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At least 55 records · Page 3Linked to original sources
PubMed2001

New statins and new doses of older statins.

The need for greater reductions in LDL cholesterol, although remaining to be proven as clinically beneficial, continues to drive the development of either higher doses of currently approved and marketed statins or the development of new, more effective agents.

Atorvastatin↗
PubMed1989

Synthesis of the novel pi-(benzyloxymethyl)-protected histidine analogue of statine. Inhibition of penicillopepsin by pepstatin-derived peptides containing different statine side-chain derivatives.

The synthesis of aspartic proteinase inhibitors derived from a new histidine side-chain analogue of statine (Sta), (3S,4S)-4-amino-3-hydroxy-5-(imidazol-4-yl)pentanoic acid (HiSta, 20), is reported. Boc-HiSta(BOM)-OMe (7) was prepared in 16% overall yield from Boc-His(pi-BOM)-OH via formation of the tetramic acid derivative 11 and stereoselective cis reduction with NaBH4 to the 4-hydroxy lactam 12. Removal of the Boc group from ester 7 (enantiomeric purity ee = 88-90%) and coupling to the tripeptide segment Iva-Val-Val-OH (13) by the DCC/HOBt preactivation method followed by hydrogenolytic removal of the pi-BOM group over Pd(OH)2 on carbon gave Iva-Val-Val-HiSta-OMe (16). This new peptide 16 is a very potent inhibitor of the fungal aspartic proteinase penicillopepsin (Ki = 4.5 x 10(-9) M) that is 10 times more active than the comparable Sta-containing inhibitor 3 and 2-3 times more potent than the new (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) analogue 17 (Ki = 1.5 x 10(-8) M). However, compound 16, which has an imidazole residue at the P1 position, is a significantly weaker inhibitor of the enzyme than the corresponding analogues with the lysine (5) and ornithine (6) side chains at P1. Considerations that led to the synthesis of 16 and the results of the enzyme kinetics are discussed in detail.

Amino Acids↗
PubMed2001

Rationale and design for the SARIS trial; effect of statin on atherosclerosis and vascular remodeling assessed with intravascular sonography. Effect of Statin on Atherosclerosis and vascular Remodeling assessed with Intravascular Sonography.

PURPOSE: The SARIS study (effect of Statin on Atherosclerosis and vascular Remodeling assessed with Intravascular Sonography) is a prospective randomized multicenter trial designed to assess both morphological and functional cardiovascular effects of atorvastatin. METHODS: Participating centers will include 50 patients with normal to mildly elevated cholesterol levels eligible for balloon angioplasty and/or stent placement of the common iliac artery. Patients will be randomized to 1-year treatment with either low-dose (10 mg) or high-dose (80 mg) atorvastatin. The morphological effects of atorvastatin will be studied using intravascular ultrasound (IVUS); the effect of atorvastatin on both plaque volume and vascular remodeling seen at 1-year follow-up will be investigated. The functional cardiovascular effects of atorvastatin will be studied using dobutamine stress echocardiography (DSE); the effect of atorvastatin on myocardial coronary flow reserve at 6-months and 1-year follow-up will be investigated. The aims of the present study are noteworthy in respect that (1) IVUS is the only available technique to sensitively measure the effect of atorvastatin on both intimal hyperplasia and vascular remodeling, and (2) DSE is a non-invasive test to objectively quantify the effect of atorvastatin on the functionality of the coronary artery.

Anticholesteremic Agents↗
PubMed2005

Not all statins are alike: induced rhabdomyolysis on changing from one statin to another one.

A 59-year-old woman underwent orthotopic heart transplantation 4 years earlier. At the time of transplantation, she was receiving pravastatin at a dose of 20 mg per day; she tolerated subsequent combination with immunosuppression (cyclosporine A, prednisone, mycophenolate mofetil) very well throughout the 4 years. After switching from pravastatin to simvastatin, she developed severe muscular weakness and laboratory evidence of muscle break down. Biochemical markers of rhabdomyolysis did not subside until after repeat hemodialysis and normalized after 2 months in conjunction with improved renal function. Clinical improvement was not apparent until after 5 months.

Female↗