885675-66-1

Usage

Uses

Used in Pharmaceutical Industry:
2-CHLORO-6-(4-METHANESULFONYL-PIPERAZIN-1-YLMETHYL)-4-MORPHOLIN-4-YL-THIENO[3,2-D]PYRIMIDINE is used as a lead compound for the development of novel pharmaceutical agents targeting specific disease pathways, particularly for conditions that may benefit from its potential anticancer or antiviral properties. Its unique structural features allow for further chemical modifications to optimize its therapeutic efficacy and selectivity.
Used in Medicinal Chemistry Research:
In the realm of medicinal chemistry, 2-CHLORO-6-(4-METHANESULFONYL-PIPERAZIN-1-YLMETHYL)-4-MORPHOLIN-4-YL-THIENO[3,2-D]PYRIMIDINE serves as a valuable template for exploring structure-activity relationships and understanding the molecular mechanisms underlying its biological activities. This knowledge can guide the design of more potent and selective drug candidates with improved pharmacokinetic and safety profiles.
Used in Drug Discovery:
2-CHLORO-6-(4-METHANESULFONYL-PIPERAZIN-1-YLMETHYL)-4-MORPHOLIN-4-YL-THIENO[3,2-D]PYRIMIDINE is utilized in high-throughput screening assays and other drug discovery platforms to identify potential hits and leads with therapeutic potential. Its chemical properties and biological activities make it a suitable candidate for further optimization and development into effective therapeutic agents.
Overall, 2-CHLORO-6-(4-METHANESULFONYL-PIPERAZIN-1-YLMETHYL)-4-MORPHOLIN-4-YL-THIENO[3,2-D]PYRIMIDINE holds great promise in various applications across the pharmaceutical and medicinal chemistry industries, with its potential to contribute to the development of innovative treatments for a range of diseases.

Upstream product

• 885618-31-5 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 
• 161357-89-7 1-(methylsulfonyl)piperazine hydrochloride 
• 55276-43-2 4-methanesulfonylpiperazine 
• 149-73-5 trimethyl orthoformate 
• 1381841-06-0 4-(2-chloro-6-(chloromethyl)thieno[3,2-d]pyrimidin-4-yl)morpholine 
• 885698-97-5 2-chloro-4-morpholinylthiophene[3,2-d]pyrimidine-6-methanol 
• 164331-38-8 tert-butyl 4-(methylsulfonyl)piperazine-1-carboxylate 
• 1416327-30-4 1-((4-(methylsulfonyl)piperazin-1-yl)methyl)-1H-benzotriazole 
• 16234-15-4 2-chloro-4-morpholinothieno[3,2-d]pyrimidine 
• 16234-14-3 2,4-dichlorothieno[3,2-d]pyrimidine 
• 22288-78-4 Methyl 3-aminothiophene-2-carboxylate 
• 16233-51-5 1H-thieno[3,2-d]pyrimidine-2,4-dione 

Downstream Products

• 957054-30-7 pictilisib 
• 956032-81-8 (3-(6-((4-(methanesulfonyl)piperazin-1-yl)methyl)-4-morpholino-thieno[3,2-d]pyrimidin-2-yl)phenyl)methanol 
• 1204033-31-7 4-[6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-2-yl]-phenylamine 
• 1204033-28-2 4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-2-phenylthieno[3,2-d]pyrimidin-4-yl)morpholine 
• 1381841-08-2 C₂₆H₃₃N₇O₄S₂ 
• 1381841-09-3 C₂₇H₃₅N₇O₄S₂ 
• 1381841-10-6 C₂₇H₃₅N₇O₄S₂ 
• 1381841-11-7 C₂₇H₃₇N₇O₄S₂ 
• 1381841-12-8 C₃₁H₄₅N₇O₄S₂ 
• 1381841-15-1 C₂₃H₂₈ClN₇O₄S₂ 
• 1381841-16-2 C₂₃H₂₇Br₂N₇O₄S₂ 
• 1394047-46-1 (E)-4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-(3,4,5-trimethoxybenzylidene)hydrazinyl)thieno[3,2-d]pyrimidin-4-yl)morpholine 
• 1394047-47-2 (E)-4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-(2,3,4-trimethoxybenzylidene)hydrazinyl)thieno[3,2-d]pyrimidin-4-yl)morpholine 
• 1394047-53-0 (E)-4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-(4-(trifluoromethoxy)benzylidene)hydrazinyl)thieno[3,2-d]-pyrimidin-4-yl)morpholine 

Relevant academic research and scientific papers

Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents for the treatment of hematopoietic malignancies

Combinations of PI3K inhibitor compounds having Formula I and chemotherapeutic agents, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for treating hematopoietic malignancies. Methods of using such combinations for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed

Phosphoinositides 3-serinekinase inhibitor compd. antialopecic agent and combinations, and method of use

Combinations of PI3K inhibitor compounds having Formulas I and II and chemotherapeutic agents, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for treating hyperproliferative disorders such as cancer. Methods of using such combinations for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

PHOSPHOINOSITIDE 3-KINASE INHIBITORS WITH ZINC BINDING MOIETY

PROBLEM TO BE SOLVED: To provide phosphoinositide 3-kinase inhibitors with a zinc binding moiety. SOLUTION: There is provided a compound represented by formula (I) in the figure. (X is S, O or the like; Y is CH, N or the like; G1 is optionally substituted N or the like; R1 and R2 are each independently H or the like; C is a substituted heterocycle or the like; B is a linear alkyl or the like; Ra and Rb together with the nitrogen atom coupled to them are morpholino or the like; G2 is an indazole ring or the like; q, r and s are independently from 0 to 1, provided that at least one of them is 1; t is from 0 to 1; n is from 0 to 4; and p is from 0 to 2.) COPYRIGHT: (C)2016,JPOandINPIT

TREATMENT OF CANCERS HAVING K-RAS MUTATIONS

The present invention provides a method of treating a cancer associated with a K-ras mutation in a subject in need thereof. The method comprises the steps of: (1) identifying a subject with a cancer associated with a K-ras mutation; and (2) administering to the subject (i) an inhibitor of PI3 kinase and (ii) an HDAC inhibitor, wherein the PI3 kinase inhibitor and the HDAC inhibitor are administered in amounts which together are therapeutically effective.

A practical synthesis of a PI3K inhibitor under noncryogenic conditions via functionalization of a lithium triarylmagnesiate intermediate

We report a practical synthesis of PI3K inhibitor GDC-0941. The synthesis was achieved using a convergent approach starting from a thienopyrimidine intermediate through a sequence of formylation and reductive amination followed by Suzuki-Miyaura cross-coupling. Metalation of the thienopyrimidine intermediate involving the intermediacy of triarylmagnesiates allowed formylation under noncryogenic conditions to produce the corresponding aldehyde. We also investigated aminoalkylation via a benzotriazolyl-piperazine substrate as an alternative to the reductive amination route. We evaluated both palladium and nickel catalyzed processes for the borylation and Suzuki-Miyaura cross-coupling. Final deprotection and salt formation afforded the API.

Synthesis and cytotoxic activity of novel 2,6-disubstituted-4-mor- pholinothieno[3,2-d]pyrimidines as potent anti-tumor agents

A series of 2,6-disubstituted-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and their cytotoxic activity against H460, HT-29, MDA-MB-231, U87MG and H1975 cancer cell lines were evaluated in vitro. Most of the target compounds exhibited moderate to excellent activity to the tested cell lines. The most promising compound 23 (0.84 μmol/L, 0.23 μmol/L, 2.52 μmol/L, 1.80 μmol/L) was 1.0, 2.9, 29.3 and 4.3 times more active than GDC-0941 (0.87 μmol/L, 0.66 μmol/L, 73.8 μmol/L, 7.77 μmol/L) against H460, HT-29, MDA-MB-231 and U87MG cell lines, respectively.

Design, synthesis and anticancer activity of 4-morpholinothieno[3,2-d]- pyrimidine derivatives bearing arylmethylene hydrazine moiety

Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC50 values of 0.003 μM, 0.42 μM and 0.74 μM, which was 1.6- to 290-fold more potent than GDC-0941.

TREATMENT OF CANCERS HAVING K-RAS MUTATIONS

The present invention provides a method of treating a cancer associated with a K- ras mutation in a subject in need thereof. The method comprises the steps of (1) identifying a subject with a cancer associated with a K-ras mutation; and (2) adminsiterign to the subject (i) an inhibitor of PI3 kinase and (ii) an HDAC inhibitor, wherein the PI3 kinase inhibitor and the HDAC inhibitor are administered in amounts which together are therapeutically effective.

COMBINATIONS OF PHOSPHOINOSITIDE 3-KINASE INHIBITOR COMPOUNDS AND CHEMOTHERAPEUTIC AGENTS FOR THE TREATMENT OF HEMATOPOIETIC MALIGNANCIES

Combinations of PI3K inhibitor compounds having Formula I and chemotherapeutic agents, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for treating hematopoietic malignancies. Methods of using such combinations for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

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.