Abstract: Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R1, is a group of formula (IA): —Ar1-(Alk1)p-(Z)r-(Alk2)s-Q, wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1 and Alk2 are optionally substituted divalent C1-C6 alkylene or C2-C6 alkenylene radicals, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C?O)—, —(C?S)—, —SO2—, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)—, —NRASO2— or —NRA— wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk1)p-(Z)r-(Alk2)s-Q wherein Q, Alk1, Alk2, Z, p, r and s are as defined above in relation to group (IA); and

Abstract: The present invention relates to new salt forms of 5-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide, in particular the mesylate, hydrochloride, tartrate, phosphate and hemi fumarate salt thereof; to crystalline forms of such salts; to polymorphs of 5-(2,4-dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide; to hydrates and polymorphs of the new salt forms mentioned above; to the use of the new salt forms mentioned above for the manufacture of a medicament for the treatment of a disorder mediated by Hsp90; to a method for treating a disorder mediated by Hsp90 using the new salt forms; to formulations comprising such salt forms, in particular aqueous solutions suitable for intravenous administration; and to amber glass containers being filled with such formulations.

Abstract: Compounds of formula (I) are inhibitors of HSP90 activity, and useful in the treatment of proliferative disease such as cancers: wherein R1, R2 and R3 are as defined in the specification, and X is —OR4 or —NR4R5 wherein R4 and R5 independently represent hydrogen or optionally substituted C1-C6 alkyl, or R4 and R5 taken together with the nitrogen to which they are attached form an optionally substituted nitrogen-containing ring having 5-8 ring atoms.

Abstract: Compounds of formula (IA) or (IB) or a salt, N-oxide, hydrate or solvate thereof are inhibitors of HSP90, and are of value in the treatment of diseases responsive to HSP90 inhibition such as cancers.

Abstract: Compounds of formula (I) have HSP90 inhibitory activity and are therefore useful in the treatment of, inter alia, cancer: Formula (I) wherein Ri is hydrogen, fluoro, chloro, bromo, or a radical of formula -X-Alk1-(Z)m-(Alk2)n-Q wherein X is —O—, —S— —S(O)—, SO2—, or —NH—, Z is —O—, —S—, —(C?O)—, —(C?S)—, —S(O)—, —SO2—, —NRA—, or, in either orientation —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)—, or —NRASO2— wherein RA is hydrogen or C1-C6 alkyl AIk1 and AIk2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, n and p are independently 0 or 1, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is a radical of formula —(Ar1)p-(Alk1)q-(Z)r-(Alk2)s-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1, Alk2, Z, and Q are as defined above, and p, q, r and s are independently 0 or 1; and R3 is cyano (—CN), fluoro, chloro, bromo, methyl in which in which one or more hydrogen atoms are optionally replaced by fluorine

Abstract: Compounds of formula (I) are inhibitors of PDK1 and CHK1 activity, and of use in the treatment of cancer and autoimmune disorders (I): wherein R2 is a radical of formula R7—(CH2)n?, or a radical of formula -Alk-N(—R5)—R9 wherein n is 0, 1, 2 or 3 and Alk is C1-C6 alkylene; R7 is (i) a heterocyclic ring of 5 or 6 ring atoms coupled via a ring carbon wherein the sole heteroatom is nitrogen, optionally substituted by C1-C6 alkyl or aryl C1-C6 alkyl, (ii) 1-aza-bicyclo[2.2.2]oct-3-yl, or (iii) 8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl; R8 and R9 are independently selected from hydrogen or C1-C3 alkyl; and the remaining substituents are as defined in the claims.

Abstract: Compounds of formula (I) are inhibitors of HSP90, and useful in the treatment of, for example, cancers: wherein R2 is a group of formula (IA): -(Ar1)m-(Alk1)p-(Z)r-(Alk2)s-Q??(IA) wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1 and Alk2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C?O)—, —(C?S)—, —SO2—, —C(?O)O—, —C(?O)NRA—, —C(?S)NRA—, —SO2NRA—, —NRAC(?O)—, —NRASO2— or —NRA— wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C6)alkyl, aryl or heteroaryl radical; and R4 is (i) hydrogen, a —CN group, a nitro group —NO2, or a —C(?NOH)(NH2) group, or (ii) an optionally substituted C1-C6alkyl, aryl, heterocyclic, aryl(C1-C6alkyl)-, or heterocyclic(C1-C6alkyl)- group, or (iii) a group of formula —C(?O)R5 wherein R5 is

Abstract: Compounds of formula (I) are HSP90 inhibitors, of utility in the treatment of, for example, cancers: wherein R1 is -(Alk1)p-(Z)r(Alk2)-Q wherein AIk1 and AIk2 are optionally substituted divalent C1C3 alkylene or C2-C3 alkenylene radicals, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C?O)—, —(C?S)—, —SO2—, —C(?O)O—, —C(?O)NRA, —C(?S)NRA-, —SO2NRA—NRAC(?O)—, —NRASO2— or —NRA— wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is optionally substituted aryl or heteroaryl; R3 is hydrogen, an optional substituent, or an optionally substituted (C1-C-6)alkyl, aryl or heteroaryl radical; and R4 is (i) a carboxylic ester, carboxamide or sulfonamide group, or (ii) a —CN group, or (iii) an optionally substituted C1-C6alkyl, aryl, heteroaryl, aryl(C1-C6alkyl)-, or heteroaryl(C1-C6alkyl)- group, or (iv) a group of formula —C(?O)R5 wherein R5 is hydroxyl, optionally substituted C1-C6alkyl, C1-C6alkyoxy, aryl, aryloxy, heteroaryl, heteroaryl

Abstract: The present invention pertains to the use of certain 3,4-diarylpyazoles of formula (I), both in vitro and in vivo, to inhibit heat shock protein 90 (HSP90), and in the treatment of conditions mediated by HSP90, including, for example, cancer; wherein: Ar3 is independently: a C5-20aryl group, and is optionally substituted; Ar4 is independently: a C5-20aryl group, and is optionally substituted; R5 is independently: hydrogen; halo; hydroxyl; ether; formyl; acyl; carboxy; ester; acyloxy; oxycarbonyloxy; amido; acylamido; aminocarbonyloxy; tetrazolyl; amino; nitro; cyano; azido; sulfhydryl; thioether; sulfonamide; C1-7alkyl; C3-20heterocycyl; or C5-20aryl; R<SP>N</SP> is independently: —H; C1-7alkyl; C3-20heterocycyl; or, C5-20aryl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof.

Abstract: The present invention relates to novel amidino compound of formula (I): to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use as selective inhibitors of inducible nitric oxide synthase.

Abstract: The present invention relates to novel amidino compound of formula (I). to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use as selective inhibitors of inducible nitric oxide synthase.

Abstract: The present invention relates to novel amidino compound of formula (I).

Abstract: A compound of formula (I) ##STR1## wherein R.sup.1 is a C.sub.1-6 straight or branched chain alkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, a C.sub.3-6 cycloalkyl group or a C.sub.3-6 cycloalkylC.sub.1-6 alkyl group, each optionally substituted by one to three groups independently selected from: --CN; --NO.sub.2 ; a group --COR.sup.2 wherein R.sup.2 is hydrogen, C.sub.1-6 alkyl, --OR.sup.3 wherein R.sup.3 is hydrogen or C.sub.1-6 alkyl or NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are independently selected from hydrogen or C.sub.1-6 alkyl; a group --S(O).sub.m R.sup.6 wherein m is 0, 1 or 2, R.sup.6 is hydrogen, C.sub.1-6 alkyl, hydroxy or NR.sup.7 R.sup.8 wherein R.sup.7 and R.sup.8 are independently hydrogen or C.sub.1-6 alkyl; a group PO(OR.sup.9).sub.2 wherein R.sup.9 is hydrogen or C.sub.1-6 alkyl; a group NR.sup.10 R.sup.11 wherein R.sup.10 and R.sup.11 are independently selected from hydrogen, C.sub.1-6 alkyl, --COR.sup.12 wherein R.sup.12 is hydrogen or C.sub.

Abstract: A compound of formula (I) wherein R1 is a C1-6 straight or branched chain alkyl group, a C2-6alkenyl group, a C2-6 alkynyl group, a C3-6cycloalkyl group or a C3-6cycloalkylC1-6alkyl group, each optionally substituted by one to three groups independently selected from: —CN; —NO2; a group —COR2 wherein R2 is hydrogen, C1-6 alkyl, —OR3 wherein R3 is hydrogen or C1-6alkyl or NR4R5 wherein R4 and R5 are independently selected from hydrogen or C1-6 alkyl; a group —S(O)mR6 wherein m is 0, 1 or 2, R6 is hydrogen, C1-6 alkyl, hydroxy or NR7R8 wherein R7 and R8 are independently hydrogen or C1-6 alkyl; a group PO(OR9)2 wherein R9 is hydrogen or C1-6 alkyl; a group NR10R11 wherein R10 and R11 are independently selected from hydrogen, C1-6 alkyl, —COR12 wherein R12 is hydrogen or C1-6 alkyl, or —S(O)m?R13 wherein m? is 0, 1 or 2 and R13 is hydrogen or C1-6 alkyl; halo; or a group —OR14 wherein R14 is hydrogen, C1-6 alkyl optionally substituted by one to three halo atoms, C6-10 aryl or —COR15 wherein R15 is hydroge