16234-15-4

Basic information

• Product Name: 2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine
• Synonyms: 2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine;2-Chloro-4-(4-morpholinyl)thieno[3,2-d]pyrimidine;4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine;2-chloro-4-(4-Morpholinyl)-;2-chloro-4-Morpholinothieno[3,2-d]pyriMidine;Thieno[3,2-d]pyriMidine, 2-chloro-4-(4-Morpholinyl)-;2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine-4;4-(2-Chlorothieno[3,2-d]pyrimidin-4-yl)
• CAS NO: 16234-15-4
• Molecular Formula: C₁₀H₁₀ClN₃OS
• Molecular Weight: 255.72
• Product Categories: Heterocycle-Pyrimidine series
• Mol File: 16234-15-4.mol

Chemical Properties

• Boiling Point: 393.748 °C at 760 mmHg
• Flash Point: 191.932 °C
• Appearance: /
• Density: 1.463
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.671
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 3.82±0.40(Predicted)
• CAS DataBase Reference: 2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine(16234-15-4)
• EPA Substance Registry System: 2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine(16234-15-4)

Safety Data

• Hazardous Substances Data: 16234-15-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research and Development:
2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine is used as a chemical intermediate for the synthesis of certain drugs or chemical compounds. Its unique structure and reactivity make it a valuable component in the development of new pharmaceutical products.
Used in Chemical Synthesis:
In the field of organic chemistry, 2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine is employed as a key building block in the synthesis of complex molecules. Its presence in the molecular structure can impart specific properties or reactivity that are essential for the desired chemical outcomes.
Used in Academic Research:
2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine is utilized in academic research settings, where scientists and researchers explore its properties, reactivity, and potential applications in various chemical and pharmaceutical processes. 2-Chloro-4-(morpholin-4-yl)thieno[3,2-d]pyrimidine can provide insights into the development of new synthetic pathways and the discovery of novel compounds with potential therapeutic or industrial applications.

InChI:InChI=1/C10H10ClN3OS/c11-10-12-7-1-6-16-8(7)9(13-10)14-2-4-15-5-3-14/h1,6H,2-5H2

Upstream product

• 16233-51-5 2,4-dihydroxythieno[3,2-d]pyrimidine 
• 22288-78-4 Methyl 3-aminothiophene-2-carboxylate 
• 16233-51-5 1H-thieno[3,2-d]pyrimidine-2,4-dione 
• 110-91-8 morpholine 
• 16234-14-3 2,4-dichlorothieno[3,2-d]pyrimidine 

Downstream Products

• 885698-98-6 4-(6-(bromomethyl)-2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine 
• 885675-66-1 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]-pyrimidin-4-yl)morpholine 
• 1235450-27-7 Ethyl 2-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methylamino)pyrimidine-5-carboxylate 
• 1235450-94-8 methyl 2-(((2-(4-(aminomethyl)phenyl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)(methyl)amino)pyrimidine-5-carboxylate 
• 1235450-97-1 methyl 2-(((2-(3-(aminomethyl)phenyl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)(methyl)amino)pyrimidine-5-carboxylate 
• 1235451-07-6 ethyl 2-(((2-(4-aminophenyl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)(methyl)amino)pyrimidine-5-carboxylate 
• 1235450-95-9 ethyl 2-(((2-(4-(acetamidomethyl)phenyl)-4-morpholinothieno[3,2-d]pyrimidine-6-yl)Methyl)(methyl)amino)pyrimidine-5-carboxylate 
• 1235450-96-0 2-(((2-(4-(aminomethyl)phenyl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)(methyl)amino)pyrimidine-5-carboxylic acid 
• 1235450-98-2 ethyl 2-(((2-(3-(acetamidomethyl)phenyl)-4-morpholinothieno[3,2-d]pyrimidine-6-yl)Methyl)(methyl)amino)pyrimidine-5-carboxylate 
• 1235450-99-3 2-(((2-(3-(aminomethyl)phenyl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)(methyl)amino)pyrimidine-5-carboxylic acid 
• 1235451-08-7 ethyl 2-(((2-(4-acetamidophenyl)-4-morpholinothieno-[3,2-d]pyrimidin-6-yl)methyl)(methyl)amino)pyrimidine-5-carboxylate 
• 1146955-36-3 4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine 
• 957054-50-1 4-(2-(1H-indazol-4-yl)-6-((4-(methylsulfonyl)-piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)-morpholine bis-methanesulfonate 

Relevant articles and documents

PARP-1/PI3K double-target inhibitor or pharmaceutically acceptable salt thereof, preparation method and application thereof

The invention discloses a PARP-1/PI3K double-target inhibitor or a pharmaceutically acceptable salt thereof, a preparation method and application thereof. According to the invention, the single active component can play a dual inhibition role on PARP-1 and PI3K, so that the dosage is reduced, the treatment effect is improved, and the toxic and side effects are reduced; and the dual inhibition effect on PARP-1 and PI3K is significant, the IC50 value of each target does not exceed 1.0 [mu]M, and the drug using the PARP-1/PI3K double-target inhibitor as the active component can be used for treating a variety of cancers or tumors related to PARP-1 and/or PI3K.

Discovery of novel and potent PARP/PI3K dual inhibitors for the treatment of cancer

PARP inhibitors have achieved great success in cancers with BRCA mutations, but only a small portion of patients carry BRCA mutations, which results in their narrow indication spectrum. Recently, emerging evidence has demonstrated that combinations of PARP and PI3K inhibitors could evoke unanticipated synergistic effects in various cancers, even including BRCA-proficient ones. In this work, a series of PARP/PI3K dual inhibitors were designed, synthesized, and evaluated for their biological activities. It was found that compounds 9a and 23a exhibited excellent inhibitory activities against PARP-1 (9a: IC50 = 1.57 nM, 23a: IC50 = 0.91 nM) and PI3Kα (9a: IC50 = 2.0 nM, 23a: IC50 = 1.5 nM), and showed promising antiproliferative activities against both BRCA-deficient (HCT-116, HCC-1937) and BRCA-proficient (SW620, MDA-MB-231/468) tumor cells. 9a and 23a also exhibited considerable in vivo antitumor efficacy in an MDA-MB-468 xenograft mouse model, with TGI values of 56.39% and 48.77%, respectively. Additionally, 23a possessed promising profiles including high kinase selectivity and low cardiotoxicity. Overall, this work indicates 9a and 23a might be potential PARP/PI3K dual inhibitors for cancer therapy and deserve further research.

Piperazinone substitute or derivative thereof, preparation method and application thereof, and pharmaceutical composition

The invention relates to a piperazinone substitute or a derivative thereof, a preparation method and application thereof, and a pharmaceutical composition, and belongs to the technical field of anti-tumor drugs. The invention designs a piperazinone substituted heterocyclic small molecule compound. The compound shows good affinity to PI3K delta, and the compound can down-regulate the activity of a PI3K pathway in tumor cells, so that the compound shows good inhibitory activity to PI3K delta dependent tumors, and is expected to be used as one of components of a pharmaceutical preparation for treatment of different tumors. The preparation method of the piperazinone substitute is simple and convenient, and the yield is relatively high.

Design, synthesis and biological evaluation of thieno[3,2-d]pyrimidine derivatives containing aroyl hydrazone or aryl hydrazide moieties for PI3K and mTOR dual inhibition

Recently, PI3K and mTOR have been regarded as promising targets for cancer treatment. Herein, we designed and synthesized four series of novel thieno[3,2-d]pyrimidine derivatives that containing aroyl hydrazone or aryl hydrazide moieties. These derivatives act as PI3K/mTOR dual inhibitors, suggesting that they can be used as cancer therapeutic agents. All compounds were tested for anti-proliferative activity against four cancer cell lines. The structure-activity relationship (SAR) studies were conducted by varying the moieties at the C-6 and C-2 positions of the thieno[3,2-d]pyrimidine core. It indicated that aryl hydrazide at C-6 position and 2-aminopyrimidine at C-2 position are optimal fragments. Compound 18b showed the most potent in vitro activity (PI3Kα IC50 = 0.46 nM, mTOR IC50 = 12 nM), as well as good inhibition against PC-3 (human prostate cancer), HCT-116 (human colorectal cancer), A549 (human lung adenocarcinoma) and MDA-MB-231 (human breast cancer) cell lines. Furthermore, Annexin-V and propidium iodide (PI) double staining confirmed that 18b induces apoptosis in cytotoxic HCT-116 cells. Moreover, the influence of 18b on cell cycle distribution was assessed on the HCT-116 cell line, and a cell cycle arrest was observed at the G1/S phases.

COMBINATION THERAPY WITH A PHOSPHOINOSITIDE 3-KINASE INHIBITOR WITH A ZINC BINDING MOIETY

The invention provides a method of treating cancer in a subject in need thereof, comprising administering to the subject: (a) a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or an acyl group; and (b) a PD-1 signaling inhibitor; wherein the compound of Formula I or pharmaceutically acceptable salt thereof and the PD-1 signaling inhibitor are administered in amounts which in combination are therapeutically effective. The invention further provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, a PD-1 signaling inhibitor and a pharmaceutically acceptable carrier or excipient.

Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents

To develop novel therapeutic agents with anticancer activities, two series of novel 2,4-bismorpholinyl-thieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives were designed, synthesized and evaluated for their biological activities. Among them, compound A12 showed the most potent antitumor activities against HCT116, PC-3, MCF-7, A549 and MDA-MB-231 cell lines with IC50 values of 3.24 μM, 14.37 μM, 7.39 μM, 7.10 μM, and 16.85 μM, respectively. Further explorations in bioactivity were conducted to clarify the anticancer mechanism of compound A12. The results showed that compound A12 obviously inhibited the proliferation of A549 cell lines and decreased mitochondrial membrane potential, which led to the apoptosis of cancer cells and suppressed the migration of tumor cells.

Preparation method of thienopyrimidine compounds and application thereof

The invention relates to thienopyrimidine derivatives as shown in a general formula I, pharmaceutically acceptable salts or prodrugs and a preparation method thereof, which belong to the technical field of medicinal chemistry. In the general formula I, substituent groups L and R2 have meanings given in the specification. The invention also relates to a compound shown in the general formula I, which has a strong effect of inhibiting PI3K. The invention also relates to an application of the compounds and pharmaceutically acceptable salts, solvates or prodrugs thereof in preparation of drugs fortreating and/or preventing diseases caused by abnormal high expression of PI3K, especially the application in preparation of drugs for treating and/or preventing cancers.

Design, synthesis and structure-activity relationship study of piperazinone-containing thieno[3,2-d]pyrimidine derivatives as new PI3Kδ inhibitors

Two classes of piperazinone-containing thieno[3,2-d]pyrimidines were designed and synthesized as new PI3Kδ inhibitors in this study. Detailed SAR study with respect to the piperazinone substituents at the 6-position of thieno[3,2-d]pyrimidine core demonstrated that piperazinone-containing thieno[3,2-d]pyrimidines would be more potent and selective for PI3Kδ than their piperazine counterparts, which led to the discovery of several potent PI3Kδ inhibitors with comparable or better antiproliferative activity against a panel of non-Hodgkin lymphoma (NHL) cell lines as compared with idelalisib. Our study will promote the development of new PI3Kδ inhibitors based on piperazinone-containing thieno[3,2-d]pyrimidine scaffold.

Design, synthesis, and biological evaluation of novel thienopyrimidine derivatives as PI3Kα inhibitors

Three series of novel thienopyrimidine derivatives 9a-l, 15a-l, and 18a-h were designed and synthesized, and their IC50 values against four cancer cell lines HepG-2, A549, PC-3, and MCF-7 were evaluated. Most compounds show moderate cytotoxicity against the tested cancer cell lines. The most promising compound 9a showed moderate activity with IC50 values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32, and 9.80 ± 0.93 μM, respectively. The inhibitory activities of compounds 9a and 15a against PI3Kα and mTOR kinase were further evaluated. Compound 9a exhibited PI3Kα kinase inhibitory activity with IC50 of 9.47 ± 0.63 μM. In addition, docking studies of compounds 9a and 15a were also investigated.

COMPOUNDS AND THERAPEUTIC USES THEREOF

The invention relates to compounds, pharmaceutical compositions and methods useful for treating cancer, systemic or chronic inflammation, rheumatoid arthritis, diabetes, obesity, T-cell mediated autoimmune disease, diseases associated with over production