β-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors: Part 1. Design, synthesis, and lead identification

Yang, Shyh‐Ming; Scannevin, Robert H.; Wang, Bingbing; Burke, Sharon L.; Wilson, Lawrence J.; Karnachi, Prabha; Rhodes, Kenneth J.; Lagu, Bharat; Murray, William V.

doi:10.1016/j.bmcl.2007.11.119

Cited by 30 publications

(15 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An overview of SAR of β-N-biaryl ether sulfonamide hydroxamates studied for the inhibition of MMP-2 and MMP-9 by Yang et al 191 is presented in Figure 34. This figure shows the flexibility of the S1′ pocket, which can be pushed down to accommodate the bulky hydrophobic group of the inhibitors.…”

Section: Mmp Inhibitionmentioning

confidence: 99%

QSAR Studies on Hydroxamic Acids: A Fascinating Family of Chemicals with a Wide Spectrum of Activities

Gupta

2015

Chem. Rev.

View full text Add to dashboard Cite

Section: Mmp Inhibitionmentioning

confidence: 99%

QSAR Studies on Hydroxamic Acids: A Fascinating Family of Chemicals with a Wide Spectrum of Activities

Gupta

2015

Chem. Rev.

View full text Add to dashboard Cite

“…As it was mentioned before, this chemical class is large and has provided potent MMPIs. Recently, a series of -N-biaryl ether sulfonamide hydroxamates has been reported as novel potent gelatinase inhibitors (Tables 15-18) [124,125]. Structure-activity relationship studies suggested that the methanesulfonyl group together with -N-biaryl ether type P1' moiety is the optimal combination to obtain low nanomolar activities against gelatinases.…”

Section: N-sulfonyl-2-aminoacetic Hydroxamates and N-sulfonyl-3-aminomentioning

confidence: 99%

“…The reported synthesis of N-Sulfonyl-3-aminopropanoic hydroxamates starts with the formation of sulfonamides from biaryl anilines and sulfonyl chlorides (Scheme 8) [124]. These sulfonamides are reacted with methyl (S)-glycidate to form the corresponding -hydroxyesters with the desired stereochemistry, which were converted into hydroxamates using standard conditions.…”

Section: N-sulfonyl-2-aminoacetic Hydroxamates and N-sulfonyl-3-aminomentioning

confidence: 99%

“…These sulfonamides are reacted with methyl (S)-glycidate to form the corresponding -hydroxyesters with the desired stereochemistry, which were converted into hydroxamates using standard conditions. The -hydroxyl group was modified by methylation or, after activation with triflic anhydride, by SN 2 displacement reaction with both ammonia and several cyclic or acyclic amines to give a series of -amino hydroxamates [124]. …”

Section: N-sulfonyl-2-aminoacetic Hydroxamates and N-sulfonyl-3-aminomentioning

confidence: 99%

“…Inhibitory Activity Against MMP-2 of N-Sulfonyl-2-aminoacetic Hydroxamates and N-Sulfonyl-3-aminopropanoic Hydroxamates[124] …”

mentioning

confidence: 99%

See 2 more Smart Citations

MMP-2 Selectivity in Hydroxamate-Type Inhibitors

Serra

Bruczko²,

Zapico³

et al. 2012

CMC

View full text Add to dashboard Cite

Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases involved in physiological and pathological processes, through the cleavage of extracellular matrix. MMPs are capable of degrading essentially all matrix components, which is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. The vertebrates MMP family includes at least 26 enzymes (23 have been known in humans) with only MMP-1, 2, and 7 experimentally validated as targets for antitumoral drug design. However, inhibition of MMP-1 has been hypothesized to be the cause of the clinically observed musculoskeletal syndrome when broad spectrum inhibitors are used. On the other hand, MMP-9 is a tricky enzyme, since its inhibition might be useful in treating patients with early-stage cancers, but MMP-9 is an anti-target in patients with advanced disease. So, MMP-9 inhibition should also be prevented. Therefore, selective MMP-2 inhibition arises as a pursued profile for MMP binders. Among them, hydroxamates have been extensively studied as small molecule drug candidates characterized by an effective zinc-binding group plus additional side chains responsible for the selectivity. This article pays particular attention to MMP-2 selectivity on hydroxamate-type inhibitors, especially against MMP-9, and their chemical structure, SAR, general synthetic methods, and molecular modelling studies are here reviewed in order to inspire further design of new effective anticancer agents.

show abstract