Hoffmann-La Roche Inc.

Enrico G Baggiolini

Milan R Uskokovic

Hsi L Lee

Gary A Truitt

Peter Michael Wovkulich

Giacomo Pizzolato

Andrew D Batcho

Bernard Michael Hennessy

Pasquale N Confalone

Alfred Boris

John Joseph Partridge, Jr

John Joseph Partridge

Shian-Jan Shiuey

Jerome Anthony Iacobelli

Thomas A Narwid

Milan R Uskovic

Milan Radoje Uskokovic'

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.

Deuterated analogs of 1,25-dihydroxycholecalciferol

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

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 is directed to a process and intermediates for the preparation of 1.alpha., 23,25-trihydroxycholecalciferol-26-oic acid 23,26-lactone.

Process for the preparation of

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 invention is directed to a process and intermediates for the preparation of 1.alpha.,25-dihydroxyergocalciferol as well as substantially pure and crystalline 1.alpha.,25-dihydroxyergocolciferol. The end-product 1.alpha.,25-dihydroxyergocalciferol is useful in the treatment of disease states which are characterized by insufficient amounts of 1.alpha., 25-dihydroxycholecalciferol.

Synthesis of 1.alpha.,25-dihydroxyergocalciferol

The invention is directed to a process and intermediates for the preparation of 1.alpha.,23(S),25-trihydroxycholecalciferol and 1.alpha.,23(R),25-trihydroxycholecalciferol. The end-products, 1.alpha.,23(S),25-trihydroxycholecalciferol and 1.alpha.,23(R),25-trihydroxycholecalciferol, are useful for the treatment of disease states which are characterized by insufficient amounts of 1,25 dihydroxycholecalciferol.

Process for the synthesis of 1.alpha.,23(S),25-trihydroxycholecalciferol

The invention is directed to a process and intermediates for the preparation of 1.alpha.,25-dihydroxyergocalciferol as well as substantially pure and crystalline 1.alpha.,25-dihydroxyergocolciferol. The end-product 1.alpha.,25-dihydroxyergocalciferol is useful in the treatment of disease states which are characterized by insufficient amounts of 1.alpha.,25-dihydroxycholecalciferol.

A process is disclosed for producing d-biotin from L or DL-cystine ester via novel intermediates.

Growing community of inventors

North Caldwell, NJ, United States of America

Enrico G Baggiolini