351002-16-9

Basic information

• Product Name: 4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)-
• Synonyms: 4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)-;9-bromo-7-methyl-2-morpholino-4H-pyrido[1,2-a]pyrimidin-4-one;9-Bromo-7-methyl-2-(4-morpholinyl)-4H-pyrido[1,2-a]pyrimidin-4-one
• CAS NO: 351002-16-9
• Molecular Formula: C₁₃H₁₄BrN₃O₂
• Molecular Weight: 324.17
• Product Categories: Drug Intermediates
• Mol File: 351002-16-9.mol

Chemical Properties

• Boiling Point: 447.3 °C at 760 mmHg
• Flash Point: 224.3 °C
• Appearance: /
• Density: 1.63
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 1.30±0.70(Predicted)
• CAS DataBase Reference: 4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)-(CAS DataBase Reference)
• NIST Chemistry Reference: 4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)-(351002-16-9)
• EPA Substance Registry System: 4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)-(351002-16-9)

Safety Data

• Hazardous Substances Data: 351002-16-9(Hazardous Substances Data)

Usage

Uses

As the provided materials do not specify any particular applications for 4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)-, it is not possible to list specific uses based on the information given. However, given its heterocyclic nature and the presence of functional groups that may interact with biological systems, it can be hypothesized that 4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)- could potentially be used in various applications within the pharmaceutical or chemical industries. These could include:
Used in Pharmaceutical Industry:
4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)could be used as a pharmaceutical intermediate or a lead compound for the development of new drugs, given its potential to interact with biological targets due to its heterocyclic structure and functional groups.
Used in Chemical Research:
In the field of chemical research, 4H-Pyrido[1,2-a]pyrimidin-4-one, 9-bromo-7-methyl-2-(4-morpholinyl)- might serve as a subject for studies exploring the synthesis of novel heterocyclic compounds, their reactivity, and their potential applications in material science or as chemical probes.

Upstream product

• 110-91-8 morpholine 
• 663619-90-7 9-bromo-2-hydroxy-7-methyl-4H-pyrido[1,2-a]pyrimidin-4-one 
• 17282-00-7 3-bromo-5-methylpyridin-2-amine 
• 1173900-34-9 9-bromo-2-hydroxy-7-methyl-4H-pyrido[1,2-a]pyrimidin-4-one hydrochloride 
• 1603-41-4 (5-methyl-pyridin-2-yl)amine 

Downstream Products

• 768401-13-4 MCA₅₂ 
• 1173900-35-0 9-(1-hydroxyethyl)-7-methyl-2-morpholino-4H-pyrido[1,2-a]pyrimidin-4-one 
• 1374310-69-6 C₂₉H₃₈N₄O₄ 
• 1374310-68-5 C₃₉H₅₈N₄O₄ 
• 351071-66-4 7-methyl-2-(4-morpholinyl)-9-{[(1R)-1-phenylethyl]amino}-4H-pyrido[1,2-a]pyrimidin-4-one 
• 1307864-98-7 C₂₄H₂₈N₄O₄ 
• 1307865-00-4 NH₂-SL-TGX 
• 1307864-99-8 C₂₉H₃₉N₅O₄ 

Relevant articles and documents

Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: Synthesis, biological evaluation and molecular modelling

A novel series of TGX-221 analogues was prepared and tested for their potency against the p110α, p110β, and p110δ isoforms of the PI3K enzyme, and in two cellular assays. The biological results were interpreted in terms of a p110β comparative model, in order to account for their selectivity towards this isoform. A CH2NH type linker is proposed to allow binding into the specificity pocket proposed to accommodate the high p110β-selectivity of TGX-221, although there was limited steric tolerance for substituents on the pendant ring with the 2-position most favourable for substitution.

Synthesis of new TGX-221 analogs

TGX-221 is a potent phosphoinositide 3-kinase (PI3K)β inhibitor that has great therapeutic potential to treat prostate cancer. Chemical modification of TGX-221 at positions 2 and 9 was made. Five new TGX-221 analogs with different heterocyclic substituent

Prodrug strategy for PSMA-targeted delivery of TGX-221 to prostate cancer cells

TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit. Recent studies showed that TGX-221 has antiproliferative activity against PTEN-deficient tumor cell lines including prostate cancers. The objective of this study was to develop an encapsulation system for parenterally delivering TGX-221 to the target tissue through a prostate-specific membrane aptamer (PSMAa10) with little or no side effects. In this study, PEG-PCL micelles were formulated to encapsulate the drug, and a prodrug strategy was pursued to improve the stability of the carrier system. Fluorescence imaging studies demonstrated that the cellular uptake of both drug and nanoparticles was significantly improved by targeted micelles in a PSMA positive cell line. The area under the plasma concentration time curve of the micelle formulation in nude mice was 2.27-fold greater than that of the naked drug, and the drug clearance rate was 6.16-fold slower. These findings suggest a novel formulation approach for improving site-specific drug delivery of a molecular-targeted prostate cancer treatment.

Development of a peptide-drug conjugate for prostate cancer therapy

TGX-221 is a highly potent phosphoinositide 3-kinase β (PI3Kβ) inhibitor that holds great promise as a novel chemotherapeutic agent to treat prostate cancer. However, poor solubility and lack of targetability limit its therapeutic applications. The objective of this present study is to develop a peptide-drug conjugate to specifically deliver TGX-221 to HER2 overexpressing prostate cancer cells. Four TGX-221 derivatives with added hydroxyl groups were synthesized for peptide conjugation. Among them, TGX-D1 exhibited a similar bioactivity to TGX-221, and it was selected for conjugation with a peptide promoiety containing a HER2-targeting ligand and a prostate specific antigen (PSA) substrate linkage. From this selection, the peptide-drug conjugate was proven to be gradually cleaved by PSA to release TGX-D1. Cellular uptake of the peptide-drug conjugate was significantly higher in prostate cancer cells compared to the parent drug. Moreover, both the peptide-drug conjugate and its cleaved products demonstrated comparable activities as the parent drug TGX-D1. Our results suggest that this peptide-drug conjugate may provide a promising chemotherapy for prostate cancer patients.

Enantiomerically Pure (-) 2-[1-(7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-A]pyrimidin-9-yl)ethylamino]benzoic Acid, Its Use In Medical Therapy, And A Pharmaceutical Composition Comprising It - 026

The present invention relates to enantiomerically pure (?) 2-[1-(7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)ethylamino]benzoic acid or pharmaceutically acceptable salts thereof, it being in a solid state, its use in medical therapy,

Isoform-specific phosphoinositide 3-kinase inhibitors from an arylmorpholine scaffold

Phosphoinositide 3-kinases (PI3-Ks) are an ubiquitous class of signaling enzymes that regulate diverse cellular processes including growth, differentiation, and motility. Physiological roles of PI3-Ks have traditionally been assigned using two pharmacological inhibitors, LY294002 and wortmannin. Although these compounds are broadly specific for the PI3-K family, they show little selectivity among family members, and the development of isoform-specific inhibitors of these enzymes has been long anticipated. Herein, we prepare compounds from two classes of arylmorpholine PI3-K inhibitors and characterize their specificity against a comprehensive panel of targets within the PI3-K family. We identify multiplex inhibitors that potently inhibit distinct subsets of PI3-K isoforms, including the first selective inhibitor of p110β/p110δ (IC50 p110β = 0.13 μM, p110δ = 0.63 μM). We also identify trends that suggest certain PI3-K isoforms may be more sensitive to potent inhibition by arylmorpholines, thereby guiding future drug design based on this pharmacophore.

INHIBITION OF PHSPHOINOSTIDE 3-DINASE BETA

The present invention relates to selective inhibitors of phosphoinositide (PI) 3-kinase ?, use of the selective inhibitors in anti-thrombotic therapy, and a method for screening compounds useful for the new anti-thrombotic therapy by detecting selective i