.alpha.-phosphonosulfonate squalene synthetase inhibitors

Details .alpha.-phosphonosulfonate squalene synthetase inhibitors .alpha.-phosphonosulfonate squalene synthetase inhibitors

1994-07-05

1998-01-27

Higel, Floyd D.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

514 94, 514114, 514127, 514 79, 514 80, 514 81, 514 86, 514 89, 514 92, 544232, 544243, 544244, 546 23, 540450, 540471, 540474, 540542, 548112, 548113, 558 45, 562 17, 562 21, 562 23, 562 35, C07F 938, C07F 9553, C07F 96506, C07F 96512, A61K 3166

Patent

active

057123969

ABSTRACT:
.alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.

REFERENCES:
patent: 2336230 (1943-12-01), Dickey et al.
patent: 2965665 (1960-12-01), Gaertner et al.
patent: 3595880 (1971-07-01), Firestone
patent: 3657282 (1972-04-01), Christensen et al.
patent: 3819676 (1974-06-01), Chistensen et al.
patent: 4032521 (1977-06-01), Christensen et al.
patent: 4059431 (1977-11-01), Takematsu et al.
patent: 4254215 (1981-03-01), Kramp et al.
patent: 4696693 (1987-09-01), Swerdloff et al.
patent: 4781865 (1988-11-01), Liu
patent: 4795815 (1989-01-01), Ternansky
patent: 4937367 (1990-06-01), Castaldi et al.
patent: 5011938 (1991-04-01), Barnett et al.
patent: 5272128 (1993-12-01), Rosen et al.
patent: 5391743 (1995-02-01), Ebtino et al.
Burton, D.J., J. Am. Chem. Soc. 1989, 111, 1773-1776.
Su, D. et al, Can. J. Chem. 1989, 67, 1795-1799.
Farrington, G.K., et al, J. Med. Chem. 1985, 28, 1668-1673.
Musicki, B. et al, T.S. Tetrahedron Lett. 1991, 32, 1267-1270.
Carretero, J.C. et al, Tatrahedron 1987, 43, 5125-5134.
Callahan, L. et al, Analytical biochemistry 1989, 177, 67-71.
Amin, Dilip et al, "Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis", Journal of Lipid Research, vol. 33, 1993, pp. 1657-1663.

Affiliated with

Also associated with

Rating

.alpha.-phosphonosulfonate squalene synthetase inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with .alpha.-phosphonosulfonate squalene synthetase inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and .alpha.-phosphonosulfonate squalene synthetase inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-343600