for spatiotemporal control of biological processes

Optogenetic tools allow regulation of cellular processes with light, which can be delivered with spatiotemporal resolution. By combining the chemical versatility of photoremovable protecting groups with the biological specificity of self-labeling tags, we

SMALL MOLECULES FOR DUAL FUNCTION POSITRON EMISSION TOMOGRAPHY (PET) AND CELL SUICIDE SWITCHES

The present invention includes an engineered cell comprising a chimeric antigen receptor (CAR) further comprising a nucleic acid molecule comprising a suicide gene comprising a ligand binding domain and a suicide domain wherein the ligand binding domain is capable of binding to radiolabeled tracer or a small molecule suicide switch. This invention also includes methods for inducing apoptosis of an engineered cell, methods for assessing the efficacy or toxicity of an adoptive cell therapy in a subject, methods for detecting the quantity of engineered T cells in a subject, methods for monitoring an immunotherapy treatment in a subject and methods of imaging engineered T cells in a subject. In some embodiments, the imaging is performed via Positron Emission Topography (PET). This invention further includes a chemical inducer of dimerization (CID), wherein the CID is a Bis-Trimethoprim (Bis-TMP).

Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells

We report the selection of DNA-encoded small molecule libraries against protein targets within the cytosol and on the surface of live cells. The approach relies on generation of a covalent linkage of the DNA to protein targets by affinity labeling. This c

Reversible Control of Protein Localization in Living Cells Using a Photocaged-Photocleavable Chemical Dimerizer

Many dynamic biological processes are regulated by protein-protein interactions and protein localization. Experimental techniques to probe such processes with temporal and spatial precision include photoactivatable proteins and chemically induced dimerization (CID) of proteins. CID has been used to study several cellular events, especially cell signaling networks, which are often reversible. However, chemical dimerizers that can be both rapidly activated and deactivated with high spatiotemporal resolution are currently limited. Herein, we present a novel chemical inducer of protein dimerization that can be rapidly turned on and off using single pulses of light at two orthogonal wavelengths. We demonstrate the utility of this molecule by controlling peroxisome transport and mitotic checkpoint signaling in living cells. Our system highlights and enhances the spatiotemporal control offered by CID. This tool addresses biological questions on subcellular levels by controlling protein-protein interactions.

Amino acid conjugated antimicrobial drugs: Synthesis, lipophilicity- activity relationship, antibacterial and urease inhibition activity

Present work describes the in vitro antibacterial evaluation of some new amino acid conjugated antimicrobial drugs. Structural modification was attempted on the three existing antimicrobial pharmaceuticals namely trimethoprim, metronidazole, isoniazid. Twenty one compounds from seven series of conjugates of these drugs were synthesized by coupling with some selected Boc-protected amino acids. The effect of structural features and lipophilicity on the antibacterial activity was investigated. The synthesized compounds were evaluated against five standard American type culture collection (ATCC) i.e. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi strains of bacteria. Our results identified a close relationship between the lipophilicity and the activity. Triazine skeleton proved beneficial for the increase in hydrophobicity and potency. Compounds with greater hydrophobicity have shown excellent activities against Gram-negative strains of bacteria than Gram-positive. 4-amino unsubstituted trimethoprim-triazine derivative 7b have shown superior activity with MIC = 3.4 μM (2 μg/mL) for S. aureus and 1.1 μM (0.66 μg/mL) for E. coli. The synthesized compounds were also evaluated for their urease inhibition study. Microbial urease from Bacillus pasteurii was chosen for this study. Triazine derivative 7a showed excellent inhibition with IC50 = 6.23 ± 0.09 μM. Docking studies on the crystal structure of B. pasteurii urease (PDB ID 4UBP) were carried out.

Generic Hapten Synthesis, Broad-Specificity Monoclonal Antibodies Preparation, and Ultrasensitive ELISA for Five Antibacterial Synergists in Chicken and Milk

An antibody with broad specificity and principally depending on hapten structure and size is a key reagent for developing a class-selective immunoassay. In the present study, three new generic haptens of antibacterial synergists (ASGs) were proposed using