Abstract: The present application relates to cyclosporine analogues and their use in medical applications, including as antiviral compounds and in gene therapy.

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

Abstract: The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of cardiovascular disease or of an inflammatory disease or condition: wherein: V is N or CR3; X is N or CR4; Y is N or CR5; Z is N or CR6; B is —(C?O)R1, a 5- to 10-membered heteroaryl group, or a group L??-NRR?, wherein R and R? are the same or different and each represents a hydrogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group; R1 is a 5- to 10-membered heterocyclyl group, or —OR?, wherein R? is a hydrogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, or R1 is a proteinogenic ? amino acid, which is linked to the carbonyl moiety in the compound of formula (I) via the ? amino group, which amino acid is optionally esterified at the ? carboxylic acid group with a C1-C6 alkyl group or a C6-C10 aryl group, or R1 is —NR?R??, —NRIV-L??-CONR?R??, or —NRIV-L??-COOR, wherein R, R?, R?? and RIV are the same or different and e

Abstract: The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein: Z is OR16 or NR17R18; R16 is H or alkyl; R17 is H or alkyl; R18 is alkyl or cycloalkyl, each of which is optionally substituted by one or more substituents selected from OH, halogen and COOR11; X is a group selected from —C?C—<CH2)p—; —C<R5)?C(R6)—(CH2)q—; and —C(R5)(R6)C(R7)(R8)—(CH2)2—; where each of R5, R6, R7 and R8 is independently II or alkyl, and each of p, q and r is independently 1, 2, 3, 4 or 5; Y is a group selected from: CN; COOR2; CONR3R4; SO2NR9R10; NR12COR13; NR14SO2R15; and a heterocyclic group selected from oxadiazolyl, thiazolyl, iso- thiazolyl, oxazolyl, iso-oxazolyl, pyrazoiyl and it-nidazolyl; where each of R2, R3 and R4 is independently H or alkyl; or R3 and R4 are linked, together with the nitrogen to which they are attached, to form a 5 or 6-membered heterocycloalkyl or heterocycloalkenyl group, said heterocycloalkyl or heterocycloalkenyl group opt

Abstract: The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt thereof: (I) wherein: n is 0 or 1; R1 is selected from H, alkyl and aralkyl, wherein said alkyl and aralkyl groups may be optionally substituted by one or more OH groups; X is a group selected from —C?C—(CH2)p—; —C(R5)?C(R6)—(CH2)q—; and —C(R5)(R6)C(R7)(R8)—(CH2)r-; where each of R5, R6, R7 and R8 is independently H or alkyl, and each of p, q and r is independently 1, 2, 3, 4 or 5; Y is a group selected from: CN; COOR2; CONR3R4; SO2NR9R10; NR12COR13; NR14SO2R15; and a heterocyclic group selected from oxadiazolyl, thiazolyl, iso-thiazolyl, oxazolyl, iso-oxazolyl, pyrazolyl and imidazolyl; where each of R2, R3 and R4 is independently H or alkyl; or R3 and R4 are linked, together with the nitrogen to which they are attached, to form a 5 or 6-membered heterocycloalkyl or heterocycloalkenyl group, said heterocycloalkyl or heterocycloalkenyl group optionally containing one or more further groups selected from O, N, CO an

Abstract: The present invention relates to BKCa activators for use in the treatment of a muscular disorder, or for controlling spasticity or tremors, for example, spasticity in MS.

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

Abstract: A cyclosporin derivative which is a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a viral infection: wherein: A represents B represents methyl or ethyl, R2 represents ethyl or isopropyl, R4 represents —CH2CH(CH3)CH3, —CH2CH(CH3)CH2CH3, —CH(CH3)CH3 or —CH(CH3)CH2CH3, and either (a) one of R1 and R1* represents hydrogen and the other represents methyl, and R3 represents -L3-G3, or (b) one of R1 and R1* represents hydrogen and the other represents -L1-G1, and R3 represents H, wherein L1 and L3 represent a direct bond, a C1-C6 alkylene group or a C2-C6 alkenylene group; and G1 and G3 represent a hydrogen atom, a —COOR? group, or a phenyl moiety which is unsubstituted or substituted by one, two or three substituents selected from a halogen atom, a —COOR? group, a —CONR?R? group, a hydroxyl group, a C1-C6 alkyl group and a C1-C6 alkoxy group, wherein R? and R? are the same or different and represent hydrogen or a C1-C6 alkyl group,

Abstract: The present invention relates to a compound of formula (I) in crystalline form, wherein said compound is in the form of the free base or a pharmaceutically acceptable salt thereof, or a solvate of the free base or salt form thereof. The invention also relates to a pharmaceutical composition containing said crystalline form as an active ingredient, and use thereof in the prevention or treatment of disease. The invention further relates to a process for preparing the crystalline form.

Abstract: The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of cardiovascular disease or of an inflammatory disease or condition: wherein: V is N or CR3; X is N or CR4; Y is N or CR5; Z is N or CR6; B is —(C?O)R1, a 5- to 10-membered heteroaryl group, or a group -L??-NRR?, wherein R and R? are the same or different and each represents a hydrogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group; R1 is a 5- to 10-membered heterocyclyl group, or —OR?, wherein R? is a hydrogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, or R1 is a proteinogenic ? amino acid, which is linked to the carbonyl moiety in the compound of formula (I) via the ? amino group, which amino acid is optionally esterified at the ? carboxylic acid group with a C1-C6 alkyl group or a C6-C10 aryl group, or R1 is —NR?R??, —NRIV-L??-CONR?R??, or —NRIV-L??-COOR, wherein R, R?, R?? and RIV are the same or different and ea

Abstract: The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt thereof : (I) wherein: n is 0 or 1; R1 is selected from H, alkyl and aralkyl, wherein said alkyl and aralkyl groups may be optionally substituted by one or more OH groups; X is a group selected from —C?C—(CH2)p—; —C(R5)?C(R6)—(CH2)q—; and —C(R5)(R6)C(R7)(R8)—(CH2)r—; where each of R5, R6, R7 and is independently II or alkyl, and each of p, q and r is independently 1, 2, 3, 4 or 5; Y is a group selected from: CN; COOR2; CONR3R4; SO2NR9R10; NR12COR13; NR14SO2R15; and a heterocyclic group selected from oxadiazolyl, thiazolyl, isothiazolyl, oxazolyl, iso-oxazolyl, pyrazolyl and imidazolyl; where each of R2, R3 and R4 is independently H or alkyl; or R3 and R4 are linked, together with the nitrogen to which they are attached, to form a 5 or 6-membered heterocycloalkyl or heterocycloalkenyl group, said heterocycloalkyl or heterocycloalkenyl group optionally containing one or more further groups selected from O, N, CO and

Abstract: The present disclosure relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Z is selected from OH, NHCH2CH2F, NHCH(Me)CH2OH and NHCH2CH2OH; X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO2-alkyl, alkenyl, CN, NH2, hydroxy, halo, alkoxy, CF3 and nitro; Y is a polar functional group selected from OH, NO2, CN, COR3, COOR3, NR3R4, CONR3R4, SO3H, SO2—R3, SO2NR3R4 and CF3, where each of R3 and R4 is independently H or a hydrocarbyl group; A is phenyl or pyridyl; and B is (CH2)n where n is 0; with the proviso that: (i) when A is phenyl, and Z is OH, X—Y is other than C?C—(CH2)2CO2H, C?C—(CH2)2CO2Me, (CH2)4CO2H. Uses of such compounds as medicaments for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors are provided.

Abstract: A cyclosporin derivative which is a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a viral infection: wherein: A represents (F(II)) or (F(III)) B represents methyl or ethyl, R2 represents ethyl or isopropyl, R4 represents —CH2CH(CH3)CH3, —CH2CH(CH3)CH2CH3, —CH(CH3)CH3 or —CH(CH3)CH2CH3, and either (a) one of R1 and R1* represents hydrogen and the other represents methyl, and R3 represents —L3-G3, or (b) one of R1 and R1* represents hydrogen and the other represents and R3 represents H, wherein L1 and L3 represent a direct bond, a C1-C6 alkylene group or a C2-C6 alkenylene group; and G1 and G3 represent a hydrogen atom, a —COOR? group, or a phenyl moiety which is unsubstituted or substituted by one, two or three substituents selected from a halogen atom, a —COOR? group, a —CONR?R? group, a hydroxyl group, a C1-C6 alkyl group and a C1-C6 alkoxy group, wherein R? and R? are the same or different and represent hydrogen or a C1-C6 alkyl group, prov

Abstract: The present invention relates to a compound of formula (I) in crystalline form, wherein said compound is in the form of the free base or a pharmaceutically acceptable salt thereof, or a solvate of the free base or salt form thereof. The invention also relates to a pharmaceutical composition containing said crystalline form as an active ingredient, and use thereof in the prevention or treatment of disease. The invention further relates to a process for preparing the crystalline form.

Abstract: The present disclosure relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Z is selected from OH, NHCH2CH2F, NHCH(Me)CH2OH and NHCH2CH2OH; X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO2-alkyl, alkenyl, CN, NH2, hydroxy, halo, alkoxy, CF3 and nitro; Y is a polar functional group selected from OH, NO2, CN, COR3, COOR3, NR3R4, CONR3R4, SO3H, SO2—R3, SO2NR3R4 and CF3, where each of R3 and R4 is independently H or a hydrocarbyl group; A is phenyl or pyridyl; and B is (CH2)n where n is 0; with the proviso that: (i) when A is phenyl, and Z is OH, X—Y is other than C?C—(CH2)2CO2H, C?C—(CH2)2CO2Me, (CH2)4CO2H. Uses of such compounds as medicaments for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors are provided.

Abstract: The present invention relates to a process for preparing a compound of formula wherein: R2 is cycloalkyl or alkyl, each of which may be optionally substituted; Y is —CONR3R4, —CN or CO2R5; R3, R4 and R5 are each independently H or alkyl; n is 1 to 6; wherein said process comprising the steps of: (i) treating a compound of formula (IV), where R1 is alkyl, with a compound of formula (V) and forming a compound of formula (IIIb); (ii) treating said compound of formula (IIIb) with a compound of formula (I1) to form a compound of formula (I).

Abstract: A conjugate which comprises a cyclosporin moiety of formula (I) linked to one or more mitochondrial targeting groups, or a pharmaceutically acceptable salt thereof: wherein: A represents or, B represents methyl or ethyl, one Of R1 and R1* represents hydrogen and the other represents methyl, R2 represents ethyl or isopropyl, R3 represents hydrogen or methyl, and R4 represents —CH2CH(CH3)CH3, —CH2CH(CH3)CH2CH3, —CH(CH3)CH3 or —CH(CH3)CH2CH3.

Abstract: The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof,

Abstract: The invention provides an indazole derivative of formula (1), or a pharmaceutically acceptable salt or N-oxide thereof, wherein R1, R2, R3 and R4 are as defined herein. The indazole derivatives are capable of blockading voltage dependent sodium channels and they are useful in the treatment or prevention of normal tension glaucoma, multiple sclerosis, a motorneurone disease, stroke, spinal cord injury, Alzheimer's disease, Parkinson's disease or pain.

Abstract: The present invention is a compound of formula (I) or formula (II) which are suitable as NP-1 antagonists.