Asterand UK Limited

Aventis Pharmaceuticals Inc.

Sanofi-aventis

Pharmagene Laboratories Limited

Centelion Sas

Kenneth Lyle Clark

Alexander W Oxford

George Hynd

Robert Alexander Coleman

Neil Victor Harris

Jonathan Mark Sutton

David Edward Clark

Garry Fenton

Richard Jon Davis

Keith Alfred James Stuttle

Kun Guo

Marco Pagnoni

Edward Andrew Boyd

Mark Richard Ashton

Shirley Ann Brunton

Yuri D Ivashchenko

Christopher G Newton

Keith A J Stuttle

George H Searfoss, Iii

Yuri Ivashchenko

Richard Anthony Borman

Janet Ann Archer

Amanda Aley

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. 

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The present invention relates to human Akt3 proteins and polypeptides. The invention also relates to isolated nucleic acids encoding human Akt3, to vectors containing them and to their therapeutic uses, in particular for gene therapy. Expression of Akt3 inhibits cell death associated with hypoxia, apoptosis or necrosis.

AKT nucleic acids, polypeptides, and uses thereof

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

Human Akt3 nucleic acid and uses thereof

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

The present invention relates to variants of TRAF2 which demonstrate the ability to inhibit the TNF &#x3b1; signaling pathway. In particular, applicants have isolated a splice variant of TRAF2 referred to hereinafter as 'TRAF2 truncated' or 'TRAF2TR' and a TRAF2 expression construct with enhanced dominant negative properties, hereafter referred to as &#x201c;TRAF2 truncated-deleted&#x201d; or &#x201c;TRAF2TD&#x201d;. Both TRAF2TR and TRAF2TD have the ability to inhibit the TNF &#x3b1; signaling pathway and in TRAF2TD, this ability is greatly enhanced, greatly reducing the response to TNF &#x3b1; binding.

Variants of TRAF2 which act as an inhibitor of TNF-alpha (TNF&#x3b1;) signaling pathway

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 present invention relates to variants of TRAF2 which demonstrate the ability to inhibit the TNF &#x3b1; signaling path-way. In particular, applicants have isolated a splice variant of TRAF2 referred to hereinafter as 'TRAF2 truncated' or 'TRAF2TR' and a TRAF2 expression construct with enhanced dominant negative properties, hereafter referred to as &#x201c;TRAF2 truncated-deleted&#x201d; or &#x201c;TRAF2TD&#x201d;. Both TRAF2TR and TRAF2TD have the ability to inhibit the TNF &#x3b1; signaling pathway and in TRAF2TD, this ability is greatly enhanced, greatly reducing the response to TNF &#x3b1; binding.

Growing community of inventors

Linton, United Kingdom

Kenneth Lyle Clark