The application of disubstituted vinylogous iminium salts and related synthons to the regiocontrolled preparation of unsymmetrical 2,3,4-trisubstituted pyrroles

Gupton, John T.; Krumpe, Keith E.; Burnham, Bruce S.; Dwornik, Kate A.; Petrich, Scott A.; Du, Karen; Bruce, Marc A.; Vu, P.; Vargas, Marian; Keertikar, Kartik M.; Hosein, Kirsten N.; Jones, Claude R.; Sikorski, James A.

doi:10.1016/s0040-4020(98)00247-6

Cited by 51 publications

(25 citation statements)

References 11 publications

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“…In the human Tmolt 3 leukemia screen compounds 8 and 9 produced ED 50 values of 1.85 and 1.58 µg/ml, respectively. Only compounds 9 and 11 demonstrated good activity in the Tmolt 4 leukemia screen with values of 1.5 µg/ml and 2.85 µg/ml, respectively. All of the compounds were active against the growth of human Hl-60 leukemia growth with compounds 2-6, 8, and 11 being the most active.…”

Section: Resultsmentioning

confidence: 99%

“…The starting materials (2,4-disubstituted pyrroles) used in the following procedures have been previously reported [1][2][3][4] . All purified compounds gave a single spot upon TLC analysis on silica gel 7GF with an ethyl acetate/hexane mixture [30/70] as eluent.…”

Section: Materials and Apparatusmentioning

confidence: 99%

“…Previously, we have described the regiochemically controlled synthesis of a variety of highly functionalized pyrroles [1][2][3][4] which are structurally related to a number of bioactive marine natural products [5,6] . We have recently reported the cytotoxicity of some of these derivatives in murine and human tumor cultured cells [7] including suspended as well as selected solid tumors.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Cytotoxicity of 2,4-Disubstituted and 2,3,4-Trisubstituted Brominated Pyrroles in Murine and Human Cultured Tumor Cells

Gupton

Burham

Krumpe

et al. 2000

Arch. Pharm. Pharm. Med. Chem.

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Section: Resultsmentioning

confidence: 99%

Section: Materials and Apparatusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and Cytotoxicity of 2,4-Disubstituted and 2,3,4-Trisubstituted Brominated Pyrroles in Murine and Human Cultured Tumor Cells

Gupton

Burham

Krumpe

et al. 2000

Arch. Pharm. Pharm. Med. Chem.

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“…The regioselective synthesis of 2,3,4-trisubstituted pyrroles from chloroenals has recently been reported by Gupton, et. al [1][2][3][4]32,33]. The convergent synthesis generates acceptable yields through the final condensation, however with the aid of the XT reactor (Mettler-Toledo AutoChem), up to six derivatives were easily prepared under a dry, inert atmosphere and constant temperature.…”

Section: Chemistrymentioning

confidence: 99%

Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

et al. 2004

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-A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent hypolipidemic agents lowering serum triglyceride concentrations in CF-1 male mice after 14 days of I.P. administration. One agent orally lowered serum cholesterol in Sprague-Dawley male rats at 2mg/kg/day after 14 days. The agents demonstrated a lowering of mouse serum LDLcholesterol levels and selected compounds showed an elevation of serum HDL-cholesterol levels. The cholesterol concentrations in the liver were raised while the cholesterol and triglyceride contents of the aorta were significantly lowered by the selected trisubstituted pyrrole.

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“…The 2,3,4-trisubstituted pyrroles (9 a-9 d) were prepared using methods previously reported [1][2][3][4][5] by heating an α-aminoketone (7 or 8) and a β-chloroenal hydride, which produces a β-ketoester (2 a-2 d) in good yield.The ketoester is treated with DMF-acetal quantitatively yielding a vinylogous amide (3 a-3 d), which is then refluxed in POCl 3 , and CH 2 Cl 2 for 2-3 h followed by hydrolysis in THF/H 2 O affording the β-chloroenal (4 a-4 d) yields of 14-34 % (Figure 1). The pTSA salt of Arch.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Cytotoxicity of Substituted Ethyl 2‐Phenacyl‐3‐phenylpyrrole‐4‐carboxylates

Evans

Smith

Holub

et al. 2003

Archiv der Pharmazie

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The substituted ethyl-2-phenacyl-3-phenylpyrrole-4-carboxylates were synthesized by a condensation of a beta-chloroenal and an alpha-aminoketone under neutral conditions. They proved to be potent cytotoxic agents against the growth of murine L1210 and P388 leukemias and human HL-60 promyelocytic leukemia, HuT-78 lymphoma, and HeLa-S(3) uterine carcinoma. Selective compounds were active against the growth of Tmolt(3) and Tmolt(4) leukemias and THP-1 acute monocytic leukemia, liver Hepe-2, ovary 1-A9, ileum HCT-8 adenocarcinoma, and osteosarcoma HSO. A mode of action study in HL-60 cells demonstrated that DNA and protein syntheses were inhibited after 60 min at 100 microM. DNA and RNA polymerases, PRPP-amido transferase, dihydrofolate reductase, thymidylate synthase, and TMP kinase activities were interfered with by the agent with reduction of d[NTP] pools. Nonspecific interaction with the bases of DNA and cross-linking of the DNA may play a role in the mode of action of these carboxylates.

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The application of disubstituted vinylogous iminium salts and related synthons to the regiocontrolled preparation of unsymmetrical 2,3,4-trisubstituted pyrroles

Cited by 51 publications

References 11 publications

Synthesis and Cytotoxicity of 2,4-Disubstituted and 2,3,4-Trisubstituted Brominated Pyrroles in Murine and Human Cultured Tumor Cells

Synthesis and Cytotoxicity of 2,4-Disubstituted and 2,3,4-Trisubstituted Brominated Pyrroles in Murine and Human Cultured Tumor Cells

Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

Synthesis and Cytotoxicity of Substituted Ethyl 2‐Phenacyl‐3‐phenylpyrrole‐4‐carboxylates

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