86770-31-2

Basic information

• Product Name: 3,5-Dimethylpyrrole-2,4-dicarboxylic acid 2-t-butyl ester-4-ethyl ester
• Synonyms: 3,5-dimethylpyrrole-2,4-dicarboxylic acid 2-t-butyl ester-4-ethyl ester;3,5-DIMETHYLPYRROLE-2,4-DICARBOXYLIC ACID 4-ETHYL ESTER-2-T-BUTYL ESTER;3,5-DIMETHYLPYRROLE-2,4-DICARBOXYLIC ACID 4-ETHYL ESTER-2-TERT-BUTYL ESTER;3,5-DIMETHYL-1H-PYRROLE-2,4-DICARBOXYLIC ACID-2-BUTYL-4-ETHYL ESTER;3,5-DIMETHYL-1H-PYRROLE-2,4-DICARBOXYLIC ACID 2-TERT-BUTYL ESTER 4-ETHYL ESTER;2-TERT-BUTYL 4-ETHYL 3,5-DIMETHYL-1H-PYRROLE-2,4-DICARBOXYLATE;SALOR-INT L157929-1EA;2-tert-Butyl 4-ethyl 3,5-dimethylpyrrole-2,4-dicarboxylate
• CAS NO: 86770-31-2
• Molecular Formula: C₁₄H₂₁NO₄
• Molecular Weight: 267.32
• EINECS: 1806241-263-5
• Product Categories: HANTZSCH;Pharmaceutial intermediates;Imidazoles, Pyrroles, Pyrazoles, Pyrrolidines;Organic acids;API intermediates;Intermediate of sunitinib malate
• Mol File: 86770-31-2.mol

Chemical Properties

• Boiling Point: 386.8 °C at 760 mmHg
• Flash Point: 187.8 °C
• Appearance: /
• Density: 1.103 g/cm³
• Vapor Pressure: 3.44E-06mmHg at 25°C
• Refractive Index: 1.509
• Storage Temp.: 2-8°C
• PKA: 14.56±0.50(Predicted)
• CAS DataBase Reference: 3,5-Dimethylpyrrole-2,4-dicarboxylic acid 2-t-butyl ester-4-ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Dimethylpyrrole-2,4-dicarboxylic acid 2-t-butyl ester-4-ethyl ester(86770-31-2)
• EPA Substance Registry System: 3,5-Dimethylpyrrole-2,4-dicarboxylic acid 2-t-butyl ester-4-ethyl ester(86770-31-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 86770-31-2(Hazardous Substances Data)

Usage

InChI:InChI=1/C14H21NO4/c1-7-18-12(16)10-8(2)11(15-9(10)3)13(17)19-14(4,5)6/h15H,7H2,1-6H3

Upstream product

• 1694-31-1 tert-butyl acetoacetate 
• 79232-64-7 (Z)-2-hydroxyimino-3-oxo-butyric acid tert-butyl ester 
• 141-97-9 ethyl acetoacetate 
• 14352-65-9 t-butyl 2-hydroxyimino-3-oxobutanoate 
• 1312786-80-3 tert-butyl (E)-2-(hydroxyimino)-3-oxobutanoate 

Downstream Products

• 6314-22-3 5-acetyl-2,4-dimethyl-pyrrole-3-carboxylic acid ethyl ester 
• 2199-51-1 2,4-dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester 
• 2199-59-9 ethyl (5-formyl-2,4-dimethyl-1H-pyrrole)-3-carboxylate 
• 517894-64-3 5-formyl-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 
• 67087-19-8 tri(2,4-dimethyl-3-carbethoxypyrrolyl)methane 
• 2407-87-6 bis(2,4-dimethyl-3-carbethoxypyrrolyl)methene 
• 356068-86-5 N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide 
• 5442-91-1 3,5-dimethyl-1H-pyrrole-2,4-dicarboxylic acid 4-ethyl ester 
• 341031-54-7 sunitinib malate 

Relevant articles and documents

Antimicrobial and antiproliferative study of chalcone clubbed 2,4-dimethylpyrrole-3-carboxamide derivatives: Synthesis and in vitro evaluation

The presented study explores the anticancer potency of a novel series of chalcone clubbed 2,4-dimethyl-1H-pyrrole-3-carboxamide derivatives. In vitro antimicrobial screening concluded that five compounds are potential against Candida albicans having inhibition of growth in the range of 46.38%–73.05% against at the concentration of 32 μg/mL. The antiproliferative screening against 60 cancer cell lines revealed that seven compounds have great potential against the various types of cancer cell lines with inhibition of growth in the range of 41%–71%. The structure–activity relationship study concluded that the hydrazide bond is more significant than the carboxamide bond. In silico study of highly potential derivatives obeys each parameter of Lipinski rule of five and qualified drug-likeness behavior. The presented pyrrole-chalcone template delivered various candidates as anticancer agents, and those could be a potential scaffold to develop the new anticancer drug.

Low-cost clean method for preparing 2,4-dimethyl pyrrole-3,5-dicarboxylate

The invention discloses a low-cost clean method for preparing 2,4-dimethyl pyrrole-3,5-dicarboxylate. The method comprises the following steps: mixing ethyl acetoacetate or tert-butyl acetoacetate with glacial acetic acid, slowly introducing inert gas into the mixed solution for 30 minutes, then introducing a nitrosation reagent nitric oxide gas at the flow rate of 0.5-1mL/min, conducting reacting at room temperature for 10 hours, controlling the temperature of the reaction solution to be 40 DEG C or lower, adding zinc powder in batches, dropwise adding ethyl acetoacetate at the same time, conducting reacting at 95 DEG C for 4 hours, conducting cooling, adding a reaction solution into ice water, conducting filtering, recrystallizing a filter cake with ethanol to obtain white ethyl 2,4-dimethyl pyrrole-3,5-dicarboxylate, and concentrating a filtrate to recover zinc acetate and acetic acid so as to realize the cleanness of the preparation process.

Synthesis, biological evaluation, and in silico study of pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid derivatives

A potential molecular hybridization strategy was used to develop 24 novel pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid and amide derivatives. The preliminary in vitro antimicrobial assay delivered four potential derivatives with growth inhibition in the range of 50.87–56.60% at the concentration of 32 μg/ml. In the search of an anticancer candidate, all derivatives were screened by NCI-60 at 10 μM concentration, revealing that 12 derivatives were potential agents against the various types of cancer cell lines, with growth inhibition in the range of 50.21–108.37%. The in vitro cytotoxicity assay against the cell line HEK293 (human embryonic kidney cells) and the hemolysis assay of the representative potent compounds propose their potential for a good therapeutic index. In silico studies of the most potent derivatives qualified their significant pharmacokinetic properties with good predicted oral bioavailability and their adherence to Lipinski's rule of five for druglikeness. A molecular docking study against VEGFR-2 with the best-scored conformations reinforced their anticancer potency. The docking study of the most potent compound against VEGFR-2 with the best-scored conformations displayed a binding affinity (?9.5 kcal/mol) comparable with the drug sunitinib (?9.9 kcal/mol) and exhibited that tighter interactions at the active adenosine triphosphate site might be responsible for anticancer potency.

Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

Zeste enhancer homolog 2 (EZH2) is highly expressed in various malignant tumors, which could silence tumor suppressor genes via trimethylation of H3K27. Herein was first reported a novel series of pyrrole-3-carboxamide derivatives carrying a pyridone fragment as EZH2 inhibitors. By combining computational modeling, in vitro cellular assays and further rational structure-activity relationship exploration and optimization, compound DM-01 showed powerful inhibition towards EZH2. DM-01 was found to have significant ability to reduce the cellular H3K27me3 level in K562 cells in the Western blot test. Meanwhile, our data showed that knockdown EZH2 in A549 cells resulted in a decrease of cell sensitivity to DM-01 at 50 and 100 μM. DM-01 could also increase the transcription expression of DIRAS3 in a dose-dependent manner, a tumor suppressor in the downstream of EZH2, suggesting it was worth investigating further as a lead compound.

Novel RIP1 kinase inhibitor containing pyrrole ring and indoline structure and application thereof

The invention relates to a novel RIP1 kinase inhibitor containing a pyrrole ring and an indoline structure and application in preparing drugs for treating inflammation, ischemic diseases and cell injury type diseases.

Development of a novel conjugatable sunitinib analogue validated through in vitro and in vivo preclinical settings

Sunitinib is an oral FDA/EMEA approved multi-targeted tyrosine kinase inhibitor. It possesses anti-angiogenic and antitumor activity against a variety of advanced solid tumors. However, its chemical core does not allow a potential linkage to tumor-homing elements that could eventually enhance its potency. Therefore, a novel linkable sunitinib derivative, designated SB1, was rationally designed and synthesized. The pharmaceutical profile of SB1 was explored both in vitro and in vivo. Mass spectrometry and NMR spectroscopy were utilized for characterization, while MTT assays and LC-MS/MS validated protocols were used to explore its antiproliferative effect and stability, respectively. Cytotoxicity evaluation in three glioma cells showed that SB1 preserved the antiproliferative effect of sunitinib. SB1 was stable in vitro after 24 h incubation in mouse plasma, while both agents exhibited bioequivalent pharmacokinetic characteristics after i.v. administration in Balb/c mice. To evaluate the levels of SB1 in mouse plasma, a novel analytical method was developed and validated in accordance to the US FDA and the EU EMA guidelines. We formulated a novel linkable sunitinib analog exhibiting similar antiproliferative and apoptotic properties with native sunitinib in glioma cell lines. Both SB1 and native sunitinib showed identical in vitro stability in mouse plasma and pharmacokinetics after i.v. administration in Balb/c mice.

5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: Design, synthesis and cytotoxicity against cancer cells

Angiogenesis plays important roles in tumor growth and metastasis. Sunitinib (Sutent) is an antitumor agent targeting receptor tyrosine kinases which are involved in angiogenesis as well as cancer cell growth and survival. Using the pyridin-3-ol scaffold, which was previously reported as an excellent antioxidant and antiangiogenic platform, we have synthesized sunitinib mimics 6 by hybridizing bicyclic pyridinol 4 as a key scaffold and pyrrole-2-carbaldehydes 7 as side chains. Cytotoxicity assays showed that compounds 6 have comparable to better anticancer activity than sunitinib against five different cancer cell lines. In addition, compounds 6 showed even lower levels of cytotoxicity against normal cells, resulting in up to 26-fold better safety windows, than sunitinib. Signaling pathway-associated transcription factor reporter assay and western blot analyses revealed that apoptosis induction in MDA-MB-231 human breast cancer cells by 6F is mainly mediated through the p53 increase and down-regulation of phospho-signal transducer and activator of transcription 3 (STAT3) and its target gene products, cyclin D, Bcl-2, and survivin. The data strongly suggest that our hybrid compounds can provide a novel anticancer scaffold with improved and safer cytotoxicity profiles than sunitinib.

Synthesis and in vitro antitumor activity of 1-(3-dimethylamino)propyl indolin-2-one derivatives

A series of 1-(3-dimethylaminopropyl)indolin-2-one derivatives were designed and synthesized based on the structural features of TMP-20, LK-B030, and BX-517. These newly synthesized derivatives were evaluated for in vitro activity against five human cancer cell lines and three HUVECs. Results revealed that all of the target compounds 1a-h generally show potent activity against these cancer cell lines and higher selectivity on VEGF- and bFGF-stimulated HUVECs than HUVEC. In particular, 1f (IC50s: 1.10-1.47 μM) is 1.8-6.0-fold more potent than sunitinib against MDA-MB-231, A549, HL-60 and K-562, and 1.6-2.8-fold more potent than LK-B030 against MDA-MB-231 and A549.

COMPOSITIONS AND METHODS FOR TREATMENT OF NEURODEGENERATIVE DISEASE

Compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed.

Synthesis and antitumor activity of 5-[1-(3-(dimethylamino)propyl)-5- halogenated-2-oxoindolin-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3- carboxamides

We report herein the design and synthesis of novel 1-[3-(dimethylamino) propyl]indolin-2-one derivatives based on the structural features of Sunitinib, a known multitargeted receptor tyrosine kinase inhibitor, and TMP-20, a previously discovered compound with good antitumor activity in our lab. These newly synthesized derivatives were evaluated for in vitro activity against five human cancer cell lines and VEGF/bFGF-stimulated HUVECs. Results revealed that all of the target compounds 1a-p show potent antitumor activity, compounds 1e-h (IC50's: 0.45-5.08 μM) are more active than Sunitinib (IC 50's: 1.35-6.61 μM), and the most active compound 1h (IC 50: 0.47-3.11 μM) is 2.1-4.6-fold more potent than Sunitinib against all five cancer cell lines. In addition, like Sunitinib, 1a-p have higher selectivity on VEGF-stimulated HUVEC other than bFGF-stimulated HUVEC.