Ferring B.v.

Vantia Limited

Gary Robert William Pitt

David Michael Evans

Peter Hudson

Doreen Mary Ashworth

Richard Jeremy Franklin

Christopher Martyn Yea

Andrzej Roman Batt

David Philip Rooker

Michael Bryan Roe

The invention concerns compounds according to general formulae 1, wherein Gis an amine. Compounds according to the invention are vasopressin Vreceptor agonists. Pharmaceutical compositions of the compounds are useful as antidiuretic agents. 

Heterocyclic condensed compounds useful as antidiuretic agents

This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, Vand Vare both H, OMe or F, or one of Vand Vis Br, Cl, F, OH, OMe, OBn, OPh, O-acyl, N, NH, NHBn or NH-acyl and the other is H, or Vand Vtogether are &#x2550;O, &#x2014;O(CH)O&#x2014; or &#x2014;S(CH)S&#x2014;; Wis either O or S; Xand Xare both H, or together are &#x2550;O or &#x2550;S; Y is ORor NRR; R, R, Rand Rare independently selected from H, lower alkyl, lower alkyloxy, F, Cl and Br; Ris selected from H and lower alkyl; Rand Rare independently selected from H and lower alkyl, or together are &#x2014;(CH)&#x2014;; n=3, 4, 5, 6; and p is 2 or 3. The compounds are agonists at the vasopressin V2 receptor and are useful as antidiuretics and procoagulants. The invention further comprises pharmaceutical compositions incorporating these vasopressin agonists, which compositions are particularly useful in the treatment of central diabetes insipidus, nocturnal enuresis and nocturia.

Condensed azepines as vasopressin agonists

Compounds according to general formula 1, wherein A-Aare selected from Aand Awhere Ais either &#x2550;CR&#x2014; or &#x2550;N&#x2014; and Ais &#x2014;NR&#x2014;, &#x2014;O&#x2014; or &#x2014;S&#x2014;; Ais either a covalent bond or A, provided that when Ais a covalent bond one of A-Amust be Aand the other two must be Aand when Ais Athen all of A-Amust be A; Ris selected from H, NHY' and COY, in which case Ris H, or Rand R2 may both be methyl or together represent &#x2550;O; R, Rand Rare each independently selected from H and lower alkyl groups; R, R, R, R, R, Rand Rare each independently selected from H, lower alkyl groups, NH, halogens (F, Cl and Br) O-alkyl, CHNMand CF; Ris selected from H, F, Cl Br, NO, NH, OH, Me, Et, OMe, NMeand CF; Ris selected from H, methyl and ethyl; W is selected from &#x2550;CH&#x2014; and &#x2550;N&#x2014;; X is selected from CH, O, S, SO, NH and N lower alkyl; Yis selected from CO-lower alkyl, CO(CH)Y, CO(CH)COYand CO(CH)NHCOY, where b is 1-3; Y2 is selected from OR, NRRand NH(CH)COY, where c is 1-3; Yis selected from ORand NRR; Ris selected from H, lower alkyl and (CH)R, where a is 0-4; Rand Rare each independently selected from H, lower alkyl and (CH)Ror together are &#x2014;(CH)-Z-(CH&#x2014;; Ris OH a phenyl group or an aromatic heterocycle selected from pyridyl, pyrimidinyl, pyrazinyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl and thiadiazolyl, each of which may optionally have a lower alkyl group substituent; and Z is selected from O, CH, S, SO, NH and N-lower alkyl, are new. They are useful in the treatment of breast and prostate cancer, endometriosis and benign prostate hyperplasia, in the regulation of fertility, and in in vitro fertilisation.

Non-peptide GnRH antagonists

Compounds according to general formula (1), wherein Ris H or CN, Xis S, O, SOor CH, Xis O, S or CH, Xis NRor a carbonyl or thiocarbonyl group and Ris RRN, R(CH)OC(&#x2550;O), R(CH)OC(&#x2550;S), RRNC(&#x2550;O), RRNC(&#x2550;S); R(CH)C(&#x2550;O), R(CH)C(&#x2550;S) or R(CH)SO, m is 1&#x2013;3 and n is 0&#x2013;4 are new. The compounds of the invention are inhibitors of dipeptidyl peptidase IV. Pharmaceutical compositions of the compounds of the invention, or pharmaceutically acceptable salts thereof, are useful in the treatment of, inter alia, type 2 diabetes 

Inhibitors of dipeptidyl peptidase IV

Compounds according to formula (1), wherein Ris H or CN, Xis S, O, SOor CH, Xis CO, CHor a covalent bond, Het is a nitrogen-containing heterocycle and n is 1&#x2013;5 are new. The compounds of the invention are inhibitors of dipeptidyl peptidase IV. Pharmaceutical compositions of the compounds of the invention, or pharmaceutically acceptable salts thereof, are useful in the treatment of, inter alia, type 2 diabetes 

This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, Vand Vare both H, OMe or F, or one of Vand Vis Br, Cl, F, OH, OMe, OBn, OPh, O-acyl, N, NH, NHBn or NH-acyl and the other is H, or Vand Vtogether are &#x2550;O, &#x2014;O(CH)O&#x2014; or &#x2014;S(CH)S&#x2014;; Wis either O or S; Xand Xare both H, or together are &#x2550;O or &#x2550;S; Y is ORor NRR; R, R, Rand Rare independently selected from H, lower alkyl, lower alkyloxy, F, Cl and Br; Ris selected from H and lower alkyl; Rand Rare independently selected from H and lower alkyl, or together are &#x2014;(CH)&#x2014;; n=3, 4, 5, 6; and p is 2 or 3. The compounds are agonists at the vasopressin V2 receptor and are useful as antidiuretics and procoagulants. The invention further comprises pharmaceutical compositions incorporating these vasopressin agonists, which compositions are particularly useful in the treatment of central diabetes insipidus, nocturnal enuresis and nocturia. 

Compounds according to general formula (1), and pharmaceutically acceptable salts thereof, wherein V is a covalent bond or NH, X is selected from CH , O and N-alkyl, Z is either S or &mdash;CH&boxH;CH&mdash;, R and R are independently selected from H, F, Cl, Br and alkyl, R is selected from OH, O-alkyl and NR R , R and R are each independently H or alkyl, or together are &mdash;(CH ) &mdash;, p is 0, 1, 2, 3 or 4, and q is 4 or 5, are new. They are agonists at the asopressin V receptor and are useful as antidiuretics and pro-coagulants.

Growing community of inventors

Hampshire, United Kingdom

Gary Robert William Pitt