Merck + Co., Inc.

Gary H Rasmusson

Richard L Tolman

Raman Kumar Bakshi

Gool F Patel

Glenn F Reynolds

Nathan G Steinberg

William K Hagmann

Philippe L Durette

Soumya P Sahoo

Derek J Von Langen

Bruce E Witzel

Thomas N Salzmann

Donald W Graham

Thomas J Lanza, Jr

David B Johnston

Shu S Yang

Georgianna S Harris

Alan D Adams

Ihor E Kopka

Ronald B Jobson

Jeffrey P Bergman

Donald F Reinhold

Craig K Esser

Josephine R Carlin

Torleif Utne

Glen E Arth, Deceased

W J VandenHeuvel

16-substituted-4-aza-androstane 5-&agr;-reductase isozyme 1 inhibitors

4-Oxa and 4-thia steroids

Compounds of the Formula I ##STR1## are inhibitors of the 5.alpha.-reductase 1 isozyme, and are useful alone, or in combination with a 5.alpha.-reductase 2 inhibitor, for the treatment of androgenic sensitive disorders such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness, and benign prostatic hyperplasia.

16-pyrazinyl-substituted-4-aza-androstane 5-.alpha.-reductase isozyme 1

The novel compounds of the present invention are those of structural formula I: ##STR1## wherein X is selected from O and S, or a pharmaceutically acceptable salt, ester, or stereoisomer thereof, and are inhibitors of 5.alpha.-reductase. The compounds of formula I are useful in the oral, systemic, parenteral or topical treatment of hyperandrogenic conditions such as acne vulgaris, seborrhea, androgenic alopecia which includes female and male pattern baldness, female hirsutism, benign prostatic hyperplasia, and the prevention and treatment of prostatic carcinoma, as well as in the treatment of prostatitis. Methods of using the compounds of formula I for the treatment of hyperandrogenic conditions such as acne vulgaris, seborrhea, androgenic alopecia, male pattern baldness, female hirsutism, benign prostatic hyperplasia, and the prevention and treatment of prostatic carcinoma, as well as the treatment of prostatitis are provided, as well as pharmaceutical compositions for the compounds of formula I. The use of compounds of formula I in combination with other active agents, for example with finasteride, or a potassium channel opener, such as minoxidil, or a retinoic acid or a derivative thereof is also taught, wherein such combinations would be useful in one or more of the above-mentioned methods of treatment or pharmaceutical compositions.

4-oxa and 4-thia steriods

16-substituted-4-aza-3-oxo-androstane as 5-alpha-reductase isozyme 1

16-substituted-4-aza-androstane 5-alpha-reductase isozyme 1 inhibitors

7.beta.-substituted-4-aza-5.alpha.-androstan-3-ones as

17 .beta.-carboxanilides of 4-aza-5.alpha.-androstan-3-ones as

Described are new 16-substituted and 7,16-disubstituted 4-aza-5.alpha.-androstan-3-ones and related compounds as 5.alpha.-reductase inhibitors.

Substituted 4-aza-5.alpha.-androstan-ones as 5.alpha.-reductase

Ester derivatives of 4-aza-steroids

Process for producing 7 .beta.-substituted-4-aza-5

17.beta.-N-monosubstituted-carbamoyl-4-5.alpha.-androst-1-en-3-ones of the formula ##STR1## wherein R.sup.1 is selected from hydrogen, methyl and ethyl and R.sup.2 is a branched chain alkyl of from 3-12 carbons, and R', R', R'' are hydrogen or methyl are active as testosterone 5.alpha.-reductase inhibitors and thus are useful topically for treatment of androgenic alopecia.

Methods of treating androgenic alopecia with finasteride

17-Ethers and thioethers of 4-aza-steroids

Described are new 7.beta.-substituted 4-aza-5.alpha.-cholestan-3-ones and related compounds as 5.alpha.-reductase inhibitors.

7.beta.-substituted-4-aza-5.alpha.-cholestan-3-ones as 5.alpha.

Growing community of inventors

Watchung, NJ, United States of America

Gary H Rasmusson