35265-88-4

Usage

Uses

Used in Pharmaceutical Research and Drug Development:
Thieno[3,2-d]pyriMidine, 2-chloro-7-Methyl-4-(4-Morpholinyl)is utilized as a key compound in the discovery and development of potential drugs. Its unique structural features and properties make it a valuable candidate for the treatment of various medical conditions, offering a broad scope for therapeutic applications.
Used in the Development of Medications for Specific Medical Conditions:
In the medical and pharmaceutical industry, Thieno[3,2-d]pyriMidine, 2-chloro-7-Methyl-4-(4-Morpholinyl)is employed as a precursor or building block in the synthesis of new medications. Its specific use is driven by the need to address particular health issues, with the aim of enhancing treatment options and improving patient outcomes.

Upstream product

• 110-91-8 morpholine 
• 35265-83-9 2,4-dichloro-7-methyl-thieno[3,2-d]pyrimidine 
• 35265-81-7 7-methylthieno<3,2-d>pyrimidine-2,4-dione 
• 85006-31-1 3-amino-4-methyl-2-thiophenecarboxylic acid methyl ester 

Downstream Products

• 955979-02-9 2-chloro-7-methyl-4-morpholinothieno[3,2-d]-pyrimidine-6-carbaldehyde 
• 1394076-92-6 GNE-317 
• 1394077-00-9 4-(2-chloro-6-(3-methoxyoxetan-3-yl)-7-methylthieno[3,2-d]pyrimidin-4-yl)morpholine 
• 1032757-09-7 (R)-1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one 

Relevant academic research and scientific papers

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.

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.

PROCESS FOR MAKING THIENOPYRIMIDINE COMPOUNDS

Process methods for making the dual mTOR/PI3K inhibitor GDC-0980, named as (S)-1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one, having the structure: and stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof.

Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor

Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modification resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor.

PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND METHODS OF USE

Compounds of Formulas Ia-d where X is S or O, mor is a morpholine group, and R3 is a monocyclic heteroaryl group, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for modulating the activity of lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia-d for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. Formula (Ic) and (Id).