Synthesis and SAR of α-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors

Zhang, Yuemei; Fan, Xiaodong; Xiang, Bangping; Chakravarty, Devraj; Scannevin, Robert H.; Burke, Sharon L.; Karnachi, Prabha; Rhodes, Kenneth J.; Jackson, Paul F.

doi:10.1016/j.bmcl.2006.03.065

Cited by 14 publications

(5 citation statements)

References 17 publications

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“…Zhang et al disclosed a novel family of carboxylic acidbased -sulfone inhibitors 22 (Table 4) with excellent enzyme potency and good selectivity over MMP-1 [100]. The SAR of both P 1 and P1/P2 has shown that a straight, hydrophobic P 1 group with the optimal length was preferred and an amido-or imido-type group was critical for MMP-9 inhibitory activity.…”

Section: Carboxylic Acid-based Mmpismentioning

confidence: 97%

Selective Matrix Metalloproteinase Inhibitors for Cancer

Li¹,

Shi²,

Tang³

et al. 2009

CMC

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The matrix metalloproteinases are a family of nearly 30 enzymes that are intimately involved in tissue remodeling. Disease processes associated with the matrix metalloproteinases are generally related to imbalance between the inhibition and activation of matrix metalloproteinases resulting in excessive degradation of the extracellullar matrix. These include osteoarthritis, rheumatoid arthritis, tumor metastasis and congestive heart failure. Despite massive research and development efforts, there are only two drugs launched on the market: periostat (doxycycline), a tetracycline used for periodontal disease and glucosemine sulfate, for osteoarthritis. Possible reasons for the low success rate of matrix metalloproteinase inhibitors in the clinic are mainly from unwanted side effects caused by their lack of selectivity, since inhibition of collagenase-1 may be responsible for the musculoskeletal side effects observed clinically with broad-spectrum inhibitors. Considering these data, many efforts were directed to developing a more selective second generation of inhibitors against the specific matrix metalloproteinases believed to be involved in the different pathologies. This review mainly focuses on selective matrix metalloproteinase inhibitors development on matrix metalloproteinases in terms of antitumor since the late 90s, in terms of synthetic compounds of low molecular mass incorporating specific zinc-binding groups, natural products and their derivatives. Through these methods, new hope is emerging in the form of synthetic and natural matrix metalloproteinase inhibitors for the prevention and treatment of cancer.

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Section: Carboxylic Acid-based Mmpismentioning

confidence: 97%

Selective Matrix Metalloproteinase Inhibitors for Cancer

Li¹,

Shi²,

Tang³

et al. 2009

CMC

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“…Cyclic variants, including prinomastat (7), based on numerous heterocycles have also been reported. In addition, sulfone hydroxamates, such as RS 130830 (8) are also known [6][7][8] (Fig. 2).…”

Section: Introductionmentioning

confidence: 98%

Role of Sulfonamide Group in Matrix Metalloproteinase Inhibitors

Cheng¹,

Wang²,

Fang

et al. 2008

CMC

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Matrix metalloproteinases (MMPs) play an important role in many physiological and pathological processes. MMP inhibitors have been considered as potential therapeutics for neoplasitc, rheumatic and cardiovascular diseases. Our group and others have been developing pyrrolidine scaffold-based MMP inhibitors for a number of years, and numerous compounds have been reported in the literature. These compounds can be classified as sulfonamide pyrrolidine derivatives, proline-containing peptidomimetics and acyl pyrrolidine derivatives. These synthetic MMP inhibitors show low nanomolar activity for some MMP subclasses, thus confirming pyrrolidine ring an excellent scaffold from which to design MMP inhibitors. This review will focus primarily on the structure, activity and selectivity profiles of pyrrolidine scaffold-based MMP inhibitors.

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“…Brominated enamine 5m was reduced with NaBH 4 and treated with sodium azide to produce α-azido-β-amino acid ester 11 in 74% overall yield. Although several methods are known to prepare these types of compounds, − these syntheses provide alternative methods, which compared favorably to most of the current procedures in terms of yield and operational convenience.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective Chlorination and Bromination of Enamides and Enamines via an Electrostatic Attraction Effect Using (1,1-Diacetoxyiodo)benzene and a Halide Source

Xing

2015

J. Org. Chem.

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The direct chlorination and bromination of (E)-enamines and (Z)-enamides to the corresponding (Z)-configurated α-chloroenamines, α-bromoenamines, and α-chloroenamides have been realized using NiCl2·6H2O or tetrabutyl ammonium bromide as a halide source and (1,1-diacetoxyiodo)benzene as an oxidant. The high stereoselective reactions which produce products with only (Z)-configurations can be attributed to the structure of the intermediates, the conformations of which are controlled by the electrostatic attractions between the positively charged nitrogen atoms and the oxygen atoms of the carbonyl group. This type of electrostatic effect has never been reported in olefin halogenations. For this reason, the three-membered bromonium ion is only a minor intermediate in the enamine bromination pathway. These methods open pathways to prepare α-chloroenamines and α-chloroenamides, which are not accessible via the currently used methods.

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Synthesis and SAR of α-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors

Cited by 14 publications

References 17 publications

Selective Matrix Metalloproteinase Inhibitors for Cancer

Selective Matrix Metalloproteinase Inhibitors for Cancer

Role of Sulfonamide Group in Matrix Metalloproteinase Inhibitors

Stereoselective Chlorination and Bromination of Enamides and Enamines via an Electrostatic Attraction Effect Using (1,1-Diacetoxyiodo)benzene and a Halide Source

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