Asterand UK Limited

Pharmagene Laboratories Limited

Richard Jon Davis

Alexander W Oxford

George Hynd

Jonathan Mark Sutton

David Edward Clark

Kenneth Lyle Clark

Garry Fenton

Robert Alexander Coleman

Neil Victor Harris

Keith Alfred James Stuttle

Edward Andrew Boyd

Mark Richard Ashton

Shirley Ann Brunton

Keith A J Stuttle

Christopher G Newton

Keith J Page

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;

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;

The invention is based on the finding that the secretin receptor is expressed in tissues present in the distal lung of humans. In patient with CF, levels of the receptor are elevated compared to normal tissue. Treatment of tissue by secretin stimulates the movement of negative ions in the tissue. The invention provides methods of treatment of cystic fibrosis or COPD in a patient by administering to said patient an effective amount of an agent which triggers anion efflux in respiratory tissue via the activation of a secretin receptor.

Growing community of inventors

Royston, United Kingdom

Richard Jon Davis