公开(公告)号：US20200230117A1

公开(公告)日：2020-07-23

申请号：US16088873

申请日：2017-04-24

申请人： Phillip M. COWLEY ,  Meredeth Ann MCGOWAN ,  Thomas J. BROWN ,  WISE Alan ,  Hua ZHOU ,  Yongxin HAN ,  Kun LIU ,  Qinglin PU ,  Hongjun ZHANG ,  IOMet Pharma Ltd.

发明人： Phillip M. Cowley ,  Meredeth Ann McGowan ,  Thomas J. Brown ,  Yongxin Han ,  Kun Liu ,  Qinglin Pu ,  Alan Wise ,  Hongjun Zhang ,  Hua Zhou

IPC分类号： A61K31/438 ,  C07D519/00

摘要： 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.

公开(公告)号：US20160367564A1

公开(公告)日：2016-12-22

申请号：US15100494

申请日：2014-12-02

申请人： IOMET PHARMA LTD

发明人： Phillip Martin Cowley ,  Alan Wise ,  Margaret Huggett

IPC分类号： A61K31/551 ,  C07D401/04 ,  A61K31/454 ,  C07D401/14 ,  C07D471/04 ,  A61K31/4545 ,  A61K31/4439 ,  C07D413/14 ,  C07D409/14 ,  A61K31/444 ,  C07D405/14 ,  A61K31/4725 ,  C07D209/40 ,  A61K31/496 ,  A61K31/498 ,  C07D403/04 ,  A61K31/404 ,  C07D471/10 ,  A61K31/435 ,  C07D401/06 ,  C07D209/20 ,  C07D403/06 ,  A61K31/55 ,  A61K31/506 ,  C07D487/04 ,  A61K31/4985 ,  A61K31/5377 ,  A61K31/497 ,  C07D513/04 ,  A61K45/06

CPC分类号： A61K31/551 ,  A61K31/404 ,  A61K31/435 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  C07D209/20 ,  C07D209/34 ,  C07D209/40 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D513/04

摘要： 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 X2, X4, X10, and X11 may be the same or different and each is independently selected from C and N; X1, X3, X5, X6, X7, X8, and X9 may 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 X4 with the carbon atoms either side of X2 are single bonds, and are only present when X2 is absent, X3 is absent and X4 is C, and when these bonds are present the ring carbons on each side of X2 are not directly bonded to each other; each R1 may 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 R1 groups present is such that the valency of X1 is maintained; each R12, R13, R13′, R14, R15 and R15′ may 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; R16 may be present or absent and is selected from H and a substituted or unsubstituted organic group, provided that the number of R16 groups present is such that the valency of X2 is maintained; each R17 may 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 R17 groups present is such that the valency of X3 is maintained; each R2, R3, R4, and R5 may 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 X6, X7, X8, and X9 are maintained; each R7, R8 and R9 may 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 X10, X11, and X5 are maintained; and R6 is selected from H and a substituted or unsubstituted organic group, preferably H and a substituted or unsubstituted C1-C6 alkyl group; and wherein any R group may form a ring with any other R group on an adjacent and/or proximal atom.

公开(公告)号：US10287252B2

公开(公告)日：2019-05-14

申请号：US15524148

申请日：2015-11-02

申请人： IOmet Pharma Ltd.

发明人： Phillip M. Cowley ,  Alan Wise ,  Susan Davis ,  Margaret Huggett ,  Michael Kiczun

IPC分类号： C07D237/28 ,  A61K31/472 ,  A61K31/4725 ,  A61K31/502 ,  A61K45/06 ,  C07D217/02 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12

摘要： 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 X1, X2, and X7, may be the same or different and each is independently selected from C and N; X3, X4, X5, and X6 may be the same or different and each is independently selected from C, N, O and S wherein when X3 is N it has a double bond and wherein when X6 is N it has a double bond; the dotted line is a bond which may be present or absent; R1, R2, R3, R4, R5, R6, and R7 may 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 R2, R3, R4 and R6 comprises a group Y; and provided that the number of R1, R2, R3, R4, R5, R6, and R7 groups present is such that the respective valencies of X1, X2, X3, X4, X5, X6, and X7 are 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 R31 and R32 may be the same or different and are selected from H and a substituted or unsubstituted organic group, X8 is selected from C and N, and each R313 may be the same or different and is selected from H and a substituted or unsubstituted organic group.

公开(公告)号：US10858319B2

公开(公告)日：2020-12-08

申请号：US16190334

申请日：2018-11-14

申请人： IOMet Pharma Ltd.

发明人： Phillip M. Cowley ,  Alan Wise ,  Michael Kiczun ,  Susan Davis

IPC分类号： C07D401/12 ,  C07D209/42 ,  A61K45/06 ,  C07D263/58 ,  C07D403/12 ,  C07D405/12 ,  C07D471/04 ,  C07D409/12 ,  C07D405/14 ,  C07D413/12 ,  C07D417/12 ,  A61K31/4155 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/475 ,  A61K31/496 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/437 ,  A61K31/4355 ,  A61K31/424 ,  A61K31/423 ,  A61K31/4188 ,  A61K31/4184 ,  A61K31/407 ,  A61K31/405 ,  A61K31/4045 ,  A61K31/404

摘要： 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 X1, X2, X3, X4, and X5 may 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 R1, R2, R3, R4, and R7 may 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 X1, X2, X3, X4, and X5 are maintained; one or two R6 groups may be present and are selected from H and a substituted or unsubstituted organic group, provided that the number of R6 groups present is such that the valency of the carbon atom to which they are attached is maintained, and provided that at least one R6 is an organic group comprising an atom double-bonded to an oxygen atom (preferably a carbonyl group or a sulphonyl group) at an α-, β-, or γ-position to the carbon atom to which the R6 is attached and in which the atom double-bonded to an oxygen atom is also bonded to a hetero-atom.

公开(公告)号：US09931347B2

公开(公告)日：2018-04-03

申请号：US15100494

申请日：2014-12-02

申请人： IOmet Pharma Ltd.

发明人： Phillip Martin Cowley ,  Alan Wise ,  Margaret Huggett

IPC分类号： A61K31/551 ,  A61K31/404 ,  C07D401/04 ,  C07D403/12 ,  C07D401/12 ,  C07D403/04 ,  C07D405/12 ,  C07D413/12 ,  C07D471/04 ,  C07D487/04 ,  C07D209/34 ,  C07D209/40 ,  C07D513/04 ,  A61K31/435 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  C07D209/20 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/10

CPC分类号： A61K31/551 ,  A61K31/404 ,  A61K31/435 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  C07D209/20 ,  C07D209/34 ,  C07D209/40 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D513/04

摘要： 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 X2, X4, X10, and X11 may be the same or different and each is independently selected from C and N; X1, X3, X5, X6, X7, X8, and X9 may 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 X4 with the carbon atoms either side of X2 are single bonds, and are only present when X2 is absent, X3 is absent and X4 is C, and when these bonds are present the ring carbons on each side of X2 are not directly bonded to each other; each R1 may 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 R1 groups present is such that the valency of X1 is maintained; each R12, R13, R13′, R14, R15 and R15′ may 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; R16 may be present or absent and is selected from H and a substituted or unsubstituted organic group, provided that the number of R16 groups present is such that the valency of X2 is maintained; each R17 may 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 R17 groups present is such that the valency of X3 is maintained; each R2, R3, R4, and R5 may 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 X6, X7, X8, and X9 are maintained; each R7, R8 and R9 may 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 X10, X11, and X5 are maintained; and R6 is selected from H and a substituted or unsubstituted organic group, preferably H and a substituted or unsubstituted C1-C6 alkyl group; and wherein any R group may form a ring with any other R group on an adjacent and/or proximal atom.

公开(公告)号：US20160120863A1

公开(公告)日：2016-05-05

申请号：US14893513

申请日：2014-05-22

申请人： IOMET PHARMA LTD.

发明人： Phillip Martin Cowley ,  Alan Wise ,  Thomas James Brown ,  Matthew Isherwood ,  Anjan Chakrabarti

IPC分类号： A61K31/496 ,  G01N33/50 ,  A61K45/06 ,  C07D471/04 ,  A61K31/5377

CPC分类号： A61K31/496 ,  A61K31/4985 ,  A61K31/5377 ,  A61K45/06 ,  C07D471/04 ,  C07D487/04 ,  C07D519/00 ,  G01N33/502 ,  G01N2333/705 ,  G01N2500/04 ,  G01N2500/10 ,  Y02A50/385 ,  Y02A50/414 ,  Y02A50/423

摘要： Provided is a SLC2A class I transporter inhibitor compound for use in medicine, which compound comprises the following formula: wherein A and Z may be the same or different and are each independently selected from C, N, O and S; each X may be the same or different and is independently selected from C, N, O and S; R1 and R5 may be present or absent and may be the same or different and are each selected from H and a substituted or unsubstituted organic group; Z completes a ring with each X, each ring comprising from 3 to 8 ring atoms including the X, A, and Z, each ring atom being independently selected from C, N, O and S, and each ring atom being unsubstituted or independently substituted with H or a substituted or unsubstituted organic group; and wherein the bonds between all of the atoms in the rings including the X, A, and Z may independently be single bonds or double bonds, provided that when X or a ring atom is O or S the bonds to X are single bonds.

摘要翻译： 本发明提供一种用于医药的SLC2A I类转运蛋白抑制剂化合物，该化合物包含下式：其中A和Z可以相同或不同，并且各自独立地选自C，N，O和S; 每个X可以相同或不同，并且独立地选自C，N，O和S; R 1和R 5可以存在或不存在，并且可以相同或不同，并且各自选自H和取代或未取代的有机基团; Z与每个X完成一个环，每个环包含3至8个环原子，包括X，A和Z，每个环原子独立地选自C，N，O和S，每个环原子是未取代或独立取代的 与H或取代或未取代的有机基团; 并且其中包括X，A和Z的环中所有原子之间的键可以独立地为单键或双键，条件是当X或环原子为O或S时，与X的键为单键。

公开(公告)号：US11096930B2

公开(公告)日：2021-08-24

申请号：US16088873

申请日：2017-04-24

申请人： IOMet Pharma Ltd.

发明人： Phillip M. Cowley ,  Meredeth Ann McGowan ,  Thomas J. Brown ,  Yongxin Han ,  Kun Liu ,  Qinglin Pu ,  Alan Wise ,  Hongjun Zhang ,  Hua Zhou

IPC分类号： C07D519/00 ,  A61K31/438

摘要： 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.

公开(公告)号：US20200172492A1

公开(公告)日：2020-06-04

申请号：US16780349

申请日：2020-02-03

申请人： IOmet Pharma Ltd.

发明人： Phillip M. Cowley ,  Alan Wise ,  Susan Davis ,  Michael Kiczun

IPC分类号： C07D231/56 ,  A61K31/416 ,  A61K31/454 ,  A61K31/496 ,  C07D401/04 ,  C07D403/04 ,  C07D471/08 ,  C07D471/10 ,  A61K31/445 ,  A61K31/439 ,  C07D417/12 ,  A61K31/4523 ,  A61K31/4985 ,  A61K31/4995 ,  C07D498/08 ,  C07D498/04 ,  C07D487/04 ,  A61K31/438 ,  A61K31/499 ,  C07D471/04 ,  C07D498/10 ,  C07D405/06 ,  C07D401/14 ,  C07D261/20 ,  C07D403/14 ,  C07D403/12 ,  C07D417/14 ,  A61K31/435 ,  A61K31/551 ,  A61K45/06

摘要： 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 X1, and X2 may be the same or different and each is independently selected from C, N, O and S; X3, X4, X5, and X6 may 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; R1, R2, R3, R4, R5 and R6 may 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 R1, R2, R3, R4, R5 and R6 groups present is such that the respective valencies of X1, X2, X3, X4, X5, and X6 are maintained; and wherein at least one of R5 and R6 comprises 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; R31 and R32 may be the same or different and are selected from H and a substituted or unsubstituted organic group; each R34 may be the same or different and is selected from H and a substituted or unsubstituted organic group; R35 is selected from a substituted or unsubstituted alcohol group or ether group; each R36 may be the same or different and is selected from H and a substituted or unsubstituted organic group; X7 may be selected from C and N; X8, X9, X10, X11, X12, X13, X14, X15 and X16 may 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 R313 may be the same or different and is selected from H and a substituted or unsubstituted organic group.

公开(公告)号：US10590086B2

公开(公告)日：2020-03-17

申请号：US15524142

申请日：2015-11-02

申请人： IOmet Pharma Ltd.

发明人： Phillip M. Cowley ,  Alan Wise ,  Susan Davis ,  Michael Kiczun

IPC分类号： A61K31/416 ,  A61K31/454 ,  A61K31/496 ,  A61K31/435 ,  A61K31/551 ,  C07D231/56 ,  C07D401/04 ,  C07D403/04 ,  C07D471/08 ,  C07D471/10 ,  A61K31/445 ,  A61K31/439 ,  C07D417/12 ,  A61K31/4523 ,  A61K31/4985 ,  A61K31/4995 ,  C07D498/08 ,  C07D498/04 ,  C07D487/04 ,  A61K31/438 ,  A61K31/499 ,  C07D471/04 ,  C07D498/10 ,  C07D405/06 ,  C07D401/14 ,  C07D261/20 ,  C07D403/14 ,  C07D403/12 ,  C07D417/14 ,  A61K45/06

摘要： 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 X1, and X2 may be the same or different and each is independently selected from C, N, O and S; X3, X4, X5, and X6 may 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; R1, R2, R3, R4, R5 and R6 may 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 R1, R2, R3, R4, R5 and R6 groups present is such that the respective valencies of X1, X2, X3, X4, X5, and X6 are maintained; and wherein at least one of R5 and R6 comprises 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; R31 and R32 may be the same or different and are selected from H and a substituted or unsubstituted organic group; each R34 may be the same or different and is selected from H and a substituted or unsubstituted organic group; R35 is selected from a substituted or unsubstituted alcohol group or ether group; each R36 may be the same or different and is selected from H and a substituted or unsubstituted organic group; X7 may be selected from C and N; X8, X9, X10, X11, X12, X13, X14, X15 and X16 may 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 R313 may be the same or different and is selected from H and a substituted or unsubstituted organic group.

公开(公告)号：US10155972B2

公开(公告)日：2018-12-18

申请号：US15105615

申请日：2014-12-18

申请人： IOmet Pharma Ltd.

发明人： Bill Hunter ,  Stuart McElroy ,  Alan Wise

IPC分类号： C12Q1/26 ,  C12Q1/48

摘要： 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 Fe3+ to the Fe2+ state, and which does not prevent the formation of kynurenine in step (c).