Inducer-Specific Regulators of Tumor Necrosis Factor Alpha Production.

Miyachi, Hiroyuki; Azuma, Arata; Hioki, Erika; Kobayashi, Yoshiro; Iwasaki, Shigeo; Hashimoto, Yuichi

doi:10.1248/cpb.44.1980

Cited by 16 publications

(19 citation statements)

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“…In the case of compound 23, of which the S-and R-isomers were both inactive in enhancement of TPA-induced TNF-α production, the S-isomer was inactive and the R-isomer was a very potent inhibitor of OAinduced TNF-α production. Taken together, these results indicated that the bidirectional TNF-α production regulating activities can be separated by the use of a optically active phthalimide analogs [74][75].…”

Section: Synthetic Analogsmentioning

confidence: 66%

“…Therefore, it would be of great benefit if the bidirectional TNF-α production regulating activity could be separated, because inhibition, but not enhancement, of TNF-α production is considered to be the mechanism of the beneficial effects of thalidomide. With this goal in mind, Miyachi and coworkers described the synthesis and determination of TNF-α production regulating activity of a series of phthalimide derivatives [74][75]. These derivatives, planned by structural modification of thalidomide (1) were designed by introduction of fluorine atoms into the phthalimide moiety and a methyl group at the α-position, aiming the enhancement of activity and selectivity.…”

Section: Synthetic Analogsmentioning

confidence: 99%

“…The percentage of inhibition of LPS-induced TNF-α production in human monocytes at 50 µM are indicated in parentheses. pure and assayed as inducer-specific bidirectional regulation of TNF-α production by HL-60 cells at concentration of 0,3 µM [74][75].…”

Section: Synthetic Analogsmentioning

confidence: 99%

“…In the efforts for identification of new thalidomide analogs with anti-inflammatory properties, novel N-phenylphthalimide derivatives (74)(75)(76)(77)(78)(79)(80)(81) were described [97]. These derivatives were planned by modifications in the structures of lead-compounds LASSBio-468 (71e) and LASSBio-595 (72e).…”

Section: Lassbio-542 (2-[2-(13-dioxo-23-dihidro-1h-2-isoindolyl)phementioning

confidence: 99%

“…In the series of 2-phenoxy-phthalimide derivatives (74)(75)(76)(77), the racemate 75 (LASSBio-542) was the most active, inhibiting 50% of TNF-α production and neutrophil influx, similar to the effect of thalidomide. These results indicate that the functionalization in the ortho position of the phenyl ring of N-phenyl-phthalimide moiety led to the same inhibitory pro- Fig.…”

Section: Lassbio-542 (2-[2-(13-dioxo-23-dihidro-1h-2-isoindolyl)phementioning

confidence: 99%

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Thalidomide and Analogs as Anti-Inflammatory and Immunomodulator Drug Candidates

Lima¹,

Fraga²,

Koatz³

et al. 2006

AIAAMC

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Thalidomide ([2-(2,6-dioxo-hexahydro-3-(R,S)-pyridinyl)-1,3-isoindolinedione]), well known by its teratogenic effect, caused birth defects in up to 12,000 children in the 1960s. More recently, this drug was approved by the US Food and Drug Administration for the treatment of erythema nodosum leprosum, under restricted-use program, and a variety of new possible therapeutic applications have been described. This article will accomplish a review of medicinal chemistry aspects of thalidomide and state of the art in the development of new anti-inflammatory and immunomodulator drug candidates designed using thalidomide as lead-compound.

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Section: Synthetic Analogsmentioning

confidence: 66%

Section: Synthetic Analogsmentioning

confidence: 99%

Section: Synthetic Analogsmentioning

confidence: 99%

Section: Lassbio-542 (2-[2-(13-dioxo-23-dihidro-1h-2-isoindolyl)phementioning

confidence: 99%

Section: Lassbio-542 (2-[2-(13-dioxo-23-dihidro-1h-2-isoindolyl)phementioning

confidence: 99%

See 3 more Smart Citations

Thalidomide and Analogs as Anti-Inflammatory and Immunomodulator Drug Candidates

Lima¹,

Fraga²,

Koatz³

et al. 2006

AIAAMC

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5′-Substituted Thalidomide Analogs as Modulators of TNF-α

Teubert

Zwingenberger²,

Wnendt

et al. 1998

Arch. Pharm. Pharm. Med. Chem.

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The synthesis of 5′‐substituted thalidomide analogs is described. The amino acids 2 necessary to synthesize the target compounds were prepared by Michael reaction. Condensation of 2 with phthalic anhydrides followed by reaction with urea yielded 4 as diastereomeric mixtures. Furthermore glutethimide (5) was brominated by an improved method and the resulting compound 6 was reacted in several steps with sodium azide, hydrogen, and phthalic anhydride to give 8. In a similar manner, 6 was reacted with sodium azide and various phthalic anhydrides to give 9, 10, and 11. All final compounds were tested in vitro for their inhibitory activity on the release of TNF‐α, using stimulated peripheral mononuclear blood cells (PBMCs). Compounds with an additional aromatic substituent in position 5’ of the thalidomide molecule were more active than thalidomide. Compound 11 was able to reduce increased levels of IL‐2 in vitro.

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