Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor.

Systematic variation of the so-called P-pocket moiety of benzamidrazone-based selective thrombin inhibitors led to the discovery of LB30057. It is potent (Ki = 0.38 nM for human thrombin), selective (Ki = 3290 nM for bovine trypsin), and orally bioavailable (58% oral bioavailability in dogs). LB30057 was efficacious in thrombosis animal models.

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Cited by: 0 articles | PMID: 12723936

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Small molecules (chemicals) in ChEMBL (Showing 10 of 25)

N-ethyl-N-cyclopentyl-3-(4-hydrazonoformamidephenyl)-2-[(2-naphthylsulfonyl)amino]propanamide(CHEMBL - CHEMBL156082)
Plasminogen(CHEMBL - CHEMBL1801)
Tissue-type plasminogen activator(CHEMBL - CHEMBL1873)
Thrombin(CHEMBL - CHEMBL204)
Trypsin(CHEMBL - CHEMBL2095204)
Coagulation factor X(CHEMBL - CHEMBL244)
Benzamidrazone derivative(CHEMBL - CHEMBL347158)
N-(n-propyl)-N-cyclopentyl-3-(4-hydrazonoformamidephenyl)-2-[(2-naphthylsulfonyl)amino]propanamide(CHEMBL - CHEMBL347371)
N-methyl-N-cyclopropyl-3-(4-hydrazonoformamidephenyl)-2-[(2-naphthylsulfonyl)amino]propanamide(CHEMBL - CHEMBL348175)
N-hydroxy-N-cyclopentyl-3-(4-hydrazonoformamidephenyl)-2-[(2-naphthylsulfonyl)amino]propanamide(CHEMBL - CHEMBL350901)

Search life-sciences literature (45,105,671 articles, preprints and more)

Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor.

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References

Title not supplied

Design and synthesis of potent and highly selective thrombin inhibitors.

Title not supplied

Potent and selective thrombin inhibitors incorporating the constrained arginine mimic l-3-piperidyl(N-guanidino)alanine at P1.

Design, synthesis, and evolution of a novel, selective, and orally bioavailable class of thrombin inhibitors: P1-argininal derivatives incorporating P3-P4 lactam sulfonamide moieties.

Sanderson, P.E.; Lyle, T.A.; Dorsey, B.D.; Varsolona, R.J. PCT Patent Application WO 9740024-A, 1997.

Title not supplied

Oh, Y.S.; Kim, S.S.; Hwang, S.Y.; Yun, M.K.; Hwang, S.R.; Hong, S.W.; Lee, Y.H.; Jeong, Y.N.; Lee, K.; Shin, Y.S. European Patent Application EP 0739886, 1996.

The venous antithrombotic effect of LF 1351 in the rat following oral administration.

The effect of thrombin inhibition in a rat arterial thrombosis model.

Citations & impact

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Citations of article over time

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Smart citations by scite.ai
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1016/s0960-894x(98)00079-1

Article citations

Synthesis, and antitumor activity of some N1-(coumarin-7-yl) amidrazones and related congeners.

Progress in the design of low molecular weight thrombin inhibitors.

Thrombin inhibitors built on an azaphenylalanine scaffold.

Antithrombotic therapy in atrial fibrillation: ximelagatran, an oral direct thrombin inhibitor.

LB30057, an orally effective direct thrombin inhibitor, prevents arterial and venous thrombosis in rats and dogs.

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Data that cites the article

Small molecules (chemicals) in ChEMBL (Showing 10 of 25)

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Search life-sciences literature (45,105,671 articles, preprints and more)

Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor.

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Title not supplied

Title not supplied

Sanderson, P.E.; Lyle, T.A.; Dorsey, B.D.; Varsolona, R.J. PCT Patent Application WO 9740024-A, 1997.

Title not supplied

Oh, Y.S.; Kim, S.S.; Hwang, S.Y.; Yun, M.K.; Hwang, S.R.; Hong, S.W.; Lee, Y.H.; Jeong, Y.N.; Lee, K.; Shin, Y.S. European Patent Application EP 0739886, 1996.

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