Asterand UK Limited

Pharmagene Laboratories Limited

Asterand UK Acquisition Limited

Robert Alexander Coleman

Alexander W Oxford

George Hynd

Kenneth Lyle Clark

Neil Victor Harris

Jonathan Mark Sutton

David Edward Clark

Garry Fenton

Richard Jon Davis

Keith Alfred James Stuttle

Edward Andrew Boyd

Mark Richard Ashton

Shirley Ann Brunton

Keith A J Stuttle

Christopher G Newton

Nicholas Tilford

Richard Anthony Borman

Janet Ann Archer

Amanda Aley

Gordon S Baxter

The present invention provides for the treatment of primary headache disorders, particularly migraine, using antagonists of the EPreceptor for prostaglandin E2. Particular EPreceptor antagonists include azole compounds of formula (I):   

Method of identifying an inhibitor of the prostanoid EP4 receptor

A compound of formula (III): or a salt, solvate and chemically protected form thereof, wherein: Ris an optionally substituted Caryl or Calkyl group; L' is a single bond, &#x2014;O&#x2014; or &#x2014;C(&#x2550;O)&#x2014;; A is selected from the group consisting of: formula (i) (ii) (iii) wherein X and Y are selected from the group consisting of: O and CR; S and CR; NH and CR; NH and N; O and N; S and N; N and S; and N and O, and where the dotted lines indicate a double bond in the appropriate location, and where Q is either N or CH; D is selected from: formula (i) (ii) (iii) (iv) (v) (vii) (viii) (ix) B is selected from the group consisting of: formula (A) (B) where Ris selected from fluoro and chloro; and Ris either: (i) &#x2014;COH; (ii) &#x2014;CONH; (iii) &#x2014;CH&#x2014;OH; or (iv) tetrazol-5-yl. 

[object Object]

Compounds of formula (I): wherein: Ris H or an optionally substituted Calkyl group; Y is either &#x2014;(CH)&#x2014;X&#x2014;, where n is 1 or 2 and X is O, S, S(&#x2550;O), S(&#x2550;O), or NR, where Ris selected from H or optionally substituted Calkyl, or Y is &#x2014;C(&#x2550;O)NR&#x2014;, where Ris selected from H, and optionally substituted Calkyl or Caryl; Ris an optionally substituted Caryl group linked to a further optionally substituted Caryl group, wherein if both Caryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings; A is a single bond or a Calkylene group; and Ris either: or wherein R is optionally substituted Calkyl, Caryl or NRR, where Rand Rare independently selected from optionally substituted alkyl;

The disclosure provides EPreceptor agonist compounds and methods for using the compounds for treating conditions which can be alleviated by agonism of an EPreceptor.

A compound of formula (I): or a salt, or chemically protected form thereof, wherein: Ris an optionally substituted phenyl;   Where Ris selected from H and Calkyl; where one of Rand Ris &#x2014;C-alkylene-Rand the other of Rand Ris H, m and n can be 0 or 1, and m+n=1 or 2; and additionally, when Ris &#x2014;C-alkylene-R, m can also be 2 or 3, and m+n=1, 2, 3 or 4, and when Ris tetrazol-5-yl, m+n may be 0; or where one of Rand Ris &#x2014;O&#x2014;CH&#x2014;R, and the other of Rand Ris H, n is 0; Ris H or optionally substituted Calkyl; Ris either: (i) &#x2014;COH; (ii) &#x2014;CONH; (iii) &#x2014;CH&#x2014;OH; or (iv) tetrazol-5-yl.

EP2 receptor agonists

Compounds of formula (I): wherein: Ris H or an optionally substituted Calkyl group; Y is either &#x2014;(CH)&#x2014;X&#x2014;, where n is 1 or 2 and X is O, S, S(&#x2550;O), S(&#x2550;O), or NR, where Ris selected from H or optionally substituted Calkyl, or Y is &#x2014;C(&#x2550;O)NR&#x2014;, where Ris selected from H, and optionally substituted Calkyl or Caryl; Ris an optionally substituted Caryl group linked to a further optionally substituted Caryl group, wherein if both Caryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings; A is a single bond or a Calkylene group; and Ris either:  wherein R is optionally substituted Calkyl, Caryl or NRR, where Rand Rare independently selected from optionally substituted Calkyl;

The present invention relates to compounds of formula I: wherein one of Rand Ris selected from the group consisting of H, and optionally substituted Calkyl, Ccycloalkyl, Ccycloalkyl-Calkyl, and phenyl-Calkyl; and the other of Rand Ris an optionally substituted Caryl group; Rand Rare either:(i) independently selected from H, R, R', SOR, C(&#x2550;O)R, (CH)NRR, where n is from 1 to 4 and Rand Rare independently selected from H and R, where R is optionally substituted Calkyl, and R&#x2032; is optionally substituted phenyl-Calkyl, or(ii) together with the nitrogen atom to which they are attached, form an optionally substituted Cheterocyclic group; and their use as pharmaceuticals, in particular for treating conditions alleviated by the antagonism of a 5-HTreceptor.

A compound of formula (I): or a salt, solvate and chemically protected form thereof, wherein one of Rand Ris:  wherein R is optionally substituted Calkyl, Caryl, or NRR, where Rand Rare independently selected from optionally substituted Calkyl; or

A compound of formula (I): or a salt, solvate and chemically protected form thereof, wherein: wherein X and Y are selected from the group consisting of:  

Compounds of formula (I): wherein: Ris H or an optionally substituted Calkyl group; Y is either &#x2014;(CH)&#x2014;X&#x2014;, where n is 1 or 2 and X is O, S, S(&#x2550;O), S(&#x2550;O), or NR, where Ris selected from H or optionally substituted Calkyl, or Y is &#x2014;C(&#x2550;O)NR&#x2014;, where Ris selected from H, and optionally substituted Calkyl or Caryl; Ris an optionally substituted Caryl group linked to a further optionally substituted Caryl group, wherein if both Caryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings; A is a single bond or a Calkylene group; and Ris either: or &#x2003;wherein R is optionally substituted Calkyl, Caryl or NRR, where Rand Rare independently selected from optionally substituted Calkyl;

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Royston, United Kingdom

Robert Alexander Coleman