N.v. Organon

Merck Sharp + Dohme B.v.

Msd Oss B.v.

Herman Thijs Stock

Neeltje Miranda Teerhuis

Jaap Van Der Louw

Pedro Harold Han Hermkens

Johannes Petrus Maria Lommerse

Gerrit Herman Veeneman

Cornelis Marius Timmers

Hubert Jan Jozef Loozen

Arthur A Oubrie

Fredericus Antonius Dijcks

Scott James Lusher

Fredricus Antonius Dijcks

The present invention relates to novel N-substituted azetidine derivatives &#x3c; of the formula (I); wherein SERMF is a Selective Estrogen Receptor Modilator fragment; X is no atom, O, S, CH2, carbonyl, N&#x2014;R5; R1 is H, (C1-8)alkyl, (C3-8)cycloalkyl, (C3-6)heterocycloalkyl, (C2-6)alkenyl, (C2-6)alkynyl, (C1-4)alkylcarbonyl, (C1-4)alkoxy(C2-4)alkyl, (C3-6)cycloalkyl(C1-3)-alkyl, (C3-6)heterocycloalkyl(C1-3)alkyl, each independently optionally substituted with one or more halogen, nitrile, hydroxyl or (C1-2)alkyl; R5 is H, (C1-3)alkyl, optionally substituted with one or more fluorine; R17, R18 and R19 are independently of each other H, fluorine, nitrile or (C1-3)-alkyl, optionally substituted with one or more fluorine; or a prodrug, isotopically-labelled derivative or pharmaceutically acceptable salt thereof, &#x3e; to pharmaceutical compositions comprising these compounds and to their use in therapy, in particular to their use for the prevention or treatment of ovulatory dysfunction, uterine cancer, endometrium cancer, ovarian cancer, endometriosis, osteoporosis, prostate cancer, benign prostatic hypertrophy, and breast cancer, in particular ER-positive breast cancer, more in particular ER-positive, hormone treatment-resistant breast cancer. Said N-substituted azetidine derivatives have estrogen receptor alpha (ERa) antagonistic and&#x2014;in certain embodiments&#x2014;selective estrogen receptor downregulating (SERD) activity in ER-positive breast cancer cells. 

N-substituted azetidine derivatives

The invention relates to ring-annulated dihydropyrrolo[2,1-a]isoquinoline compounds according to general Formula I or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.

Ring-annulated dihydropyrrolo[2,1-&#x3b1;]isoquinolines

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 present invention relates to novel tetrahydronaphthalen-2-ol derivatives, to pharmaceutical compositions comprising these compounds and to their use in therapy, in particular to their use for the manufacture of a medicament for the prevention or treatment of lower urinary tract symptoms, benign prostate hyperplasia, prostate cancer, hot flushes, anxiety, depression, breast cancer, medullary thyroid carcinoma, ovarian cancer, inflammatory bowel disease, arthritis, endometriosis, and colon cancer.

Tetrahydronaphthalen-2-ol derivatives

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

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Oss, Netherlands

Herman Thijs Stock