Patents by Inventor Milan R. Uskokovic

Milan R. Uskokovic has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 5200549
    Abstract: The invention relates to compounds of the formula ##STR1## wherein R.sub.1 is hydrogen or methyl; ##STR2## wherein R.sub.2 is lower alkyl; R.sub.3 is phenyl, or phenyl substituted by 1 to 3 substituents selected from the group consisting of halo, lower alkyl, and lower alkoxy; and R.sub.4 is hydrogen or methyl or the corresponding hydroxy acid of formula ##STR3## and R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as described above; or a pharmaceutically acceptable salt of said acid, a C.sub.1-4 alkyl ester of said acid, an acetylamino-substituted-C.sub.1-4 alkyl ester of said acid, a phenyl-dimethylamino ester of said acid or a .alpha.-monoglyceride of said acid.The compounds of formulas I and II are useful as agents for the treatment of hyperproliferative skin diseases such as psoriasis.
    Type: Grant
    Filed: September 24, 1991
    Date of Patent: April 6, 1993
    Assignee: Hoffman-La Roche Inc.
    Inventors: Peter M. Wovkulich, Milan R. Uskokovic, Ann Goldstein, John A. McLane
  • Patent number: 5149846
    Abstract: The invention is directed to deuterated vitamin D analogs, and processes and intermediates for their preparation. The end products, that is the deuterated vitamin D analogs, are useful for the treatment osteoporosis and cutaneous inflammations such as psoriasis, and contact dermatitis.
    Type: Grant
    Filed: November 16, 1989
    Date of Patent: September 22, 1992
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Enrico G. Baggiolini, Bernard M. Hennessy, Milan R. Uskokovic
  • Patent number: 5145846
    Abstract: Compounds of the formula ##STR1## wherein R is hydrogen or hydroxy, R.sub.5 is hydrogen, and A is ##STR2## with the proviso that when A is --C.tbd.C--, R.sub.5 may also be deuterium, are described.The compounds of formula I are useful as agents for the treatment of hyperproliferative disorders of the skin such as psoriasis, as agents for the treatment of neoplastic diseases such as leukemia, and as agents for the treatment of sebaceous gland diseases such as acne or seborrheic dermatitis.
    Type: Grant
    Filed: April 10, 1991
    Date of Patent: September 8, 1992
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Enrico G. Baggiolini, deceased, Bernard M. Hennessy, Shian-Jan Shiuey, Gary A. Truitt, Milan R. Uskokovic
  • Patent number: 5120722
    Abstract: The compounds 1.alpha.,25(S), 26-trihydroxy-.DELTA..sup.22 -cholecalciferol; 1.alpha.,25(R), 26-trihydroxy-.DELTA..sup.22 -cholecalciferol; 1.alpha.,25(S),26-trihydroxyergocalciferol, 1.alpha.,25(R),26-trihydroxyergocalciferol and pharmaceutical compositions comprising the compounds as well as methods of making and using these compounds are disclosed.
    Type: Grant
    Filed: March 19, 1990
    Date of Patent: June 9, 1992
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Enrico G. Baggiolini, Andrew D. Batcho, Gary A. Truitt, Milan R. Uskokovic, Peter M. Wovkulich
  • Patent number: 5110958
    Abstract: The claimed invention relates to intermediate compounds of the formula ##STR1## wherein R is hydrogen or methyl, R.sub.1 and R.sub.2 each, independently, is hydrogen, lower alkyl or aryl, or taken together are lower alkylene of from 3 to 6 carbon atoms, and the dotted (. . . ) line is an optional bond.
    Type: Grant
    Filed: May 6, 1991
    Date of Patent: May 5, 1992
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Enrico G. Baggiolini, Andrew D. Batcho, Gary A. Truitt, Milan R. Uskokovic, Peter M. Wovkulich
  • Patent number: 5087619
    Abstract: Compounds of the formula ##STR1## wherein R is hydrogen or hydroxy, R.sub.5 is hydrogen, and A is --C.tbd.C--, ##STR2## or --CH.sub.2 --CH.sub.2 --, with the proviso that when A is --C.tbd.C--, R.sub.5 may also be deuterium, are described.The compounds of formula I are useful as agents for the treatment of hyperproliferative disorders of the skin such as psoriasis, as agents for the treatment of neoplastic diseases such as leukemia, and as agents for the treatment of sebaceous gland diseases such as acne or seborrheic dermatitis.
    Type: Grant
    Filed: March 23, 1990
    Date of Patent: February 11, 1992
    Assignee: Hoffman-La Roche Inc.
    Inventors: Enrico G. Baggiolini, deceased, Barbara J. Baggiolini, Bernard M. Hennessy, Shian-Jan Shiuey, Gary A. Truitt, Milan R. Uskokovic
  • Patent number: 5075327
    Abstract: A compound and process of making thereof of formula ##STR1## wherein R.sub.1 is hydrogen; and A is alkyl; cycloalkyl; alkenyl; alkyl substituted with trifluoromethyl; phenyl; halophenyl; phenyl-C.sub.1-3 alkyl; phenyl-C.sub.1-3 alkyl substituted on the phenyl with 1 to 3 substituents selected from the group consisting of halo, C.sub.1-3 alkyl, and C.sub.1-3 alkoxy; orA is ##STR2## wherein Z is lower alkyl; R.sub.2 is hydrogen or ##STR3## R.sub.3 is hydrogen or methyl, and n is 1 to 5; Y is phenyl, is phenyl substituted by 1 to 3 substituents selected from the group consisting of halo, lower alkyl, and lower alkoxy; Y' is hydrogen or methyl; and b and d are carbon-carbon bonds or c is a carbon-carbon bond;or the corresponding hydroxy acid of formula ##STR4## wherein A, and R.sub.1, R.sub.2, R.sub.3, Y and Y' are as described above, or a pharmaceutically acceptable salt of said acid, an alkyl ester of said acid, an acetylamino-substituted-C.sub.
    Type: Grant
    Filed: November 14, 1988
    Date of Patent: December 24, 1991
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Peng C. Tang, Milan R. Uskokovic
  • Patent number: 5073568
    Abstract: The invention relates to compounds of the formula ##STR1## wherein R.sub.1 is hydrogen or methyl; A is ##STR2## or A is ##STR3## wherein R.sub.2 is lower alkyl; R.sub.3 is phenyl, or phenyl substituted by 1 to 3 substituents selected from the group consisting of halo, lower alkyl, and lower alkoxy; and R.sub.4 is hydrogen or methyl or the corresponding hydroxy acid of formula ##STR4## wherein A is ##STR5## or A is ##STR6## and R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as described above; or a pharmaceutically acceptable salt of said acid, a C.sub.1-4 alkyl ester of said acid, an acetylamino-substituted-C.sub.1-4 alkyl ester of said acid, a phenyl-dimethylamino ester of said acid or a .alpha.-monoglyceride of said acid.The compounds of formulas I and II are useful as agents for the treatment of hyperproliferative skin diseases such as psoriasis.
    Type: Grant
    Filed: November 14, 1988
    Date of Patent: December 17, 1991
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Peter M. Wovkulich, Milan R. Uskokovic, Ann Goldstein, John A. McLane
  • Patent number: 5039671
    Abstract: 26, 26, 26-Trifluoro-1.alpha., 25-dihydroxy-cholecalciferol, and the 25R or 25S epimer thereof, are described, as well as processes and intermediates utilized to prepare the same, as well as pharmaceutical compositions containing the same. 26,26,26-trifluoro 1.alpha., 25-dihydroxycholecalciferol and the 25R or 25S epimer thereof are useful agents in the treatment of disease states such as osteoporosis, oseodystrophy and leukemia.
    Type: Grant
    Filed: November 16, 1989
    Date of Patent: August 13, 1991
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Enrico G. Baggiolini, Giacomo Pizzolato, Gary A. Truitt, Milan R. Uskokovic
  • Patent number: 5021451
    Abstract: A method of treating hyperproliferative skin diseases, such as psoriasis, using a compound of formula ##STR1## wherein R.sub.1 is hydrogen when R.sub.2 is hydroxy, and R.sub.1 is methyl when R.sub.2 is hydrogen; and A is alkyl; cycloalkyl; alkenyl; alkyl substituted with trifluoromethyl; phenyl; halophenyl; phenyl-C.sub.1-3 alkyl; phenyl-C.sub.1-3 alkyl substituted on the phenyl with 1 to 3 substituents selected from the group consisting of halo, C.sub.1-3 alkyl, and C.sub.1-3 alkoxy; orA is ##STR2## wherein R.sub.3 is hydrogen or ##STR3## R.sub.4 is hydrogen or methyl, and n is 1 to 5, or the corresponding hydroxy acid of formula ##STR4## or a pharmaceutically acceptable salt of said acid, an alkyl ester of said acid, an acetylamino-substituted-C.sub.1-4 alkyl ester of said acid, a phenyl-dimethylamino ester of said acid or a .alpha.-monoglyceride of said acid.
    Type: Grant
    Filed: November 14, 1988
    Date of Patent: June 4, 1991
    Assignee: Hoffman-La Roche Inc.
    Inventors: John A. McLane, Milan R. Uskokovic
  • Patent number: 4929609
    Abstract: Compounds of the formula ##STR1## wherein R" is hydrogen or hydroxy, epimers at the 24-position of compounds of formula I, diastereomeric mixtures of compounds of formula I which are epimeric at the 24-position, and mixtures thereof, which are useful as agents for the treatment of psoriasis, and osteoporosis, are described.
    Type: Grant
    Filed: November 14, 1988
    Date of Patent: May 29, 1990
    Assignees: Hoffmann-La Roche Inc., The United States of America as represented by the Department of Agriculture
    Inventors: Andrew D. Batcho, Ronald L. Horst, Milan R. Uskokovic, Joseph L. Napoli
  • Patent number: 4898855
    Abstract: The invention is directed to deuterated vitamin D analogs, and processes and intermediates for their preparation. The end products, that is the deuterated vitamin D analogs, are useful for the treatment osteoporosis and cutaneous inflammations such as psoriasis, and contact dermatitis.
    Type: Grant
    Filed: September 14, 1987
    Date of Patent: February 6, 1990
    Assignee: Hoffman-La Roche Inc.
    Inventors: Enrico G. Baggiolini, Bernard M. Hennessy, Milan R. Uskokovic
  • Patent number: 4883791
    Abstract: The invention is directed to a method in the treatment of hypercalcitriolemic disease states which comprises administering an effective amount of 25S,26-dihydroxycholecalciferol to a host in need of such treatment.
    Type: Grant
    Filed: September 21, 1987
    Date of Patent: November 28, 1989
    Assignees: Board of Regents, The University of Texas System, Hoffman-LaRoche, Inc.
    Inventors: Charles Y. C. Pak, Milan R. Uskokovic, Joseph E. Zerwekh
  • Patent number: 4804502
    Abstract: Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen or hydroxy and R.sub.2 is hydrogen or fluorine are described. The compounds of formula I are useful as agents in the treatment of disease states characterized by metabolic calcium deficiencies. Examplary of such disease states are osteoporosis and renal osteodystrophy.
    Type: Grant
    Filed: January 20, 1988
    Date of Patent: February 14, 1989
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Enrico G. Baggiolini, John J. Partridge, Shian-Jan Shiuey, Gary A. Truitt, Milan R. Uskokovic
  • Patent number: 4652405
    Abstract: 1.alpha.,25-Dihydroxy-24R-fluorocholecalciferol and 1.alpha.,25-dihydroxy-24S-fluorocholecalciferol, analogs of 1.alpha.,25-dihydroxy-cholecalciferol which is physiologically the most active metabolite of vitamin D.sub.3, are synthesized in a multistep process from the known substance 1.alpha.,3.beta.-dihydroxyandrost-5-en-17-one. The new analogs are characterized by the ability to increase intestinal calcium transport, increase serum calcium and phosphate concentrations and to increase the deposition of these minerals in bones. These compounds will find a ready application as substitutes for natural 1.alpha.,25-dihydroxycholecalciferol in the treatment of disease states characterized by metabolic calcium and phosphate deficiencies.
    Type: Grant
    Filed: August 6, 1982
    Date of Patent: March 24, 1987
    Assignee: Hoffman-La Roche Inc.
    Inventors: John J. Partridge, Shian-Jan Shiuey, Milan R. Uskokovic
  • Patent number: 4634692
    Abstract: 1.alpha.,25-Dihydroxy-24R-fluorocholecalciferol and 1.alpha.,25-dihydroxy-24S-fluorocholecalciferol, analogs of 1.alpha.,25-dihydroxy-cholecalciferol which is physiologically the most active metabolite of vitamin D.sub.3, are synthesized in a multistep process from the known substance 1.alpha.,3.beta.-dihydroxyandrost-5-en-17-one. The new analogs are characterized by the ability to increase intestinal calcium transport, increase serum calcium and phosphate concentrations and to increase the deposition of these minerals in bones. These compounds will find a ready application as substitutes for natural 1.alpha.,25-dihydroxycholecalciferol in the treatment of disease states characterized by metabolic calcium and phosphate deficiencies.
    Type: Grant
    Filed: April 11, 1984
    Date of Patent: January 6, 1987
    Assignee: Hoffmann-La Roche Inc.
    Inventors: John J. Partridge, Shian-Jan Shiuey, Milan R. Uskokovic
  • Patent number: 4632784
    Abstract: The invention is directed to a process and intermediates for the preparation of 1.alpha., 23,25-trihydroxycholecalciferol-26-oic acid 23,26-lactone.
    Type: Grant
    Filed: July 30, 1984
    Date of Patent: December 30, 1986
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Enrico G. Baggiolini, Milan R. Uskokovic, Peter M. Wovkulich
  • Patent number: 4617297
    Abstract: The present invention relates to the method of treating disease states characterized by higher than normal levels of endogenously produced 1.alpha.,25 dihydroxy-cholecalciferol or conditions where there is an increased sensitivity to 1.alpha., 25 dihydroxy-cholecalciferol by administering to an organism suffering from such a disease state a pharmaceutically effective amount of the R or S epimer of 1.alpha.,25,26 trihydroxy-cholecalciferol.
    Type: Grant
    Filed: April 3, 1984
    Date of Patent: October 14, 1986
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Alfred Boris, John J. Partridge, Milan R. Uskokovic
  • Patent number: 4612308
    Abstract: The syntheses of 25,26-dehydro-1.alpha.,23S-dihydroxycholecalciferol, 25,26-dehydro-1.alpha.,23R-dihydroxycholecalciferol, and the epimeric mixture thereof which are useful as differentiation inducing agents and anti-proliferation agents are described, 25,26-dehydro-1.alpha.,23S-dihydroxycholecalciferol 25,26-dehydro-1.alpha.,23R-dihydroxycholecalciferol and the epimeric mixture thereof are useful for treating tumors and leukemia, and osteoporosis.
    Type: Grant
    Filed: November 29, 1984
    Date of Patent: September 16, 1986
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Enrico G. Baggiolini, Gary A. Truitt, Milan R. Uskokovic, Peter M. Wovkulich
  • Patent number: 4599330
    Abstract: The present invention relates to a method of preventing milk fever which comprises administering to a preparturient female ruminant an effective amount of 24,24-difluoro-1.alpha.,25-dihydroxycholecalciferol.
    Type: Grant
    Filed: May 17, 1982
    Date of Patent: July 8, 1986
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Alfred Boris, John J. Partridge, Milan R. Uskokovic