Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-03-15
1997-07-15
Bond, Robert T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
540456, A61K 31395, C07D49804
Patent
active
056483619
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US98/06679, filed 16, Jul. 1993, which claims priority of U.S. application 07/915,145, filed 17 Jul. 1992.
BACKGROUND OF THE INVENTION
This invention relates to rapamycin derivatives, pharmaceutical compositions comprising such derivatives, and methods of treatment of pathogenic fungi, methods of inducing immunosuppression and methods of treating carcinogenic tumors utilizing such rapamycin derivatives.
Rapamycin is a naturally occurring macrocyclic triene antibiotic which can be produced by culturing an organism in an aqueous nutrient medium. Its structure may be illustrated as follows: ##STR1##
At least one rapamycin-producing strain of Streptomyces hygroscopius was deposited with the Northern Utilization and Research Division, Agricultural Research Service, U.S. Department of Agriculture, Peoria, Ill., U.S.A. under accession number NRRL 5491. Rapamycin, and methods for its preparation by culturing NRRL 5491 are disclosed by U.S. Pat. No. 3,929,992, issued Dec. 30, 1975, the entire disclosure of which is hereby incorporated by reference.
SUMMARY OF THE INVENTION
This invention relates to novel rapamycin derivatives of the formula: ##STR2## wherein:
R.sup.1 is selected from the group consisting of .dbd.O (--OR.sub.6,H) and (H,H);
R.sup.2 is selected from the group consisting of .dbd.O (H,H), and (H, OH);
R.sup.3 and R.sup.6 are independently selected from the group consisting of --H, --C(.dbd.O)R.sup.7, --C(.dbd.O)OR.sup.7, --C(.dbd.O)NHR.sup.7, and --C(.dbd.S)OR.sup.7 ;
R.sup.4 is selected from the group consisting of .dbd.O and (H, OR.sup.6); or R.sup.3 and R.sup.4 can be taken together to form a bridge of the formula A-C(R.sup.8)(R.sup.9)-O-B, where A is a bond to the oxygen bonded to the carbon at the 28-position and B is a bond to the carbon at the 30-position;
R.sup.5 is selected from the group consisting of --H and C.sub.1 -C.sub.4 alkyl;
R.sup.7 is selected from the group consisting of C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.6 cycloalkyl, aryl groups, and heterocyclic groups;
R.sup.8 and R.sup.9 are independently selected from the group consisting of H, C.sub.1 to C.sub.6 alkyl, or R.sup.8 and R.sup.9 taken together are .dbd.O;
provided that, when R.sup.4 is .dbd.O then R.sup.2 is (H, OH);
and all pharmaceutically acceptable salts, hydrates or solvates thereof.
This invention also relates to a pharmaceutical composition comprising an effective amount of one or more compounds of Formula II and a pharmaceutically acceptable carrier or diluent.
This invention also relates to a method of inhibiting the growth of pathogenic fungi in a human or other animal in need thereof which comprises administering an effective, non-toxic amount of one or more compounds of Formula II to such human or other animal.
This invention also relates to a method of inducing immunosuppression in a human or other animal in need thereof which comprises administering an effective, non-toxic amount of one or more compounds of Formula II to such human or other animal.
In addition, this invention relates to a method of treating carcinogenic tumors in a human or other animal comprising administering an effective, non-toxic amount of one or more compounds of Formula II to such human or other animal.
Still further, this invention relates to a method of preparing novel compounds of Formula II wherein R.sup.4 is (H,OH) and R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 are as described above, comprising contacting a compound of the formula ##STR3## with a mixture of cerium trichloride and sodium cyanoborohydride.
DETAILED DESCRIPTION OF THE INVENTION
When any substituent or variable (e.g., aryl, alkoxyl, R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.6, etc.) occurs more than one time in the formula of any of the compounds of Formula II, such variable or substituent definition on each occurrence is independent of its definition at every other occurrence, unless otherwise indicated. Combinations of substituents and/or variables are in a constituent of the compounds of the i
REFERENCES:
patent: 4316885 (1982-02-01), Rakhit
patent: 4650803 (1987-03-01), Stella et al.
patent: 5023262 (1991-06-01), Caufield et al.
patent: 5023263 (1991-06-01), Von Burg
patent: 5023264 (1991-06-01), Caufield et al.
patent: 5102876 (1992-04-01), Caufield et al.
patent: 5118677 (1992-06-01), Caufield et al.
patent: 5138051 (1992-08-01), Hughes et al.
Holt Dennis Alan
Luengo Juan Ignacio
Rozamus, Jr. Leonard Walter
Bond Robert T.
Lentz Edward T.
SmithKline Beecham Corporation
Stercho Yuriy P.
Venetianer Stephen A.
LandOfFree
Rapamycin derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Rapamycin derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Rapamycin derivatives will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1492517