Novel matrix metallo-proteinase (MMP-2) phosphonoboronate inhibitors

Pergament, Inna; Reich, Reuven; Srebnik, Morris

doi:10.1016/s0960-894x(02)00110-5

Cited by 17 publications

(13 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Last but not least, we tested the scope and limitations of our Ramberg–Bäcklund route to all‐ E ‐configured 1,ω‐dimetalopolyenes also with the goal of making the Coleman 1‐(pinacolboryl)‐6‐(tributylstannyl)hexatriene all‐ E ‐ 7 18 and the hitherto unknown 1‐bromo‐6‐(tributylstannyl)hexatriene all‐ E ‐ 76 (Schemes and , respectively). By relying on the stannylated allyl thioacetate 54 mentioned above and on an improved access via silylether 66 52 (and its desilylation with Bu 4 N + F − rather than with citric acid as previously described)52 to the known53 borylated allyl bromide 69 ,54 we obtained the B/Sn‐containing diallyl sulfide 70 (Scheme ). Oxidation to the corresponding diallylsulfone 71 succeeded with Montmorillonite‐supported oxone as an oxidant 55.…”

Section: Discussionmentioning

confidence: 99%

Stereocomplementary Syntheses of 1,ω‐DistannylatedE,Z‐Isomeric Conjugated Trienes, Tetraenes, and Pentaenes

Burghart¹,

Sorg

Brückner

2011

Chemistry A European J

View full text Add to dashboard Cite

Stereoselective syntheses of 1,6-bis(tributylstannyl)hexa-1,3,5-trienes, 1,8-bis(tributylstannyl)octa-1,3,5,7-tetraenes, and 1,10-bis(tributylstannyl)deca-1,3,5,7,9-pentaenes with various methylation patterns were achieved based on stereocomplementary C=C bond-forming reactions. All-E isomers resulted from Ramberg-Bäcklund rearrangements of distannylated diallyl-, allylpentadienyl-, or bis- (pentadienyl)sulfones. Mono-Z-configured 1,ω-bis(tributylstannyl)-1,3,5-polyenes emerged from (Sylvestre-)Julia olefinations of Bu(3)Sn-substituted enals or dienals with Bu(3)Sn-substituted allyl or pentadienyl benzothiazolylsulfones. Related Ramberg-Bäcklund approaches provided all-E-1-bromo-6-(tributylstannyl)hexa-1,3,5-triene but not all-E-1-(tetramethyldioxaborolanyl)-6-(tributylstannyl)hexa-1,3,5-triene.

show abstract

Section: Discussionmentioning

confidence: 99%

Stereocomplementary Syntheses of 1,ω‐DistannylatedE,Z‐Isomeric Conjugated Trienes, Tetraenes, and Pentaenes

Burghart¹,

Sorg

Brückner

2011

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Both boronate and phosphonate groups were incorporated into the same molecule to test the possible synergistic inhibition of MMP-2, and most of these compounds showed moderate activity (IC 50 ~50 µM) (e.g. 54) [203]. Peptidyl biphenylalkylphosphinate MMPIs were designed and evaluated as inhibitors of MMP-2 and MMP-8 [204], and these inhibitors exhibited moderate inhibitory activities with IC 50 values in the micromolar range (e.g.…”

Section: Synthetic Mmp Inhibitorsmentioning

confidence: 99%

Matrix Metalloproteinase Inhibitors as Prospective Agents for the Prevention and Treatment of Cardiovascular and Neoplastic Diseases

Sang¹,

Jin²,

Newcomer³

et al. 2006

CTMC

View full text Add to dashboard Cite

Acting on a broad spectrum of extracellular, intracellular, and membrane-associated substrates, the matrix metalloproteinases (MMPs) are critical to the biological processes of organisms; when aberrantly expressed, many pathological conditions may be born or exacerbated. The prospect of MMP inhibition for therapeutic benefit in cancer, cardiovascular disease, and stroke is reviewed here. MMP inhibitor (MMPI) development constitutes an important branch of research in both academic and industrial settings and advances our knowledge on the structure-function relationship of MMPs. Targeting MMPs in disease treatment is complicated by the fact that MMPs are indispensable for normal development and physiology and by their multi-functionality, possible functional redundancy or contradiction, and context-dependent expression and activity. This complexity was revealed by previous efforts to inhibit MMP activity in the treatment of cancer patients that yielded unsatisfactory results. This review focuses on MMPI development since the late 90s, in terms of natural products and their derivatives, and synthetic compounds of low molecular mass incorporating specific zinc-binding groups (ZBGs). A few polyphenols and flavonoids that exhibit MMPI activities may have chemopreventive and neuro- and cardiovascular-protective effects. A new generation of potent and selective MMPIs with novel ZBGs and inhibition mechanisms have been designed, synthesized, and tested. Although only one collagenase inhibitor (Periostat, doxycycline hyclate) has been approved by the Food and Drug Administration as a drug for the treatment of periodontal disease, new hope is emerging in the form of natural and synthetic MMPIs for the prevention and treatment of stroke, cardiovascular disease, cancer, and other medical conditions.

show abstract

“…The degradative activity of MMPs is tightly controlled both by the latency of the secreted enzymes as well as by the presence of naturally occurring inhibitors including general plasma proteinase inhibitors and tissue inhibitors of metalloproteinases. Imbalance between the levels of activated enzymes and their inhibitors causes a breakdown of the extracellullar matrix [47,48]. It has been shown that MMPs play a role in primary tumor growth [49].…”

Section: Biological Evaluation As Mmp-2 Inhibitorsmentioning

confidence: 99%