714273-83-3

Basic information

• Product Name: 1H-Imidazole-4-carboxaldehyde, 5-(1,1-dimethylethyl)- (9CI)
• Synonyms: 1H-Imidazole-4-carboxaldehyde, 5-(1,1-dimethylethyl)- (9CI);4-tert-butyl-1H-iMidazole-5-carbaldehyde;1H-IMidazole-4-carboxaldehyde, 5-(1,1-diMethylethyl)-;5-(1,1-Dimethylethyl)-1H-imidazole-4-carboxaldehyde;1H-Imidazole-5-carboxaldehyde, 4-(1,1-dimethylethyl)-;1H-Imidazole-4-carbaldehyde,5-(1,1-dimethylethyl)-;EOS-62086
• CAS NO: 714273-83-3
• Molecular Formula: C₈H₁₂N₂O
• Molecular Weight: 152.19368
• EINECS: 202-303-5
• Product Categories: ALDEHYDE
• Mol File: 714273-83-3.mol

Chemical Properties

• Boiling Point: 338.876 °C at 760 mmHg
• Flash Point: 162.978 °C
• Appearance: /
• Density: 1.092 g/cm³
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 11.53±0.10(Predicted)
• CAS DataBase Reference: 1H-Imidazole-4-carboxaldehyde, 5-(1,1-dimethylethyl)- (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-Imidazole-4-carboxaldehyde, 5-(1,1-dimethylethyl)- (9CI)(714273-83-3)
• EPA Substance Registry System: 1H-Imidazole-4-carboxaldehyde, 5-(1,1-dimethylethyl)- (9CI)(714273-83-3)

Safety Data

• Hazardous Substances Data: 714273-83-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1H-Imidazole-4-carboxaldehyde, 5-(1,1-dimethylethyl)(9CI) is utilized as a key intermediate in the synthesis of various pharmaceuticals. Its unique structure allows for the development of compounds with specific therapeutic properties, contributing to the creation of new drugs for treating a range of medical conditions.
Used in Agricultural Chemical Industry:
In the agricultural sector, 1H-Imidazole-4-carboxaldehyde, 5-(1,1-dimethylethyl)- (9CI) serves as a building block for the synthesis of agricultural chemicals. Its incorporation into these products can enhance their effectiveness in pest control and crop protection, thereby supporting sustainable agricultural practices.
Used in Organic Synthesis:
1H-Imidazole-4-carboxaldehyde, 5-(1,1-dimethylethyl)(9CI) is employed as a versatile intermediate in organic synthesis across various industries. Its structural features facilitate the production of a broad spectrum of organic compounds, including those with applications in materials science, specialty chemicals, and other advanced technologies.

Upstream product

• 1538-75-6 2,2-dimethylpropanoic anhydride 
• 5469-26-1 1-Bromopinacolon 
• 51721-22-3 (5-(tert-butyl)-1H-imidazol-4-yl)methanol 
• 51721-21-2 5-(tert-butyl)-1H-imidazole-4-carboxylic acid ethyl ester 
• 714273-89-9 5-(tert-butyl)oxazole-4-carboxylic acid ethyl ester 
• 29509-07-7 2-chloro-4,4-dimethyl-3-oxopentanoic acid ethyl ester 
• 51721-21-2 ethyl 4-(tert-butyl)-1H-imidazole-5-carboxylate 
• 17094-34-7 ethyl pivaloylacetate 
• 51721-22-3 (4-(tert-butyl)-1H-imidazol-5-yl)methanol 

Downstream Products

• 714272-27-2 (3Z,6Z)-3-[[5-(1,1-dimethylethyl)-1H-imidazol-4-yl]methylene]-6-(phenylmethylene)piperazine-2,5-dione 
• 1367709-16-7 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-phenylmethylidene]-2,5-piperazinedione trifluoroacetate 
• 714272-29-4 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(2-methoxyphenyl)methylidene]-2,5-piperazinedione 
• 1367717-84-7 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(3-methoxyphenyl)methylidene]-2,5-piperazinedione trifluoroacetate 
• 714272-28-3 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(4-methoxyphenyl)methylidene]-2,5-piperazinedione 
• 714272-36-3 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(2,3-dimethoxyphenyl)methyllidene]-2,5-piperazinedione trifluoroacetate 
• 714272-33-0 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(2,4-dimethoxyphenyl)methylidene]-2,5-piperazinedione 
• 1367720-57-7 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(2,5-dimethoxyphenyl)methylidene]-2,5-piperazinedione trifluoroacetate 
• 714272-34-1 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(3,4-dimethoxyphenyl)methylidene]-2,5-piperazinedione 
• 714272-83-0 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(3-methylphenyl)methylidene]-2,5-piperazinedione trifluoroacetate 
• 714272-81-8 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(2-fluorophenyl)methylidene]-2,5-piperazinedione trifluoroacetate 
• 714272-77-2 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(3-fluorophenyl)methylidene]-2,5-piperazinedione trifluoroacetate 
• 714272-75-0 3-{(Z)-1-[5-(tert-butyl)-1H-4-imidazolyl]methylidene}-6-[(Z)-1-(4-fluorophenyl)methylidene]-2,5-piperazinedione trifluoroacetate 
• 714273-67-3 (3Z,6Z)-3-((5-tert-butyl-1H-imidazol-4-yl)methylene)-6-(2,5-difluorobenzylidene)piperazine-2,5-dione trifluoroacetate 

Relevant articles and documents

Preparation method of plinabulin intermediate imidazole formaldehyde compound

The invention discloses a preparation method of an imidazole formaldehyde compound. According to the preparation method, the operation danger level and the production cost are reduced by optimizing and improving a preparation route method, optimizing reaction conditions and improving a post-treatment and purification method; the requirement on the corrosion resistance grade of reaction container equipment is low, the operation safety is good, and the post-treatment is green and environment-friendly; and the preparation method has the advantages of simple operation of each step, safe and feasible solvent and process conditions, realization of environment-friendly production, and wide application prospect.

Structure-based design and synthesis of novel furan-diketopiperazine-type derivatives as potent microtubule inhibitors for treating cancer

Plinabulin, a synthetic analog of the marine natural product “diketopiperazine phenylahistin,” displayed depolymerization effects on microtubules and targeted the colchicine site, which has been moved into phase III clinical trials for the treatment of non-small cell lung cancer (NSCLC) and the prevention of chemotherapy-induced neutropenia (CIN). To develop more potent anti-microtubule and cytotoxic derivatives, the co-crystal complexes of plinabulin derivatives were summarized and analyzed. We performed further modifications of the tert-butyl moiety or C-ring of imidazole-type derivatives to build a library of molecules through the introduction of different groups for novel skeletons. Our structure–activity relationship study indicated that compounds 17o (IC50 = 14.0 nM, NCI-H460) and 17p (IC50 = 2.9 nM, NCI-H460) with furan groups exhibited potent cytotoxic activities at the nanomolar level against various human cancer cell lines. In particular, the 5-methyl or methoxymethyl substituent of furan group could replace the alkyl group of imidazole at the 5-position to maintain cytotoxic activity, contradicting previous reports that the tert-butyl moiety at the 5-position of imidazole was essential for the activity of such compounds. Immunofluorescence assay indicated that compounds 17o and 17p could efficiently inhibit microtubule polymerization. Overall, the novel furan-diketopiperazine-type derivatives could be considered as a potential scaffold for the development of anti-cancer drugs.

Development of MBRI-001, a deuterium-substituted plinabulin derivative as a potent anti-cancer agent

Plinabulin, a drug targeting microtubule of cancer cells, has been currently tried in its phase III clinical study. However, low efficacy caused by poor pharmacokinetic (PK) properties has been considered to be the main obstacle to approved by the Food and Drug Administration. Herein, we introduced a deuterium atom as an isostere in its structure to become a new compound named (MBRI-001, No. 9 in a series of deuterium-substituted compounds). The structure of MBRI-001 was characterized by HRMS, NMR, IR and a single crystal analysis. MBRI-001 exhibited better pharmacokinetic characteristics than that of plinabulin. Additionally, its antitumor activity is in a low nanomolar level for a variety of cancer cell lines and high activity against human NCI-H460 xenograted in mice intravenous administration. Importantly, continuous administration of MBRI-001 exhibited lower toxicity compared to docetaxel. We thus suggest that MBRI-001 could be developed as a promising anti-cancer agent in near future.

Plinabulin compound polycrystalline type and preparation method thereof

The invention provides a plinabulin compound polycrystalline type and a preparation method thereof, and particularly relates to a polycrystalline type of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone and a preparation method thereof. Three kinds of crystalline types beta, gamma and delta are developed on the basis of the crystalline type alpha of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone, wherein the three kinds of crystalline types beta, gamma and delta can be prepared into monocrystallines; the three kinds of crystalline types have the advantages of clear conformation, high purity and high method repeatability; the important significance is realized on implementation of plinabulin biological effectiveness study and dosage form variety development.

Preparation and purification method of high-purity Plinabulin compound

The invention provides a preparation and purification method of high-purity Plinabulin compound, which aims at mainly removing a trans-isomer. The preparation and purification method has the advantages that (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)methylene)piperazine-2,5-diketone monohydrate and (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)deuterated methylene)piperazine-2,5-diketone monohydrate are prepared; the purity of the prepared product is higher than 99.5%, and the content of the trans-isomer is smaller than 0.1%. The invention also relates to the preparation and purification of important intermediates, such as 5-(tert-butyl)-1H-imidazole-4-ethyl formate and 1,4-diacetylpiperazine-2,5-diketone. The preparation and purification method has the advantages that the production cost is reduced, the pos-treatment difficulty is decreased, and the technology more meets the requirements of industrialized production.

Ferrocenyl 2,5-Piperazinediones as Tubulin-Binding Organometallic ABCB1 and ABCG2 Inhibitors Active against MDR Cells

The tubulin-microtubule system is a common target of many anticancer drugs. However, the use of chemotherapeutics frequently leads to the development of a clinically relevant phenomenon of multidrug resistance (MDR). One of the basic mechanisms involved in MDR involves elevated expression and/or activity of several ATP-binding cassette superfamily members (ABC transporters) which are normally responsible for the efflux of xenobiotics or secondary metabolites outside the cell. Here we present the synthesis and biological characteristics of ferrocenyl analogues of plinabulin, i.e. one of the so-called "spindle poisons". We found that replacement of the phenyl group of plinabulin by the ferrocenyl moiety turns this compound into a potent inhibitor of ABCB1 and ABCG2, thus making it possible to overcome the multidrug resistance phenomenon. We also demonstrated that the alkyl group attached to the imidazole moiety of ferrocenyl analogues of plinabulin strongly affects their potency to inhibit tubulin polymerization.

Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus

We previously reported potent hit compound 4 inhibiting the wild-type influenza A virus A/HK/68 (H3N2) and A/M2-S31N mutant viruses A/WS/33 (H1N1), with its latter activity quite weak. To further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. Several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. Among them, 33 was the most potent compound, which was identified as being active on an amantadine-sensitive virus through blocking of the viral M2 ion channel. Furthermore, 33 markedly inhibited the amantadine-resistant virus (IC50 = 3.4 μM) and its activity increased by almost 24-fold compared to initial compound, with its action mechanism being not M2 channel mediated.

Synthesis and structure-activity relationship study of antimicrotubule agents phenylahistin derivatives with a didehydropiperazine-2,5-dione structure

Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities. In the SAR study, we developed more potent derivatives 33 with 2,5-difluorophenyl and 50 with a benzophenone in place of the phenyl group. The anti-HuVEC activity of 33 and 50 exhibited a lowest effective concentration of 2 and 1 nM for microtubule depolymerization, respectively. The values of 33 and 50 were 5 and 10 times more potent than that of CA-4, respectively. These derivatives could be a valuable second-generation derivative with both vascular disrupting and cytotoxic activities.

ANALOGS OF DEHYDROPHENYLAHISTINS

Analogs of dehydrophenylahistins are disclosed as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.

ANALOGS OF DEHYDROPHENYLAHISTINS AND THEIR THEAPEUTIC USE

Compounds represented by the following structure (II) are disclosed: as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.