University College London

Virginia Commonwealth University

Ucl Business Plc

Canbex Therapeutics Limited

The Kennedy Institute of Rheumatology

Barravore Limited

David Baker

David Lawrence Selwood

Masahiro Okuyama

Cristina Visintin

Gareth Pryce

Marc Feldmann

Billy R Martin

Raj K Razdan

Anu Mahadevan

Gyorgy Szabadkai

Michael Roland Duchen

Julia Marie Hill

Justin Neil Darrel Warne

John Leslie Turk

David Selwood

The present invention relates to conjugates of cyclosporin with quinolium mitochondrial targeting groups, and their therapeutic uses.

Quinolinium conjugates of cyclosporin

The present disclosure relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Z is selected from OH, NHCHCHF, NHCH(Me)CHOH and NHCHCHOH; X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO-alkyl, alkenyl, CN, NH, hydroxy, halo, alkoxy, CFand nitro; Y is a polar functional group selected from OH, NO, CN, COR, COOR, NRR, CONRR, SOH, SO&#x2014;R, SONRRand CF, where each of Rand Ris independently H or a hydrocarbyl group; A is phenyl or pyridyl; and B is (CH)where n is 0; with the proviso that: (i) when A is phenyl, and Z is OH, X&#x2014;Y is other than C&#x2261;C&#x2014;(CH)COH, C&#x2261;C&#x2014;(CH)COMe, (CH)COH. Uses of such compounds as medicaments for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors are provided.

Modulator

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Z is ORor NRRwherein each of Rand Ris independently H, or a hydrocarbyl group; X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO-alkyl, alkenyl, CN, NH, hydroxy, halo, alkoxy, CFand nitro; Y is a polar functional group selected from OH, NO, CN, COR, COOR, NRR, CONRR, SOH, SO&#x2014;R, SONRRand CF, where each of Rand Ris independently H or a hydrocarbyl group; A is an aryl or heteroaryl group, each of which may be optionally substituted; and B is (CH2)where n is 0, 1, 2, 3, 4 or 5; with the proviso that: (i) when A is phenyl, n is 0, and Z is OH, X&#x2014;Y is other than meta-C&#x2261;&#x2014;C&#x2014;(CH)COH, meta-C&#x2261;&#x2014;C&#x2014;(CH)OH, meta-C&#x2261;C&#x2014;(CH)COMe, meta-(CH)COH, ortho-CHCOH, ortho-(CH)COH and ortho-(CH)COH; and (ii) when A is phenyl, n is 0, and Z is OMe, X&#x2014;Y is other than meta-C&#x2261;C&#x2014;(CH)OH. Further aspects of the invention relate to the use of such compounds in the preparation of a medicament for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors.

The invention compounds and methods for the treatment of motor disorders. In particular, the invention provides eicosanoid analogs which are effective in ameliorating motor disorders such as spasticity caused by multiple sclerosis (MS).

Anti-spasticity of an eicosanoid analog

An amphibious vehicle has a drive system comprising a driven wheel ( ) of the vehicle with which is associated a guide ( ) having inlet ( ) and outlet ( ) means and the wheel being formed such that when the wheel is in water its rotation draws water into the guide via said inlet, compresses that water and feeds it to the outlet. The driven wheel of the vehicle has the form of an impeller operable to draw water into the guide and feed it to the outlet means. The guide is formed in two parts on opposed sides of the wheel, the first part having one or more apertures opening forwardly of the direction of movement of the vehicle and forming inlet means whilst the second part has a jet rearwardly and upwardly of the direction of forward movement of the vehicle. Each part is formed with means providing a seal between it and the rim of the driven wheel. The parts are carried with the driven wheel. The vehicle described is motor tricycle having a pair of front wheels and a single rear driven wheel. The front wheels ( ) of the vehicle have mud guards ( ) which when in water may be rotated to underlie the vehicle wheels and form skies to ease the forward movement of the vehicle through the water. Running boards ( ) extend rearwardly of the mud guards to help in planing. The second part of the guide arrangement has an outlet coupled to a number, six, steering jets mounted on the body of the vehicle.

Amphibious vehicles

Method for treating multiple sclerosis

Growing community of inventors

London, United Kingdom

David Baker