Hoffmann-la Roche Inc.

Gary A Truitt

Milan R Uskokovic

Enrico G Baggiolini

Shian-Jan Shiuey

Peter Michael Wovkulich

Giacomo Pizzolato

John Joseph Partridge

Andrew D Batcho

Bernard Michael Hennessy

Enrico G Baggiolini, Deceased

Maurice Kent Gately

Barbara J Baggiolini

Milan R Uskovic

Bruce H Devens

William R Benjamin

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.

Vitamin D3 analogs

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.

Trihydroxy-cholecacliferol and trihydroxy-ergocalciferol for treating

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.

Compounds, process and intermediates

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.

Vitamin D.sub.3 analogs

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.

Trifluorinated-1.alpha.,25S-dihydroxy vitamin D3 compounds

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, osteodystrophy and leukemia.

Novel trifluorinated vitamin D3 intermediates

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.

Vitamin D compounds

The invention relates to pharmaceutical compositions comprising at least one Vitamin D derivative and a method of using the pharmaceutical compositions in suppressing immune responses.

Immunosuppressive agents

Novel hexafluoro-cholecalciferol compounds and processes for preparing such compounds are disclosed. Intermediates utilized in the preparation of such compounds and pharmaceutical preparations containing these compounds are also disclosed.

Fluorinated vitamin D.sub.3 compounds

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.

25,26-Dehydro-1.alpha.,23(S,R)-dihydroxycholecalciferol and its epimers

The syntheses of 25,26-dehydro-1.alpha.,24R-dihydroxycholecalciferol and 25,26-dehydro-1.alpha.,24S-dihydroxycholecalciferol and the epimeric mixture which are useful as differentiation inducing agent and anti-proliferation agents are described. 25,26-dehydro-1.alpha.,24R-dihydroxycholecalciferol, 25,26-dehydro-1.alpha.,24S-dihydroxycholecalciferol, and the epimeric mixture are useful in treating osteoporosis, tumors and leukemia.

Growing community of inventors

Bloomfield, NJ, United States of America

Gary A Truitt