885698-97-5

Usage

Uses

Used in Pharmaceutical Industry:
2-Chloro-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-methanol is used as a potential drug candidate for various therapeutic applications due to its unique chemical structure and potential interactions with biological receptors or enzymes. Its solubility and stability properties, conferred by the methanol group, may also be advantageous for pharmaceutical formulations.
Used in Drug Development Research:
In the field of drug development, 2-Chloro-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-methanol serves as a subject of study to understand its pharmacological properties and potential mechanisms of action. 2-Chloro-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-methanol's structure and functional groups may provide insights into its interactions with biological targets, which could lead to the discovery of new therapeutic agents.

InChI:InChI=1/C11H12ClN3O2S/c12-11-13-8-5-7(6-16)18-9(8)10(14-11)15-1-3-17-4-2-15/h5,16H,1-4,6H2

Upstream product

• 124773-65-5 (2S)-2-benzyl 1-tert-butyl 5-hydroxypyrrolidine-1,2-dicarboxylate 
• 16233-51-5 1H-thieno[3,2-d]pyrimidine-2,4-dione 
• 16234-14-3 2,4-dichlorothieno[3,2-d]pyrimidine 
• 16234-15-4 2-chloro-4-morpholinothieno[3,2-d]pyrimidine 
• 885618-31-5 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 
• 22288-78-4 Methyl 3-aminothiophene-2-carboxylate 

Downstream Products

• 885698-98-6 4-(6-(bromomethyl)-2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine 
• 955979-15-4 1-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)-N-methylmethanamine 
• 1235450-27-7 Ethyl 2-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methylamino)pyrimidine-5-carboxylate 
• 885675-66-1 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[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 
• 1381841-06-0 4-(2-chloro-6-(chloromethyl)thieno[3,2-d]pyrimidin-4-yl)morpholine 
• 1235451-59-8 ethyl 2-(((2-(3,4-diaminophenyl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)(methyl)amino)pyrimidine-5-carboxylate 
• 1235451-75-8 ethyl 2-(methyl((4-morpholino-2-(1H-pyrrol-3-yl)thieno[3,2-d]pyrimidin-6-yl)methyl)amino)pyrimidine-5-carboxylate 

Relevant academic research and scientific papers

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 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 Dimorpholine Substituted Thienopyrimidines as Potential Class I PI3K/mTOR Dual Inhibitors

Dysfunctional signaling of the PI3K/AKT/mTOR pathway in cancer and its crucial role in cell growth and survival have made it a much desired target for cancer therapeutics. A series of dimorpholine substituted thienopyrimidine derivatives had been prepared and evaluated in vitro and in vivo. Among them, compound 14o was identified as a dual Class I PI3K and mTOR kinase inhibitor, which had an approximately 8-fold improvement in mTOR inhibition relative to the class I PI3K inhibitor 1 (pictilisib, GDC-0941). Western blot analysis confirmed the 14o mechanistic modulation of the cellular PI3K/AKT/mTOR pathway through inhibiting phosphorylation of both AKT and S6 in human cancer cell lines. In addition, 14o demonstrated significant efficacy in SKOV-3 and U87MG tumor xenograft models without causing significant weight loss and toxicity.

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.

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.

Potent and highly selective benzimidazole inhibitors of PI3-kinase delta

Inhibition of PI3Kδ is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective benzimidazole-based inhibitors of PI3Kδ. These inhibitors do not occupy the selectivity pocket between Trp760 and Met752 that is induced by other families of PI3Kδ inhibitors. Instead, the selectivity of the compounds for inhibition of PI3Kδ relative to other PI3K isoforms appears to be due primarily to the strong interactions these inhibitors are able to make with Trp760 in the PI3Kδ binding pocket. The pharmacokinetic properties and the ability of compound 5 to inhibit the function of B-cells in vivo are described.

LIGAND-DIRECTED COVALENT MODIFICATION OF PROTEIN

The present invention relates to enzyme inhibitors. More specifically, the present invention relates to ligand-directed covalent modification of proteins; method of designing same; pharmaceutical formulation of same; and method of use.

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.