21075-86-5

Usage

Uses

Used in Pharmaceutical Industry:
Hydrazinecarboxylic acid, 1-(2-propenyl)-, 1,1-dimethylethyl ester is used as a synthetic intermediate for the creation of new pharmaceuticals. Its unique structure allows for the development of compounds with specific therapeutic properties, contributing to the advancement of medicinal chemistry.
Used in Agrochemical Industry:
In the agrochemical sector, this ester is utilized as a precursor in the synthesis of crop protection products. Its role in formulating effective and targeted agrochemicals underscores its importance in enhancing agricultural productivity and crop protection.
Used in Organic Chemistry Research:
Hydrazinecarboxylic acid, 1-(2-propenyl)-, 1,1-dimethylethyl ester is also employed as a research compound in organic chemistry. It provides a foundation for exploring novel chemical reactions and mechanisms, further expanding the horizons of chemical knowledge and application.

Upstream product

• 34387-89-8 N-(tert-butoxycarbonylamino)phthalimide 
• 870-46-2 t-butoxycarbonylhydrazine 
• 7422-78-8 allylhydrazine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 220294-77-9 N^β,N^β-[bis(tert-butoxycarbonyl)amino]phthalimide 
• 109473-36-1 N-tert-butyloxycarbonylaminoisophthalimide 
• 287729-03-7 tert-butyl (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)prop-2-en-1-ylcarbamate 
• 29518-83-0 S-Methyl-monothiokohlensaeure-tert.-butylester 
• 215655-64-4 1-tert-butyloxycarbonyl-2-(2'-carboxybenzoyl)-hydrazine 

Downstream Products

• 52207-83-7 allylhydrazine dihydrochloride 
• 955368-90-8 2-allyl-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3 ,4-d]pyrimidin-3-one 
• 1226754-63-7 tert-butyl 1-allyl-2-(cyclohexylmethylene)hydrazinecarboxylate 

Relevant academic research and scientific papers

A WEE1 Inhibitor Analog of AZD1775 Maintains Synergy with Cisplatin and Demonstrates Reduced Single-Agent Cytotoxicity in Medulloblastoma Cells

The current treatment for medulloblastoma includes surgical resection, radiation, and cytotoxic chemotherapy. Although this approach has improved survival rates, the high doses of chemotherapy required for clinical efficacy often result in lasting neurocognitive defects and other adverse events. Therefore, the development of chemosensitizing agents that allow dose reductions of cytotoxic agents, limiting their adverse effects but maintaining their clinical efficacy, would be an attractive approach to treat medulloblastoma. We previously identified WEE1 kinase as a new molecular target for medulloblastoma from an integrated genomic analysis of gene expression and a kinome-wide siRNA screen of medulloblastoma cells and tissue. In addition, we demonstrated that WEE1 prevents DNA damage-induced cell death by cisplatin and that the WEE1 inhibitor AZD1775 displays synergistic activity with cisplatin. AZD1775 was developed as a WEE1 inhibitor from an initial hit from a high-throughput screen. However, given the lack of structure-activity data for AZD1775, we developed a small series of analogs to determine the requirements for WEE1 inhibition and further examine the effects of WEE1 inhibition in medulloblastoma. Interestingly, the compounds that inhibited WEE1 in the same nanomolar range as AZD1775 had significantly reduced single-agent cytotoxicity compared with AZD1775 and displayed synergistic activity with cisplatin in medulloblastoma cells. The potent cytotoxicity of AZD1775, unrelated to WEE1 inhibition, may result in dose-limiting toxicities and exacerbate adverse effects; therefore, WEE1 inhibitors that demonstrate low cytotoxicity could be dosed at higher concentrations to chemosensitize the tumor and potentiate the effect of DNA-damaging agents such as cisplatin.

WEE1 Protein degradation agent

WEE1 Protein degradation agents are provided. , The invention provides a compound as shown V, or a pharmaceutically acceptable salt thereof, or a stereoisomer, Y-L-M thereof. WEE1 (V) Wherein M. WEE1 A WEE1 binding moiety capable of binding to WEE1 protein kinase is provided. Y Is E3 ubiquitin ligase ligand moiety, and L Is a linking group.

METHODS OF MAKING WEE1 INHIBITOR COMPOUNDS

The invention relates to a method of producing a WEE1 inhibitor of formula (1A) useful in the treatment of pathological conditions characterized by excessive cell proliferation, such as cancer. In some embodiments, the invention relates to methods for producing intermediate compounds of formulas (3), (5) and (6) as defined in the description.

1,2-DIHYDRO-3H-PYRAZOLO[3,4-D]PYRIMIDINE-3-ONE COMPOUNDS AS INHIBITORS OF WEE-1 KINASE

The disclosure includes compounds of Formula (I) wherein Q, R1, R2, and m are defined herein. Also disclosed is a method for treating a neoplastic disease with these compounds.

WEE1 KINASE INHIBITORS AND METHODS OF TREATING CANCER USING THE SAME

A compound, or a pharmaceutically acceptable salts or prodrugs thereof, having the chemical structure (I) and methods of using these compounds to inhibit WEE1 kinase and treat cancer in a subject.

Development of Potent Pyrazolopyrimidinone-Based WEE1 Inhibitors with Limited Single-Agent Cytotoxicity for Cancer Therapy

WEE1 kinase regulates the G2/M cell-cycle checkpoint, a critical mechanism for DNA repair in cancer cells that can confer resistance to DNA-damaging agents. We previously reported a series of pyrazolopyrimidinones based on AZD1775, a known WEE1 inhibitor, as an initial investigation into the structural requirements for WEE1 inhibition. Our lead inhibitor demonstrated WEE1 inhibition in the same nanomolar range as AZD1775, and potentiated the effects of cisplatin in medulloblastoma cells, but had reduced single-agent cytotoxicity. These results prompted the development of a more comprehensive series of WEE1 inhibitors. Herein we report a series of pyrazolopyrimidinones and identify a more potent WEE1 inhibitor than AZD1775 and additional compounds that demonstrate that WEE1 inhibition can be achieved with reduced single-agent cytotoxicity. These studies support that WEE1 inhibition can be uncoupled from the potent cytotoxic effects observed with AZD1775, and this may have important ramifications in the clinical setting where WEE1 inhibitors are used as chemosensitizers for DNA-targeted chemotherapy.

WEE 1 KINASE INHIBITORS AND METHODS OF MAKING AND USING THE SAME

A compound, or a pharmaceutically acceptable salt thereof, having a chemical structure of formula (I) or formula (II), and methods of using these compounds to treat cancer in an individual.

PYRIDONE-SUBSTITUTED-DIHYDROPYRAZOLOPYRIMIDINONE DERIVATIVE

The invention relates to a compound of general formula (I-0): wherein R1 means a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, or a C3-C6 cycloalkyl group; R2, R3, R4 and R5 mean a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group, or a halo-C1-C6 alkoxy group; R6 means a hydrogen atom, or a C1-C6 alkyl group; R7a means a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group, a hydroxy-C1-C6 alkyl group, -Q2-N(R1c)R1d or a nitrogen-containing heterocyclic group; R8a means a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group or a hydroxy-C1-C6 alkyl group; or R7a and R8a form, as taken together, a C2-C6 alkylene group, or R7a and R8a and the ring atoms to which they bond may form a spiro ring or a bicyclo ring; and X and Y mean a methine group or a nitrogen atom. The compound of the invention has, based on its excellent Wee1 kinase-inhibitory effect, a cell growth-inhibitory effect and an additive/synergistic effect with any other anticancer agent, and is therefore useful in the field of medicine.

Triflimide-catalysed sigmatropic rearrangement of N-allylhydrazones as an example of a traceless bond construction

The recognition of structural elements (that is, retrons) that signal the application of specific chemical transformations is a key cognitive event in the design of synthetic routes to complex molecules. Reactions that produce compounds without an easily identifiable retron, by way of either substantial structural rearrangement or loss of the atoms required for the reaction to proceed, are significantly more difficult to apply during retrosynthetic planning, yet allow for non-traditional pathways that may facilitate efficient acquisition of the target molecule. We have developed a triflimide (Tf 2 NH)-catalysed rearrangement of N-allylhydrazones that allows for the generation of a sigma bond between two unfunctionalized sp 3 carbons in such a way that no clear retron for the reaction remains. This new traceless bond construction displays a broad substrate profile and should open avenues for synthesizing complex molecules using non-traditional disconnections.

Tandem carbon-carbon and carbon-chlorine bond formation by Cu(II) chloride-promoted [3,3] sigmatropic rearrangement of N-allylhydrazones

A new copper(II) chloride-promoted rearrangement of N-allylhydrazones has been developed. Treatment of a number of aromatic N-allylhydrazones with copper(II) chloride provides the formation of both a new carbon-carbon bond and a carbon-chlorine bond in the same reaction. Substrate studies revealed that the carbon-carbon bond-forming step proceeds by way of a concerted [3,3] sigmatropic rearrangement and selectively generates trans-substituted alkenes. Copyright