Iomet Pharma Ltd.

Merck Sharp + Dohme Corp.

Other

Alan Wise

Hua Zhou

Yongxin Han

Kun Liu

Hongjun Zhang

Yongqi Deng

Meredeth Ann McGowan

Qinglin Pu

David Jonathan Bennett

Phillip Martin Cowley

Susan Davis

Michael Kiczun

Margaret Huggett

Thomas James Brown

Meredeth A Mcgowan

Bill Hunter

Stuart McElroy

Phillip Cowley

Phillip M Cowley

Philip Cowley

Thomas J Brown

Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises formula (I) wherein X, and Xmay be the same or different and each is independently selected from C, N, O and S; X, X, X, and Xmay be the same or different and each is independently selected from C and N; each bond represented by a dotted line may be present or absent, provided that at least one such bond is present; R, R, R, R, Rand Rmay be present or absent and may be the same or different and each is independently selected from H and a substituted or unsubstituted organic group, provided that the number of R, R, R, R, Rand Rgroups present is such that the respective valencies of X, X, X, X, X, and Xare maintained; and wherein at least one of Rand Rcomprises a group Y, wherein Y is a group having a formula selected from (II), (III), (IV), (V), (VI), (VII) wherein L may be present or absent, and may be a substituted or unsubstituted organic linking group; Rand Rmay be the same or different and are selected from H and a substituted or unsubstituted organic group; each Rmay be the same or different and is selected from H and a substituted or unsubstituted organic group; Ris selected from a substituted or unsubstituted alcohol group or ether group; each Rmay be the same or different and is selected from H and a substituted or unsubstituted organic group; Xmay be selected from C and N; X, X, X, X, X, X, X, Xand Xmay be the same or different and each is independently selected from C, N, O and S; each bond represented by a dotted line may be present or absent; and each Rmay be the same or different and is selected from H and a substituted or unsubstituted organic group. 

Pharmaceutical compound

Disclosed herein are substituted imidazopyridine compounds of formula (I) which are inhibitors of indoleamine 2,3-dioxygenase (IDO) and/or tryptophan-2,3-dioxygenase (TDO) enzymes: (I). Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO- and/or TDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO- and/or TDO-associated disease or disorder. 

Substituted imidazopyridine compounds as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan-2,3-dioxygenase

Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula: wherein X, X, X, X, and Xmay be the same or different and each is independently selected from C, N and O; each atom having a dotted line may independently have a double bond or a single bond, provided that valencies at each atom are maintained; each R, R, R, R, and Rmay be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valencies of X, X, X, X, and Xare maintained; one or two Rgroups may be present and are selected from H and a substituted or unsubstituted organic group, provided that the number of Rgroups present is such that the valency of the carbon atom to which they are attached is maintained, and provided that at least one Ris an organic group comprising an atom double-bonded to an oxygen atom (preferably a carbonyl group or a sulphonyl group) at an &#x3b1;-, &#x3b2;-, or &#x3b3;-position to the carbon atom to which the Ris attached and in which the atom double-bonded to an oxygen atom is also bonded to a hetero-atom. 

Indole derivatives for use in medicine

Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the general formula (I) detailed within. 

Substituted bicyclic fused ring compounds as indoleamine-2,3-dioxygenase inhibitors

Provided is a compound for use in medicine for inhibiting tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO), which compound comprises formula (I) wherein X, X, and X, may be the same or different and each is independently selected from C and N; X, X, X, and Xmay be the same or different and each is independently selected from C, N, O and S wherein when Xis N it has a double bond and wherein when Xis N it has a double bond; the dotted line is a bond which may be present or absent; R, R, R, R, R, R, and Rmay be present or absent and may be the same or different and each is independently selected from H and a substituted or unsubstituted organic group, provided that at least one of R, R, Rand Rcomprises a group Y; and provided that the number of R, R, R, R, R, R, and Rgroups present is such that the respective valencies of X, X, X, X, X, X, and Xare maintained; and wherein Y is a group having a formula selected from (II), (III), (IV), (V) wherein L may be present or absent, and may be a substituted or unsubstituted organic linking group, and Rand Rmay be the same or different and are selected from H and a substituted or unsubstituted organic group, Xis selected from C and N, and each Rmay be the same or different and is selected from H and a substituted or unsubstituted organic group. 

Inhibitors of tryptophan-2,3-dioxygenase or indoleamine-2,3-dioxygenase

Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula: wherein X, X, X, X, and Xmay be the same or different and each is independently selected from C, N and O; each atom having a dotted line may independently have a double bond or a single bond, provided that valencies at each atom are maintained; each R, R, R, R, R, and Rmay be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valencies of X, X, X, X, and Xare maintained; one or two Rgroups may be present and are selected from H and a substituted or unsubstituted organic group, provided that the number of Rgroups present is such that the valency of the carbon atom to which they are attached is maintained, and provided that at least one Ris an organic group comprising an atom double-bonded to an oxygen atom (preferably a carbonyl group or a sulphonyl group) at an &#x3b1;-, &#x3b2;-, or &#x3b3;-position to the carbon atom to which the Ris attached and in which the atom double-bonded to an oxygen atom is also bonded to a hetero-atom. 

Provided is a high-throughput coupled enzyme method of screening for a tryptophan-2,3-dioxygenase (TDO) inhibitor compound and/or an indoleamine-2,3-dioxygenase (IDO) inhibitor compound, which method comprises: (a) reacting tryptophan with isolated IDO and/or isolated TDO in the presence of a test compound to form N-formylkynurenine; (b) reacting N-formylkynurenine from step (a) with isolated kynurenine formamidase to form kynurenine; and (c) detecting the kynurenine produced in step (b) and determining whether the test compound is a TDO and/or an IDO inhibitor compound or not from the presence or absence or quantity of the detected kynurenine, wherein step (a) is conducted in the presence of a reducing system suitable for converting IDO and/or TDO from the Feto the Festate, and which does not prevent the formation of kynurenine in step (c).

Screening method

Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula (I): wherein Xis selected from C and N; Xand Xmay be the same or different and each is independently selected from C, N, O and S; Y is selected from N and O; Z is selected from C, N and O; each bond represented by a dotted line may independently be a double bond or a single bond, provided that valencies at each ring atom are maintained and provided that the ring Q contains at least one double bond and provided that the atom N has a double bond; Rand Rmay be present or absent and may be the same or different and each is independently selected from H and a substituted or unsubstituted organic group, provided that the number of Rgroups present is such that the valency of Xis maintained, and the number of Rgroups present is such that the valency of Xis maintained; each Rand Rmay be present or absent and may be the same or different and each is independently selected from H and a substituted or unsubstituted organic group, provided that the number of Rand Rgroups present is such that the valency of Z is maintained; Ris selected from H and a substituted or unsubstituted organic group; Rmay be present or absent and is selected from H and a substituted or unsubstituted organic group; and Cy is a cyclic organic group. 

Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula: wherein X, X, X, and Xmay be the same or different and each is independently selected from C and N; X, X, X, X, X, X, and Xmay be the same or different and each is independently selected from C, N and O; each bond having a dotted line may independently be a double bond or a single bond, provided that valencies at each atom are maintained; the dotted lines joining Xwith the carbon atoms either side of Xare single bonds, and are only present when Xis absent, Xis absent and Xis C, and when these bonds are present the ring carbons on each side of Xare not directly bonded to each other; each Rmay be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of Rgroups present is such that the valency of Xis maintained; each R, R, R, R, Rand Rmay be present or absent and may be the same or different and each is independently selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valency of the ring carbon atoms is maintained; Rmay be present or absent and is selected from H and a substituted or unsubstituted organic group, provided that the number of Rgroups present is such that the valency of Xis maintained; each Rmay be present or absent and may be the same or different and is independently selected from H and a substituted or unsubstituted organic group, provided that the number of Rgroups present is such that the valency of Xis maintained; each R, R, R, and Rmay be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valencies of X, X, X, and Xare maintained; each R, Rand Rmay be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valencies of X, X, and Xare maintained; and Ris selected from H and a substituted or unsubstituted organic group, preferably H and a substituted or unsubstituted C-Calkyl group; and wherein any R group may form a ring with any other R group on an adjacent and/or proximal atom.

Growing community of inventors

Edinburgh, United Kingdom

Alan Wise