Akzo Nobel N.v.

N.v. Organon

Pharmacopeia Drug Discovery, Inc.

Jaap Van Der Louw

Dirk Leysen

Hubert Jan Jozef Loozen

Pedro Harold Han Hermkens

Neeltje Miranda Teerhuis

Herman Thijs Stock

Johannes Petrus Maria Lommerse

Marinus Bernard Groen

Marcel Evert De Gooijer

Johannes Antonius Joseph Leemhuis

John J Baldwin

Roland Ellwood Dolle

Koc-Kan Ho

Shawn David Erickson

Michael H J Ohlmeyer

Steven G Kultgen

James Inglese

Adolph C Bohnstedt

Johannes Antonius Hamersma

Paolo Giovanni Martino Conti

Anja Wiersma

Marcel Evert De Gooyer

Christian Heijmans

Arij Jan Grootenhuis

Roberta Buma Bursi

Roberta Burma Bursi

Marcel E De Gooijer

This invention provides non-steroidal compounds with affinity for the androgen receptor and utility for androgen-receptor related treatments, having a structure according to the formula or a salt or hydrate form thereof.

Non-steroidal androgens compounds

The compounds of the subject invention have a structure according to formula I: wherein each of the substituents is given the definition as set forth in the specification and claims, or a salt or hydrate form thereof.

Androgens

Indoles useful in the treatment of androgen-receptor related diseases

The invention provides 19-nor-D-homosteroids, having a mixed androgenic/progestagenic profile, which are orally active, prevent trabecular bone mineral density (BMD) loss, and which lack liver toxicity, having a structure according to the formula (I) wherein, Ris O, or NOR, with R being hydrogen, (C1-6)alkyl, or (C1-6)acyl, Ris methyl or ethyl, and Ris hydrogen or (C)acyl. 

Steroids having a mixed androgenic and progestagenic profile

Compounds containing the pyrimidine nucleus and their use to treat diseases and conditions related to inappropriate Interleukin-8 receptor activity are disclosed. The compounds are of the formula IIn these compounds, Q is preferably unsubstituted and substituted heterocyclyl; U is usually hydrogen or fluorine; and V is preferably hydrogen, halogen, alkyl, &#x2014;O&#x2014;alkyl or &#x2014;S-alkyl. A representative example is:

Pyrimidine derivatives as IL-8 receptor antagonists

Disclosed are androgenic steroids of the (14&#x3b2;,17&#x3b1;)-17-(hydroxymethyl) type. The invention relates to an improvement thereof, which is based on the presence of a &#x3b2;-oriented, annellated cyclopropyl group which includes carbon atoms 16 and 17 of the steroid skeleton, i.e. a 16,17&#x3b2;-methylene moiety. These steroids show an unexpectedly high androgenic potency.

14 &#x3b2;, 16, 17-methylene steroids as novel androgens

Androgenic steroids having a (14&#x3b2;,17&#x3b1;-)-17-(hydroxymetheyl) configuration, useful for the preparation of male contraceptives and pharmaceutical formulations for the treatment of androgen insufficiency.

14-&#x3b2;, 17-&#x3b1;-hydroxymethylandrostane derivatives as androgens

Orally active androgens

Orally Active androgens are derivative of 7&agr;-methyl-19-nortestosterone. The compounds satisfy formula (I) wherein R is O, (H,H), (H,OR), NOR, with R being hydrogen, (C )alkyl, or (C )acyl; R is selected from the group consisting of (C )alkyl, isopropyl, (C )1-alkenyl, isopropenyl, 1,2-proandienyl, or (C )1-alynyl, each optionally substituted by halogen; or R is cyclopropyl, or cyclopropenyl, each optionally substituted by (C )alkyl, or halogen; R is hydrogen, (C )alkyl, or ethenyl; R is (C )alkyl; R is hydrogen, or (C )acyl; and the dotted lines indicate optional bonds.

The disclosed invention relates to the unexpected finding of novel steroids which are characterized by a 14&bgr;,15&bgr;-cyclopropane ring and a 17&agr; hydroxymethyl group. These steroids according to the invention are found to have in common an androgenic activity. They can be used for the preparation of an agent for male contraception, as well as for the preparation of a medicament for the treatment of androgen insufficiency.

14&bgr;,15&bgr;-methylene-17&agr;-hydroxymethyl-androgens

(Androst-5-en-17beta -yl)alkyl sulfoxides and sulfones and their use for control of fertility

Novel, orally active androgens are 7&agr;-substituted &Dgr;,-nandrolone derivatives. The compounds satisfy the general formula:

The invention relates to 17&bgr;-allyloxy(thio)alkyl-androstane derivatives having general formula (I) wherein R,is (H, OR), (H, OSO,H) or NOR; with R being H, (C,)alkyl or (C,)acyl; each of R,and R,is independently hydrogen or (C,)alkyl; n is 0, 1 or 2; X is O, S, S(O) or S(O),; each of R,and R,is independently hydrogen or (C,)alkyl; each of R,, R,and R,is independently hydrogen, phenyl, halogen or (C,)alkyl, optionally substituted by hydroxy, (C,) alkoxy or halogen; or R,and R,together with the carbon atom to which they are bound form a (C,)cycloalkane ring; or R,and R,together with the carbon atoms to which they are bound form a (C,) cycloalkene ring; and wherein the dotted lines indicate a &Dgr;,or a &Dgr;,double bond, or a pair of conjugated double bonds selected from &Dgr;,, &Dgr;,and &Dgr;,; or a pharmaceutically acceptable salt thereof. The compounds of the invention have meiosis activating activity and can be used for the control of fertility.

17&bgr;-allyloxy(thio)alkyl-androstane derivatives for the modulation of meiosis

The invention relates to 17&bgr;-aryl(arylmethyl)oxy(thio)alkyl-androstane derivatives having general formula (I), wherein R,is (H,OR), (H,OSO,H) or NOR; with R being H, (C,)alkyl or (C,)acyl; each of R,and R,is independently hydrogen or (C,)alyl; n is 0, 1, or 2; X is O, S, S(O) or S(O),; m is 0 or 1; each of R,, R,and R,is independently hydrogen, hydroxy, (C,)alkoxy, halogen, NR,R,or (C,)alkyl, optionally substituted by hydroxy, alkoxy, halogen or oxo; each of R,and R,is independently hydrogen or (C,)alkyl, and wherein the dotted lines indicate a &Dgr;,or a &Dgr;,double bond, or a pair of conjugated double bonds selected from &Dgr;,, &Dgr;,and &Dgr;,; or a pharmaceutically acceptable salt thereof. The compounds of the invention have meiosis regulating activity and can be used for the control of fertility.

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Oss, Netherlands

Jaap Van Der Louw