Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Gool F Patel

Gary H Rasmusson

Richard L Tolman

Raman Kumar Bakshi

Donald W Graham

James M Balkovec

Georgianna S Harris

Susan D Aster

Amjad Ali

Bruce E Witzel

Steven L Colletti

Sherman Tim Waddell

Mitree M Ponpipom

Milana M Maletic

Xin Gu

Cameron James Smith

Nancy J Kevin

Steven H Olson

Richard Beresis

Rolf Thieringer

Anne Hermanowski-Vosatka

Steven S Mundt

2,5-Diaryl-1,2,4-triazole derivatives of structural formula I are selective inhibitors of the 11&#x3b2;-hydroxysteroid dehydrogenase Type 1 enzyme (11&#x3b2;-HSD-1). The compounds are useful for the treatment of diabetes, hyperglycemia, obesity, insulin resistance, atherosclerosis, dyslipidemia, hyperlipidemia, hypertension, and Metabolic Syndrome. Also disclosed are novel compounds of structural formula II which are inhibitors of 11&#x3b2;-HSD-1.

Diaryltriazoles as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1

The present invention encompasses compounds of Formula (I) and Formula (II) or pharmaceutically acceptable salts or hydrates thereof, which are useful as selective glucocorticoid receptor ligands for treating a variety of autoimmune and inflammatory diseases or conditions. Pharmaceutical compositions and methods of use are also included. 

Selective spirocyclic glucocorticoid receptor modulators

Compounds having Formula (I), including pharmaceutically acceptable salts and prodrugs thereof: are selective inhibitors of the 11&#x3b2;-HSD1 enzyme. They inhibit the 11&#x3b2;-HSD1-mediated conversion of cortisone and other 11-keto-glucocorticoids to cortisol and other 11&#x3b2;-hydroxy-glucocorticoids. The 11&#x3b2;-HSD1 inhibitors therefore decrease the amount of cortisol in target tissues, thereby modulating the effects of cortisol. Modulation of cortisol may be effective in controlling non-insulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Syndrome X, and other symptoms associated with NIDDM or with excess cortisol in the body 

11-&#x3b2;-hydroxysteroid dehydrogenase 1 inhibitors useful for the treatment of diabetes, obesity and dyslipidemia

4-Oxa and 4-thia steroids

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

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 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.

Described are new 17.beta.-aryl ester carboxylates of 4-aza-5.alpha.-androstan-3-ones and related compounds and the use of such compounds as 5.alpha.-reductase inhibitors for treatment of benign prostatic hyperplasia and other hyperandrogenetic related disorders.

Aryl ester derivatives of 3-oxo-4-aza-androstane 17-.beta.-carboxylates

17.beta.-acyl-3-carboxy-androsta-3,5-dienes as testosterone 5.alpha.-reductase inhibitors of the formula: ##STR1## wherein R is C.sub.3 -C.sub.8 cycloalkyl, which can be substituted with C.sub.1 -C.sub.4 alkoxy or C.sub.6 -C.sub.12 aryl, which can be substituted with one or more of: --OH, --OC.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkyl, --(CH.sub.2).sub.m OH, --(CH.sub.2).sub.n COOH, including protected --OH, where m is 1-4, n is 1-3, and pharmaceutically acceptable salts or esters thereof. Also described is a pharmaceutical formulation. The above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.

17.beta.-acyl-3-carboxy-androsta-3,5-dienes as testosterone

N-monosubstituted adamantyl/norbornanyl 17.beta.-carbamides of 3-carboxy-androst-3,5-dienes as testosterone 5.alpha.-reductase inhibitors of the formula: ##STR1## wherein R is a hydrocarbon radical selected from substituted or unsubstituted 1- or 2-adamantyl or 1-, 2- or 7-norbornanyl and pharmaceutically acceptable salts or esters thereof. Also described is a pharmaceutical formulation. The above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.

N-monosubstituted adamantyl/norbornanyl 17.beta.-carbamides of

New intermediates in the synthesis of 17.beta.-acyl-3-carboxy-androsta-3,5-dienes, of the formula: ##STR1## wherein R.sup.2 is 2-thiopyridyl, and

Intermediates in the synthesis of

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Califon, NJ, United States of America

Gool F Patel