Akzo N.v.

Akzo Nobel N.v.

Merck Sharp + Dohme B.v.

Merck Sharp + Dohme Corp.

Ralf Plate

Johannes H Wieringa

Christiaan Gerardus Johannes Maria Jans

Paolo Giovanni Martino Conti

Cornelis Marius Timmers

Adrianus Petrus Antonius De Man

Duncan R Rae

Guido Jenny Rudolf Zaman

Willem Frederik Johan Karstens

Rogier Christian Buijsman

Pedro Harold Han Hermkens

Scott James Lusher

Willem Hendrik Abraham Dokter

Wilhelmina Maria Bagchus

Christianus Johannes Van Koppen

Sjoerd F Van Aelst

Franciscus H Van Bakel

Gerhardus J Heeres

The present invention relates the use of a compound, a pharmaceutical composition, compounds and a kit for treating or preventing disorders in a mammal responsive to TSH receptor mediated pathways, including disorders such as hyperthyroidism, Graves' disease, Graves Ophthalmopathy, Graves' associated pretibial dermopathy, nodular goitre and thyroid cancer comprising administering to said mammal an effective amount of a tetrahydroquinoline compound of Formula (I) or an pharmaceutically acceptable salt thereof. 

TSH receptor antagonizing tetrahydroquinoline compounds

This invention relates to novel amino acid derivatives of formula (I) wherein the R groups have the following meanings: &#x2014;Ris &#x2014;H or &#x2014;(1-4C)alkyl; &#x2014;Ris &#x2014;C(O)Ror &#x2014;S(O)R; &#x2014;Ris &#x2014;H, &#x2014;(1-4C)alkyl or &#x2014;OR; &#x2014;Ris &#x2014;H, &#x2014;(1-4C)alkyl or &#x2014;OR; &#x2014;Ris &#x2014;H or &#x2014;C(R)NOR; &#x2014;Ris &#x2014;H, -halogen, -cyano; &#x2014;(1-6C)alkyl, &#x2014;(2-6C)alkenyl or &#x2014;(2-6C)alkynyl, all optionally substituted with -amino, -hydroxyl or -halogen; &#x2014;Ris &#x2014;H, -cyano, -halogen, -nitro; &#x2014;(1-6C)alkyl, &#x2014;(2-6C)alkenyl, &#x2014;(2-6C)alkynyl or &#x2014;O(1-6C)alkyl, all optionally substituted with -amino, -hydroxyl or -halogen; -(hetero)aryl, optionally substituted with -cyano, -halogen, &#x2014;(1-4C)alkyl, &#x2014;(1-4C)alkoxy, &#x2014;(1-4C)alkoxy(1-4C)alkyl or -(hetero)aryl; &#x2014;C(R)NOR; &#x2014;C(O)N(R); &#x2014;C(O)R18, &#x2014;C(O)OR, &#x2014;NHC(O)R, or &#x2014;NHS(O)R; &#x2014;Ris &#x2014;H, -halogen, -cyano, or &#x2014;(1-4C)alkyl, optionally substituted with -halogen; &#x2014;Ris &#x2014;H or &#x2014;(1-4C)alkyl; &#x2014;Ris &#x2014;H; &#x2014;Ris &#x2014;H, -cyano or &#x2014;(1-4C)alkyl; &#x2014;Ris &#x2014;H, &#x2014;(1-4C)alkyl, -halogen or -formyl; &#x2014;Ris &#x2014;H, -halogen, -cyano, &#x2014;(1-4C)alkyl or -(hetero)aryl; or a pharmaceutically acceptable salt thereof. The compounds of this invention are highly specific for the glucocorticoid receptor and may be used for treating inflammatory diseases. 

Non-steroidal compounds useful as glucocorticoid receptor modulators

The present invention relates to compounds having general Formula (I) or a pharmaceutically acceptable salt thereof. The present invention also relates to pharmaceutical compositions comprising said compounds and the use of these derivatives to modulate glucocorticoid receptor activity. 

Non steroidal glucocorticoid receptor modulators

The invention concerns a 3-methylene steroid derivative having general formula (1) wherein R is H or together with R forms a &bgr;-epoxide or R is absent if there is a 5-10 or 4-5 double bond; R is (C -C ) alkyl or CF ; R is &bgr;H, &bgr;CH or together with R forms a &bgr;-epoxide or R is absent if there is a 5-10 double bond; R is H, lower alkyl; Y is &lsqb;H, H&rsqb;, &lsqb;OH, H&rsqb;, &boxH;O, &lsqb;OH, lower alkyl&rsqb;, &lsqb;OH, (C2-C5)alkenyl&rsqb;, &lsqb;OH, (C -C )alkynyl&rsqb; or (C -C ) alkylidene, whereby said alkyl, alkenyl, alkynyl and alkylidene is optionally halogenated; &boxH;NOR , whereby R is H, lower alkyl; dotted lines represent an optional double bond, or prodrugs thereof for the treatment of arthritic diseases and/or autoimmune diseases.

3-methylene steroid derivatives

The invention is concerned with a tetrahydropyrimidine derivative having formula I ##STR1## wherein R.sub.1 is hydrogen;

Tetrahydropyrimidine derivatives

The invention relates to a piperazine derivative having the formula ##STR1## wherein each .phi. is a phenyl group which may independently be substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, CF.sub.3, and halogen, and Y is O or S, or a pharmaceutically acceptable salt thereof. The piperazine derivatives have sigma receptor affinity, and may be used for the treatment of psychosis.

Piperazine derivatives

The invention relates to a 3-quinuclidine derivative having the formula I ##STR1## wherein X is O or S, and R represents one to five substituents independently selected from hydrogen, hydroxy, lower alkyl, lower alkoxy, lower aralkyloxy, lower alkanoyloxy, halogen, NO.sub.2, CF.sub.3, CN, NR.sub.1 R.sub.2, and COR.sub.3, in which R.sub.1 and R.sub.2 are independently selected from hydrogen, lower alkyl, and lower alkanoyl, and R.sub.3 is selected from OH, lower alkyl, lower alkoxy, and NR.sub.4 R.sub.5, wherein R.sub.4 and R.sub.5 are independently hydrogen or lower alkyl; or pharmaceutically acceptable salts thereof.

3-quinuclidine derivatives

The invention relates to pyrazole derivative having formula I ##STR1## wherein

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Oss, Netherlands

Ralf Plate