Design and Therapeutic Application of Matrix Metalloproteinase Inhibitors. (Chem. Rev. 1999, 99, 2735−2776. Published on the Web September 8, 1999).

Whittaker, Mark; Floyd, Christopher D.; Brown, Peter de Nully; Gearing, A. J. H.

doi:10.1021/cr0100345

Cited by 39 publications

(34 citation statements)

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“…The crude material was purified by column chromatography (1:9:90 30% aqueous NH 4 OH/MeOH/CH 2 Cl 2 ) to yield 4b as a yellow oil (17.8 mg, 0.084 mmol, 12%). 1 …”

Section: -(Hexylamino)-4-(hydroxyamino)-3-cyclobutene-12-dione (4b)mentioning

confidence: 99%

“…Purification was performed by column chromatography (1:9:90 30% aqueous NH 4 OH/MeOH/CH 2 Cl 2 ) to yield a yellowish flaky solid (0.238 g, 0.88 mmol, 70%). 1 Hydroxy(1-methylethyl)amino]-4-(L-isoleucine methyl ester)-3-cyclobutene-1,2-dione (6b) Compound 6b (0.034 g, 0.11 mmol, 26%) was prepared as a colorless solid starting from 3e (0.080 g, 0.432 mmol) and 5a (0.120 g, 0.56 mmol) according to the procedure used for the preparation of 4b. 1 (Hydroxymethylamino)-4-(D,L-norleucine methyl ester)-3-cyclobutene-1,2-dione (6c) Compound 6c (0.09 g, 0.33 mmol, 45%) was prepared from 3b (0.118 g, 0.75 mmol), D,Lnorleucine methyl ester HCl salt (0.136 g, 0.75 mmol) and KOH (0.042 g, 0.75 mmol) according to the procedure used for preparing 6a.…”

Section: -(Hydroxymethylamino)-4-(l-isoleucine Methyl Ester)-3-cyclomentioning

confidence: 99%

“…1 (Hydroxymethylamino)-4-(D,L-norleucine methyl ester)-3-cyclobutene-1,2-dione (6c) Compound 6c (0.09 g, 0.33 mmol, 45%) was prepared from 3b (0.118 g, 0.75 mmol), D,Lnorleucine methyl ester HCl salt (0.136 g, 0.75 mmol) and KOH (0.042 g, 0.75 mmol) according to the procedure used for preparing 6a. 1 …”

Section: -(Hydroxymethylamino)-4-(l-isoleucine Methyl Ester)-3-cyclomentioning

confidence: 99%

“…1 171.6, 165.9, 165.3, 56.0, 52.8, 41.4, 31.8, 30.1, 15.4; HRMS-FAB (M + Na + ) calcd for C 11 H 16 N 2 O 5 SNa 311.0678, found 311.0685.…”

Section: -(Hydroxymethylamino)-4-(l-methionine Methyl Ester)-3-cyclomentioning

confidence: 99%

“…Purification was performed by column chromatography (5:95 MeOH/CH 2 Cl 2 ) yielding 10a as a colorless oil (0.637 g, 4.42 mmol, 66%). 1 …”

Section: L-tert-leucine Methyl Amide (10a)mentioning

confidence: 99%

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Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

2005

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A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono-or dipeptides that are designed to bind in the S1′ and S2′ subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me) OH provided the highest level of inhibition among the chelating groups that were tested, and LeuTle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC 50 value of 95 μM. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC 50 value of 15 μM.

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“…The crude material was purified by column chromatography (1:9:90 30% aqueous NH 4 OH/MeOH/CH 2 Cl 2 ) to yield 4b as a yellow oil (17.8 mg, 0.084 mmol, 12%). 1 …”

Section: -(Hexylamino)-4-(hydroxyamino)-3-cyclobutene-12-dione (4b)mentioning

confidence: 99%

Section: -(Hydroxymethylamino)-4-(l-isoleucine Methyl Ester)-3-cyclomentioning

confidence: 99%

Section: -(Hydroxymethylamino)-4-(l-isoleucine Methyl Ester)-3-cyclomentioning

confidence: 99%

“…1 171.6, 165.9, 165.3, 56.0, 52.8, 41.4, 31.8, 30.1, 15.4; HRMS-FAB (M + Na + ) calcd for C 11 H 16 N 2 O 5 SNa 311.0678, found 311.0685.…”

Section: -(Hydroxymethylamino)-4-(l-methionine Methyl Ester)-3-cyclomentioning

confidence: 99%

“…Purification was performed by column chromatography (5:95 MeOH/CH 2 Cl 2 ) yielding 10a as a colorless oil (0.637 g, 4.42 mmol, 66%). 1 …”

Section: L-tert-leucine Methyl Amide (10a)mentioning

confidence: 99%

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Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

2005

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Neue Entwicklungen in der asymmetrischen Mehrkomponenten‐Reaktion

2005

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Unter der asymmetrischen Mehrkomponenten‐Reaktion versteht man die Synthese von chiralen Verbindungen aus drei oder mehr gleichzeitig zusammengegebenen Reaktionspartnern. Diese Art der Zugabe und Umsetzung hat gegenüber klassischen divergenten Strategien eine Reihe von Vorteilen, darunter ein geringerer Aufwand an Kosten, Zeit und Energie sowie eine bessere Umweltverträglichkeit. Dies und die hohe Stereoselektivität mancher Reaktionen werden diese neue Synthesestrategie für die chemische Industrie und für Hochschulen zunehmend wichtig machen. In diesem Aufsatz werden die Vorzüge, aber auch die Probleme asymmetrischer Mehrkomponenten‐Reaktionen diskutiert.

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Asymmetric Multicomponent Reactions (AMCRs): The New Frontier

2005

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Asymmetric multicomponent reactions involve the preparation of chiral compounds by the reaction of three or more reagents added simultaneously. This kind of addition and reaction has some advantages over classic divergent reaction strategies, such as lower costs, time, and energy, as well as environmentally friendlier aspects. All these advantages, together with the high level of stereoselectivity attained in some of these reactions, will force chemists in industry as in academia to adopt this new strategy of synthesis, or at least to consider it as a viable option. The positive aspects as well as the drawbacks of this strategy are discussed in this Review.

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Design and Therapeutic Application of Matrix Metalloproteinase Inhibitors. (Chem. Rev. 1999, 99, 2735−2776. Published on the Web September 8, 1999).

Cited by 39 publications

References 0 publications

Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

Neue Entwicklungen in der asymmetrischen Mehrkomponenten‐Reaktion

Asymmetric Multicomponent Reactions (AMCRs): The New Frontier

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