PHARMACEUTICAL COMPOUND
20170267668 · 2017-09-21
Assignee
Inventors
Cpc classification
C07D257/06
CHEMISTRY; METALLURGY
A61P31/00
HUMAN NECESSITIES
C07D413/04
CHEMISTRY; METALLURGY
A61K31/44
HUMAN NECESSITIES
A61K31/41
HUMAN NECESSITIES
A61K31/4439
HUMAN NECESSITIES
A61K31/4155
HUMAN NECESSITIES
A61K31/454
HUMAN NECESSITIES
C07D413/12
CHEMISTRY; METALLURGY
A61P15/00
HUMAN NECESSITIES
A61P35/00
HUMAN NECESSITIES
International classification
C07D413/12
CHEMISTRY; METALLURGY
C07D413/04
CHEMISTRY; METALLURGY
A61K31/454
HUMAN NECESSITIES
A61K31/4155
HUMAN NECESSITIES
C07D257/06
CHEMISTRY; METALLURGY
A61K31/41
HUMAN NECESSITIES
A61K31/4439
HUMAN NECESSITIES
Abstract
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 X.sup.1 is selected from C and N; X.sup.3 and X.sup.5 may 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; R.sup.3 and R.sup.5 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 R.sup.3 groups present is such that the valency of X.sup.3 is maintained, and the number of R.sup.5 groups present is such that the valency of X.sup.5 is maintained; each R.sup.11 and R.sup.12 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 R.sup.11 and R.sup.12 groups present is such that the valency of Z is maintained; R.sup.21 is selected from H and a substituted or unsubstituted organic group; R.sup.22 may be present or absent and is selected from H and a substituted or unsubstituted organic group; and Cy is a cyclic organic group.
##STR00001##
Claims
1. A compound having the following formula, or a pharmaceutically acceptable salt thereof: ##STR00042## wherein: X.sup.1 is selected from C and N; X.sup.3 and X.sup.5 may be the same or different and each is independently selected from C, N and O; Y is N; 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; R.sup.3 and R.sup.5 may be present or absent and may be the same or different and, when present, each is independently selected from H and C.sub.1-C.sub.6 alkyl, provided that the number of R.sup.3 groups present is such that the valency of X.sup.3 is maintained, and the number of R.sup.5 groups present is such that the valency of X.sup.5 is maintained; R.sup.21 is selected from H, C.sub.1-C.sub.6 alkyl, ##STR00043## wherein R.sup.211 is a group selected from: H; C.sub.1-C.sub.6 alkyl, unsubstituted or substituted with 1 to 3 substituents independently selected from —OH, C.sub.3-C.sub.6 cycloalkyl, —NH.sub.2, —NH—C.sub.1-C.sub.6 alkyl, —N(C.sub.1-C.sub.6 alkyl)(C.sub.1-C.sub.6 alkyl), —N(C.sub.1-C.sub.6 alkyl)(SO.sub.2—C.sub.1-C.sub.6 alkyl), —NH—SO.sub.2—C.sub.1-C.sub.6 alkyl, —C(O)OH, —C(O)O—C.sub.1-C.sub.6 alkyl, —C(O)—NH—C.sub.1-C.sub.6 alkyl, phenyl, tetrahydropyranyl, piperidinyl, pyrrolidinyl and pyridinyl; C.sub.3-C.sub.6 cycloalkyl; phenyl, unsubstituted or substituted with 1 to 3 substituents independently selected from C.sub.1-C.sub.6 alkyl, halogen and —SO.sub.2—C.sub.1-C.sub.6 alkyl; naphthyl; and a heterocyclic ring selected from the group consisting of tetrahydropyranyl, piperidinyl, pyrrolidinyl, and pyridinyl, each of which is unsubstituted or substituted with 1 to 3 substituents independently selected from C.sub.1-C.sub.6 alkyl, —C(O)—C.sub.1-C.sub.6 alkyl and —SO.sub.2—C.sub.1-C.sub.6 alkyl; R.sup.22 is selected from the group consisting of H and C.sub.1-C.sub.6 alkyl; and Cy is a cyclic organic group selected from phenyl and pyridinyl, wherein each of the phenyl and pyridinyl is unsubstituted or substituted with 1 to 3 substituents independently selected from C.sub.1-C.sub.6 alkyl, —CN, halogen, —OH, —NO.sub.2 and —O—C.sub.1-C.sub.6 alkyl.
2. (canceled)
3. The compound of claim 1 selected from the group consisting of: ##STR00044## ##STR00045## or a pharmaceutically acceptable salt thereof.
4. (canceled)
5. The compound of claim 1, wherein Cy is phenyl, unsubstituted or substituted with 1 to 3 substituents independently selected from C.sub.1-C.sub.6 alkyl, —CN, halogen, —OH, —NO.sub.2 and —O—C.sub.1-C.sub.6 alkyl: or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1, wherein, where present, R.sup.3 and R.sup.5 are each independently selected from H and a linear or branched C.sub.1-C.sub.6 alkyl group; or a pharmaceutically acceptable salt thereof.
7-8. (canceled)
9. The compound of claim 1, wherein R.sup.21 has one of the following structures: ##STR00046## wherein R.sup.211 is a group selected from: H; C.sub.1-C.sub.6 alkyl, unsubstituted or substituted with 1 to 3 substituents independently selected from —OH, C.sub.3-C.sub.6 cycloalkyl, —NH.sub.2, —NH—C.sub.1-C.sub.6 alkyl, —N(C.sub.1-C.sub.6 alkyl)(C.sub.1-C.sub.6 alkyl), —N(C.sub.1-C.sub.6 alkyl)(SO.sub.2—C.sub.1-C.sub.6 alkyl), —NH—SO.sub.2—C.sub.1-C.sub.6 alkyl, —C(O)OH, —C(O)O—C.sub.1-C.sub.6 alkyl, —C(O)—NH—C.sub.1-C.sub.6 alkyl, phenyl and tetrahydropyranyl; C.sub.3-C.sub.6 cycloalkyl; phenyl, unsubstituted or substituted with 1 to 3 substituents independently selected from C.sub.1-C.sub.6 alkyl, halogen and —SO.sub.2—C.sub.1-C.sub.6 alkyl; naphthyl; and a heterocyclic ring selected from the group consisting of tetrahydropyranyl, piperidinyl, pyrrolidinyl, and pyridinyl, each of which is unsubstituted or substituted with 1 to 3 substituents independently selected from C.sub.1-C.sub.6 alkyl, —C(O)—C.sub.1-C.sub.6 alkyl and —SO.sub.2—C.sub.1-C.sub.6 alkyl; or a pharmaceutically acceptable salt thereof.
10. (canceled)
11. The compound of claim 1 selected from the group consisting of: ##STR00047## ##STR00048## ##STR00049## ##STR00050## ##STR00051## ##STR00052## ##STR00053## ##STR00054## ##STR00055## ##STR00056## ##STR00057## ##STR00058## ##STR00059## or a pharmaceutically acceptable salt thereof.
12. (canceled)
13. A method for treating a disease or a disorder selected from: a cancer, an inflammatory condition, an infectious disease, a central nervous system disease or disorder, coronary heart disease, chronic renal failure, post anaesthesia cognitive dysfunction, a disease condition or disorder relating to female reproductive health, and cataracts, comprising administering to a patient a compound of claim 1, or a pharmaceutically acceptable salt thereof.
14. The method of claim 13, wherein the inflammatory condition is a condition relating to immune B cell, T cell, dendritic cell, natural killer cell, macrophage, and/or neutrophil dysregulation.
15. The method of claim 13, wherein the compound is an IDO inhibitor, or a pharmaceutically acceptable salt thereof, and the cancer is a cancer selected from: a solid or liquid tumour including cancer of the eye, brain (such as gliomas, glioblastomas, medullablastomas, craniopharyngioma, ependymoma, and astrocytoma), spinal cord, kidney, mouth, lip, throat, oral cavity, nasal cavity, small intestine, colon, parathyroid gland, gall bladder, head and neck, breast, bone, bile duct, cervix, heart, hypopharyngeal gland, lung, bronchus, liver, skin, ureter, urethra, testicles, vagina, anus, laryngeal gland, ovary, thyroid, oesophagus, nasopharyngeal gland, pituitary gland, salivary gland, prostate, pancreas, adrenal glands; an endometrial cancer, oral cancer, melanoma, neuroblastoma, gastric cancer, an angiomatosis, a hemangioblastoma, a pheochromocytoma, a pancreatic cyst, a renal cell carcinoma, Wilms' tumour, squamous cell carcinoma, sarcoma, osteosarcoma, Kaposi sarcoma, rhabdomyosarcoma, hepatocellular carcinoma, PTEN Hamartoma-Tumor Syndromes (PHTS) (such as Lhermitte-Duclos disease, Cowden syndrome, Proteus syndrome, and Proteus-like syndrome), leukaemias and lymphomas (such as acute lymphoblastic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia, chronic myelogenous leukaemia, hairy cell leukaemia, T-cell prolymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, adult T-cell leukemia, juvenile myelomonocytic leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, mantle lymphoma, follicular lymphoma, primary effusion lymphoma, AIDS-related lymphoma, Hodgkin lymphoma, diffuse B cell lymphoma, Burkitt lymphoma, and cutaneous T-cell lymphoma), preferably wherein the cancer is a cancer selected from acute myeloid leukemia (AML), a small-cell lung cancer, a melanoma, an ovarian cancer, a colorectal cancer, a pancreatic cancer, an endometrial cancer, and a skin papilloma.
16. The method of claim 13, wherein the compound is a TDO inhibitor, or a pharmaceutically acceptable salt thereof, and the cancer is a cancer selected from: a solid or liquid tumour including cancer of the eye, brain (such as gliomas, glioblastomas, medullablastomas, craniopharyngioma, ependymoma, and astrocytoma), spinal cord, kidney, mouth, lip, throat, oral cavity, nasal cavity, small intestine, colon, parathyroid gland, gall bladder, head and neck, breast, bone, bile duct, cervix, heart, hypopharyngeal gland, lung, bronchus, liver, skin, ureter, urethra, testicles, vagina, anus, laryngeal gland, ovary, thyroid, oesophagus, nasopharyngeal gland, pituitary gland, salivary gland, prostate, pancreas, adrenal glands; an endometrial cancer, oral cancer, melanoma, neuroblastoma, gastric cancer, an angiomatosis, a hemangioblastoma, a pheochromocytoma, a pancreatic cyst, a renal cell carcinoma, Wilms' tumour, squamous cell carcinoma, sarcoma, osteosarcoma, Kaposi sarcoma, rhabdomyosarcoma, hepatocellular carcinoma, PTEN Hamartoma-Tumor Syndromes (PHTS) (such as Lhermitte-Duclos disease, Cowden syndrome, Proteus syndrome, and Proteus-like syndrome), leukaemias and lymphomas (such as acute lymphoblastic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia, chronic myelogenous leukaemia, hairy cell leukaemia, T-cell prolymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, adult T-cell leukemia, juvenile myelomonocytic leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, mantle lymphoma, follicular lymphoma, primary effusion lymphoma, AIDS-related lymphoma, Hodgkin lymphoma, diffuse B cell lymphoma, Burkitt lymphoma, and cutaneous T-cell lymphoma) preferably wherein the cancer is a cancer selected from a glioma, and a hepatocellular carcinoma.
17. The method of claim 13, wherein the infectious disease is selected from a bacterial infection and a viral infection, preferably a gut infection, sepsis, and sepsis induced hypotension.
18. The method of claim 13, wherein the central nervous system disease or disorder is selected from amyotrophic lateral sclerosis (AML), Huntington's disease, Alzheimer's disease, pain, a psychiatric disorder, multiple sclerosis, Parkinson's disease, and HIV related neurocognitive decline.
19. The method of claim 13, wherein the disease or disorder relating to female reproductive health is endometriosis, or the condition relating to female reproductive health is contraception or abortion.
20. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
21-22. (canceled)
23. The pharmaceutical composition of claim 20 for treating a cancer, further comprising a further agent for treating cancer; wherein the further agent for treating cancer is selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormone analogues, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, immunotherapeutic agents (such as an anti-tumour vaccine, an oncolytic virus, an immune stimulatory antibody such as anti-CTLA4, anti-PD1, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR, a novel adjuvant, a peptide, a cytokine, a chimeric antigen receptor T cell therapy (CAR-T), a small molecule immune modulator, tumour microenvironment modulators, and anti-angiogenic agents), proapoptotic agents and cell cycle signalling inhibitors.
24. The pharmaceutical composition of claim 23, wherein the further agent is selected from: an anti-tumour vaccine; a cancer immunotherapy treatment (such as an immune checkpoint modulator such as an anti-CTLA4, anti-PD1, anti PDL-1, anti-LAG3, or anti-TIM3 agent, and CD40, OX40, 41BB or GITR agonists); an immunomodulator; an immunosuppressant; a cytokine therapy; a tyrosine kinase inhibitor; and a chimeric antigen receptor T cell therapy (CAR-T).
25. A pharmaceutical kit for treating a cancer, which pharmaceutical kit comprises: (a) a compound of claim 1, or a pharmaceutically acceptable salt thereof; and (b) a further agent for treating cancer; wherein the further agent for treating cancer is selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormone analogues, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, immunotherapeutic agents (such as an anti-tumour vaccine, an oncolytic virus, an immune stimulatory antibody such as anti-CTLA4, anti-PD1, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR, a novel adjuvant, a peptide, a cytokine, a chimeric antigen receptor T cell therapy (CAR-T), a small molecule immune modulator, tumour microenvironment modulators, and anti-angiogenic agents), proapoptotic agents and cell cycle signalling inhibitors; wherein the compound and the further agent are suitable for administration simultaneously, sequentially or separately.
26-29. (canceled)
30. The compound of claim 1 selected from the group consisting of: ##STR00060## ##STR00061## ##STR00062## ##STR00063## ##STR00064## ##STR00065## ##STR00066## ##STR00067## or a pharmaceutically acceptable salt thereof.
31. (canceled)
32. A method of synthesis of a compound of claim 30, or a pharmaceutically acceptable salt thereof, which method comprises a ring closing step to form the five-membered ring.
Description
[0124] The invention will now be explained in more detail, by way of example only, with reference to the following Figures.
[0125]
[0126]
[0127] The invention will now be described in more detail. Firstly a number of typical general structures of the compounds of the invention will be described.
[0128] As has been described, the invention relates to 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:
##STR00007##
[0129] wherein X.sup.1 is selected from C and N; X.sup.3 and X.sup.5 may 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; R.sup.3 and R.sup.5 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 R.sup.3 groups present is such that the valency of X.sup.3 is maintained, and the number of R.sup.5 groups present is such that the valency of X.sup.5 is maintained; each R.sup.11 and R.sup.12 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 R.sup.11 and R.sup.12 groups present is such that the valency of Z is maintained; R.sup.21 is selected from H and a substituted or unsubstituted organic group; R.sup.22 may be present or absent and is selected from H and a substituted or unsubstituted organic group; and Cy is a cyclic organic group.
[0130] As has been mentioned, this definition includes compounds in which, where one or two R groups are attached to the same atom, they may together form a group which is double bonded to that atom, such as a carbonyl group (═O) or an alkene group (═C(R′).sub.2) (wherein each R′ group is the same or different and is H or an organic group, preferably H or a straight or branched C.sub.1-C.sub.6 alkyl group). Accordingly, in some embodiments R.sup.3 or R.sup.5 may be a ═O group.
[0131] The ring Q has at least one unsaturated bond between two adjacent ring atoms, but may also have 2 unsaturated bonds, depending upon the bonding between the X atoms, the N atom and the C atom in the ring. The ring may be aromatic in some cases, but non-aromatic rings are not excluded. All tautomeric forms of ring Q are included.
[0132] In typical embodiments, one of X.sup.3 and X.sup.5 is not a C atom. In more typical embodiments, one or both of X.sup.3 and X.sup.5 is an N atom, i.e. X.sup.3 is N and/or X.sup.5 is N. In other typical embodiments, one of X.sup.3 and X.sup.5 is an O atom, i.e. X.sup.3 is O or X.sup.5 is O. When X.sup.3 is O, X.sup.5 may be C or N and when X.sup.5 is O, X.sup.3 may be C or N.
[0133] In typical embodiments both above and below herein, X.sup.1 is a C atom.
[0134] In typical embodiments both above and below herein, Z(R.sup.11)(R.sup.12) is absent.
[0135] In typical embodiments both above and below herein, Y is an N atom.
[0136] In typical embodiments both above and below herein, Cy is a 5- or 6- or 7-membered carbocyclic or heterocyclic ring, which is typically aromatic, although aliphatic rings are not excluded.
[0137] Thus, in view of the typical embodiments already described, in more typical embodiments the invention relates to a compound as defined above, which compound comprises one or other of the following formulae:
##STR00008## ##STR00009##
[0138] wherein, in each case, the substituents Cy, Q, R and X are as defined in any of the above embodiments.
[0139] Furthermore, in view of the typical embodiments already described, in more typical embodiments the invention relates to compound, which compound comprises the following formula:
##STR00010## ##STR00011##
[0140] Furthermore, in view of the typical embodiments already described, in more typical embodiments the invention relates to compound, which compound comprises the following formula:
##STR00012## ##STR00013## ##STR00014##
[0141] The Cy, R and X groups are in all of the compounds and structures herein will now be described in more detail.
[0142] As has been mentioned, the number of R substituents on an X or a ring atom will depend on its valency. Thus, it will be apparent in all of the embodiments of the invention, both above and below, that when X or a ring atom has three ring bonds (either 3 single bonds or a single bond and a double bond), it will have no substituents if it is N and 1 substituent (H or an organic group as defined herein) if it is C, and when X or a ring atom has two ring bonds (2 single bonds), it will have 1 substituent (H or an organic group as defined herein) if it is N and 2 substituents if it is C (each independently chosen from H or an organic group as defined herein). Of course, if X is O there will not be any substituents.
[0143] As has been mentioned, in all of the embodiments of this invention (both above and below herein), the substituent is not especially limited, provided that it does not prevent the TDO or IDO inhibitory function from occurring. However, in typical embodiments, the substituents may be selected independently as follows.
[0144] R.sup.3, and R.sup.5 are typically each independently selected from H and a group selected from the following groups: [0145] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0146] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0147] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, —CH.sub.2Cl, —CH.sub.2Br, —CH.sub.2I, —CF.sub.3, —CCl.sub.3—CBr.sub.3, —Cl.sub.3, —CH.sub.2CF.sub.3, —CH.sub.2CCl.sub.3, —CH.sub.2CBr.sub.3, and —CH.sub.2Cl.sub.3); [0148] —NH.sub.2 or a substituted or unsubstituted linear or branched primary secondary or tertiary C.sub.1-C.sub.6 amine group (such as —NMeH, —NMe.sub.2, —NEtH, —NEtMe, —NEt.sub.2, —NPrH, —NPrMe, —NPrEt, —NPr.sub.2, —NBuH, —NBuMe, —NBuEt, —CH.sub.2—NH.sub.2, —CH.sub.2—NMeH, —CH.sub.2—NMe.sub.2, —CH.sub.2—NEtH, —CH.sub.2—NEtMe, —CH.sub.2—NEt.sub.2, —CH.sub.2—NPrH, —CH.sub.2—NPrMe, and —CH.sub.2—NPrEt); [0149] a substituted or unsubstituted amino-aryl group (such as —NH-Ph, —NH-(2,3 or 4)F-Ph, —NH-(2,3 or 4)Cl-Ph, —NH-(2,3 or 4)Br-Ph, —NH-(2,3 or 4)I-Ph, —NH-(2,3 or 4)Me-Ph, —NH-(2,3 or 4)Et-Ph, —NH-(2,3 or 4)Pr-Ph, —NH-(2,3 or 4)Bu-Ph, NH-(2,3 or 4)OMe-Ph, —NH-(2,3 or 4)OEt-Ph, —NH-(2,3 or 4)OPr-Ph, —NH-(2,3 or 4)OBu-Ph, —NH-2,(3,4,5 or 6)F.sub.2-Ph, —NH-2,(3,4,5 or 6)Cl.sub.2-Ph, —NH-2,(3,4,5 or 6)Br.sub.2-Ph, —NH-2,(3,4,5 or 6)I.sub.2-Ph, —NH-2,(3,4,5 or 6)Me.sub.2-Ph, —NH-2,(3,4,5 or 6)Et.sub.2-Ph, —NH-2,(3,4,5, or 6)Pr.sub.2-Ph, —NH-2,(3,4,5 or 6)Bu.sub.2-Ph, [0150] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0151] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0152] an —OH group or a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alcohol group (such as —CH.sub.2OH, —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH); —a linear or branched C.sub.1-C.sub.6 carboxylic acid group (such as —COOH, —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0153] a substituted or unsubstituted linear or branched carbonyl group (such as —(CO)Me, —(CO)Et, —(CO)Pr, —(CO)iPr, —(CO)nBu, —(CO)iBu, —(CO)tBu, —(CO)Ph, —(CO)CH.sub.2Ph, —(CO)CH.sub.2OH, —(CO)CH.sub.2OCH.sub.3, —(CO)CH.sub.2NH.sub.2, —(CO)CH.sub.2NHMe, —(CO)CH.sub.2NMe.sub.2, —(CO)-cyclopropyl, —(CO)-1,3-epoxypropan-2-yl; —(CO)NH.sub.2, —(CO)NHMe, —(CO)NMe.sub.2, —(CO)NHEt, —(CO)NEt.sub.2, —(CO)-pyrollidine-N-yl, —(CO)-morpholine-N-yl, —(CO)-piperazine-N-yl, —(CO)—N-methyl-piperazine-N-yl, —(CO)NHCH.sub.2CH.sub.2OH, —(CO)NHCH.sub.2CH.sub.2OMe, —(CO)NHCH.sub.2CH.sub.2NH.sub.2, —(CO)NHCH.sub.2CH.sub.2NHMe, and —(CO)NHCH.sub.2CH.sub.2NMe.sub.2; [0154] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid ester group (such as —COOMe, —COOEt, —COOPr, —COO-i-Pr, —COO-n-Bu, —COO-i-Bu, —COO-t-Bu, —CH.sub.2COOMe, —CH.sub.2CH.sub.2COOMe, —CH.sub.2CH.sub.2CH.sub.2COOMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOMe); [0155] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 amide group (such as —CO—NH.sub.2, —CO—NMeH, —CO—NMe.sub.2, —CO—NEtH, —CO—NEtMe, —CO—NEt.sub.2, —CO—NPrH, —CO—NPrMe, and —CO—NPrEt); [0156] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 amino carbonyl group (such as —NH—CO-Me, —NH—CO-Et, —NH—CO—Pr, —NH—CO-Bu, —NH—CO-pentyl, —NH—CO-hexyl, —NH—CO-Ph, —NMe-CO-Me, —NMe-CO-Et, —NMe-CO—Pr, —NMe-CO-Bu, —NMe-CO-pentyl, —NMe-CO-hexyl, —NMe-CO-Ph; [0157] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 alkoxy or aryloxy group (such as —OMe, —OEt, —OPr, —O-i-Pr, —O-n-Bu, —O-i-Bu, —O-t-Bu, —O-pentyl, —O-hexyl, —OCH.sub.2F, —OCHF.sub.2, —OCF.sub.3, —OCH.sub.2Cl, —OCHCl.sub.2, —OCCl.sub.3, —O-Ph, —O—CH.sub.2-Ph, —O—CH.sub.2-(2,3 or 4)-F-Ph, —O—CH.sub.2-(2,3 or 4)-Cl-Ph, —CH.sub.2OMe, —CH.sub.2OEt, —CH.sub.2OPr, —CH.sub.2OBu, —CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe); [0158] a substituted or unsubstituted linear or branched aminoalkoxy group (such as —OCH.sub.2NH.sub.2, —OCH.sub.2NHMe, —OCH.sub.2NMe.sub.2, —OCH.sub.2NHEt, —OCH.sub.2NEt.sub.2, —OCH.sub.2CH.sub.2NH.sub.2, —OCH.sub.2CH.sub.2NHMe, —OCH.sub.2CH.sub.2NMe.sub.2, —OCH.sub.2CH.sub.2NHEt, and —OCH.sub.2CH.sub.2NEt.sub.2; [0159] a substituted or unsubstituted sulphonyl group (such as —SO.sub.2Me, —SO.sub.2Et, —SO.sub.2Pr, —SO.sub.2iPr, —SO.sub.2Ph, —SO.sub.2-(2,3 or 4)-F-Ph, —SO.sub.2-cyclopropyl, —SO.sub.2CH.sub.2CH.sub.2OCH.sub.3), —SO.sub.2NH.sub.2, —SO.sub.2NHMe, —SO.sub.2NMe.sub.2, —SO.sub.2NHEt, —SO.sub.2NEt.sub.2, —SO.sub.2-pyrrolidine-N-yl, —SO.sub.2-morpholine-N-yl, —SO.sub.2NHCH.sub.2OMe, and —SO.sub.2NHCH.sub.2CH.sub.2OMe; [0160] a substituted or unsubstituted aminosulphonyl group (such as —NHSO.sub.2Me, —NHSO.sub.2Et, —NHSO.sub.2Pr, —NHSO.sub.2iPr, —NHSO.sub.2Ph, —NHSO.sub.2-(2,3 or 4)-F-Ph, —NHSO.sub.2-cyclopropyl, —NHSO.sub.2CH.sub.2CH.sub.2OCH.sub.3); [0161] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); [0162] a saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-1-yl, pyrrole-2-yl, pyrrole-3-yl, pyrazole-1-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-1-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-1-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-1-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-1-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-1-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-1-yl, tetrazole-2-yl, tetrazole-5-yl); and [0163] where there are one or two R groups attached to the same atom, they may together form a group which is double bonded to that atom, (such as a carbonyl group (═O) or an alkene group (═C(R′).sub.2) (wherein each R′ group is the same or different and is H or an organic group, preferably H or a straight or branched C.sub.1-C.sub.6 alkyl group)).
[0164] More typically R.sup.5 is independently selected from H and a group selected from the following groups: [0165] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0166] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2C.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0167] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, —CH.sub.2Cl, —CH.sub.2Br, —CH.sub.2I, —CF.sub.3, —CCl.sub.3—CBr.sub.3, —Cl.sub.3, —CH.sub.2CF.sub.3, —CH.sub.2CCl.sub.3, —CH.sub.2CBr.sub.3, and —CH.sub.2Cl.sub.3); [0168] —NH.sub.2 or a substituted or unsubstituted linear or branched primary secondary or tertiary C.sub.1-C.sub.6 amine group (such as —NMeH, —NMe.sub.2, —NEtH, —NEtMe, —NEt.sub.2, —NPrH, —NPrMe, —NPrEt, —NPr.sub.2, —NBuH, —NBuMe, —NBuEt, —CH.sub.2—NH.sub.2, —CH.sub.2—NMeH, —CH.sub.2—NMe.sub.2, —CH.sub.2—NEtH, —CH.sub.2—NEtMe, —CH.sub.2—NEt.sub.2, —CH.sub.2—NPrH, —CH.sub.2—NPrMe, and —CH.sub.2—NPrEt); [0169] a substituted or unsubstituted amino-aryl group (such as —NH-Ph, —NH-(2,3 or 4)F-Ph, —NH-(2,3 or 4)Cl-Ph, —NH-(2,3 or 4)Br-Ph, —NH-(2,3 or 4)I-Ph, —NH-(2,3 or 4)Me-Ph, —NH-(2,3 or 4)Et-Ph, —NH-(2,3 or 4)Pr-Ph, —NH-(2,3 or 4)Bu-Ph, NH-(2,3 or 4)OMe-Ph, —NH-(2,3 or 4)OEt-Ph, —NH-(2,3 or 4)OPr-Ph, —NH-(2,3 or 4)OBu-Ph, —NH-2,(3,4,5 or 6)F.sub.2-Ph, —NH-2,(3,4,5 or 6)Cl.sub.2-Ph, —NH-2,(3,4,5 or 6)Br.sub.2-Ph, —NH-2,(3,4,5 or 6)I.sub.2-Ph, —NH-2,(3,4,5 or 6)Me.sub.2-Ph, —NH-2,(3,4,5 or 6)Et.sub.2-Ph, —NH-2,(3,4,5, or 6)Pr.sub.2-Ph, —NH-2,(3,4,5 or 6)Bu.sub.2-Ph, [0170] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0171] a cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0172] an —OH group or a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alcohol group (such as —CH.sub.2OH, —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH); —a linear or branched C.sub.1-C.sub.6 carboxylic acid group (such as —COOH, —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0173] a substituted or unsubstituted linear or branched carbonyl group (such as —(CO)Me, —(CO)Et, —(CO)Pr, —(CO)iPr, —(CO)nBu, —(CO)iBu, —(CO)tBu, —(CO)Ph, —(CO)CH.sub.2Ph, —(CO)CH.sub.2OH, —(CO)CH.sub.2OCH.sub.3, —(CO)CH.sub.2NH.sub.2, —(CO)CH.sub.2NHMe, —(CO)CH.sub.2NMe.sub.2, —(CO)-cyclopropyl, —(CO)-1,3-epoxypropan-2-yl; —(CO)NH.sub.2, —(CO)NHMe, —(CO)NMe.sub.2, —(CO)NHEt, —(CO)NEt.sub.2, —(CO)-pyrollidine-N-yl, —(CO)-morpholine-N-yl, —(CO)-piperazine-N-yl, —(CO)—N-methyl-piperazine-N-yl, —(CO)NHCH.sub.2CH.sub.2OH, —(CO)NHCH.sub.2CH.sub.2OMe, —(CO)NHCH.sub.2CH.sub.2NH.sub.2, —(CO)NHCH.sub.2CH.sub.2NHMe, and —(CO)NHCH.sub.2CH.sub.2NMe.sub.2; [0174] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid ester group (such as —COOMe, —COOEt, —COOPr, —COO-i-Pr, —COO-n-Bu, —COO-i-Bu, —COO-t-Bu, —CH.sub.2COOMe, —CH.sub.2CH.sub.2COOMe, —CH.sub.2CH.sub.2CH.sub.2COOMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOMe); [0175] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 amide group (such as —CO—NH.sub.2, —CO—NMeH, —CO—NMe.sub.2, —CO—NEtH, —CO—NEtMe, —CO—NEt.sub.2, —CO—NPrH, —CO—NPrMe, and —CO—NPrEt); [0176] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 amino carbonyl group (such as —NH—CO-Me, —NH—CO-Et, —NH—CO—Pr, —NH—CO-Bu, —NH—CO-pentyl, —NH—CO-hexyl, —NH—CO-Ph, —NMe-CO-Me, —NMe-CO-Et, —NMe-CO—Pr, —NMe-CO-Bu, —NMe-CO-pentyl, —NMe-CO-hexyl, —NMe-CO-Ph; [0177] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 alkoxy or aryloxy group (such as —OMe, —OEt, —OPr, —O-i-Pr, —O-n-Bu, —O-i-Bu, —O-t-Bu, —O-pentyl, —O-hexyl, —OCH.sub.2F, —OCHF.sub.2, —OCF.sub.3, —OCH.sub.2Cl, —OCHCl.sub.2, —OCCl.sub.3, —O-Ph, —O—CH.sub.2-Ph, —O—CH.sub.2-(2,3 or 4)-F-Ph, —O—CH.sub.2-(2,3 or 4)-Cl-Ph, —CH.sub.2OMe, —CH.sub.2OEt, —CH.sub.2OPr, —CH.sub.2OBu, —CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe); [0178] a substituted or unsubstituted linear or branched aminoalkoxy group (such as —OCH.sub.2NH.sub.2, —OCH.sub.2NHMe, —OCH.sub.2NMe.sub.2, —OCH.sub.2NHEt, —OCH.sub.2NEt.sub.2, —OCH.sub.2CH.sub.2NH.sub.2, —OCH.sub.2C H.sub.2NHMe, —OCH.sub.2CH.sub.2NMe.sub.2, —OCH.sub.2CH.sub.2NHEt, and —OCH.sub.2CH.sub.2NEt.sub.2; [0179] a substituted or unsubstituted sulphonyl group (such as —SO.sub.2Me, —SO.sub.2Et, —SO.sub.2Pr, —SO.sub.2iPr, —SO.sub.2Ph, —SO.sub.2-(2,3 or 4)-F-Ph, —SO.sub.2— cyclopropyl, —SO.sub.2CH.sub.2CH.sub.2OCH.sub.3), —SO.sub.2NH.sub.2, —SO.sub.2NHMe, —SO.sub.2NMe.sub.2, —SO.sub.2NHEt, —SO.sub.2NEt.sub.2, —SO.sub.2-pyrrolidine-N-yl, —SO.sub.2-morpholine-N-yl, —SO.sub.2NHCH.sub.2OMe, and —SO.sub.2NHCH.sub.2CH.sub.2OMe; [0180] a substituted or unsubstituted aminosulphonyl group (such as —NHSO.sub.2Me, —NHSO.sub.2Et, —NHSO.sub.2Pr, —NHSO.sub.2iPr, —NHSO.sub.2Ph, —NHSO.sub.2-(2,3 or 4)-F-Ph, —NHSO.sub.2-cyclopropyl, —NHSO.sub.2CH.sub.2CH.sub.2OCH.sub.3); [0181] a saturated or unsaturated, substituted or unsubstituted, non-aromatic heterocyclic group (such as pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-1-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-1-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-1-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, and thiane-4-yl); and [0182] where there are one or two R groups attached to the same atom, they may together form a group which is double bonded to that atom, (such as a carbonyl group (═O) or an alkene group (═C(R′).sub.2) (wherein each R′ group is the same or different and is H or an organic group, preferably H or a straight or branched C.sub.1-C.sub.6 alkyl group)).
[0183] More typically, R.sup.3 and R.sup.5 may each be selected independently from: H, a substituted or unsubstituted C.sub.1-C.sub.6 alkyl group, an —NH.sub.2 group or a substituted or unsubstituted C.sub.1-C.sub.6 amino group, a substituted or unsubstituted C.sub.1-C.sub.6 alkoxy group, and a nitrile group.
[0184] R.sup.100, R.sup.101, R.sup.102, R.sup.103 R.sup.104, R.sup.115, R.sup.11, and R.sup.12, are each independently selected from H and a group selected from the following groups: [0185] a halogen (such as —F, —Cl, —Br and —I); [0186] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0187] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0188] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, —CH.sub.2Cl, —CH.sub.2Br, —CH.sub.2I, —CF.sub.3, —CCl.sub.3—CBr.sub.3, —CI.sub.3, —CH.sub.2CF.sub.3, —CH.sub.2CCl.sub.3, —CH.sub.2CBr.sub.3, and —CH.sub.2CI.sub.3); [0189] —NH.sub.2 or a substituted or unsubstituted linear or branched primary secondary or tertiary C.sub.1-C.sub.6 amine group (such as —NMeH, —NMe.sub.2, —NEtH, —NEtMe, —NEt.sub.2, —NPrH, —NPrMe, —NPrEt, —NPr.sub.2, —NBuH, —NBuMe, —NBuEt, —CH.sub.2—NH.sub.2, —CH.sub.2—NMeH, —CH.sub.2—NMe.sub.2, —CH.sub.2—NEtH, —CH.sub.2—NEtMe, —CH.sub.2—NEt.sub.2, —CH.sub.2—NPrH, —CH.sub.2—NPrMe, and —CH.sub.2—NPrEt); [0190] a substituted or unsubstituted amino-aryl group (such as —NH-Ph, —NH-(2,3 or 4)F-Ph, —NH-(2,3 or 4)Cl-Ph, —NH-(2,3 or 4)Br-Ph, —NH-(2,3 or 4)I-Ph, —NH-(2,3 or 4)Me-Ph, —NH-(2,3 or 4)Et-Ph, —NH-(2,3 or 4)Pr-Ph, —NH-(2,3 or 4)Bu-Ph, NH-(2,3 or 4)OMe-Ph, —NH-(2,3 or 4)OEt-Ph, —NH-(2,3 or 4)OPr-Ph, —NH-(2,3 or 4)OBu-Ph, —NH-2,(3,4,5 or 6)F.sub.2-Ph, —NH-2,(3,4,5 or 6)Cl.sub.2-Ph, —NH-2,(3,4,5 or 6)Br.sub.2-Ph, —NH-2,(3,4,5 or 6)I.sub.2-Ph, —NH-2,(3,4,5 or 6)Me.sub.2-Ph, —NH-2,(3,4,5 or 6)Et.sub.2-Ph, —NH-2,(3,4,5, or 6)Pr.sub.2-Ph, —NH-2,(3,4,5 or 6)Bu.sub.2-Ph, [0191] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0192] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0193] an —OH group or a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alcohol group (such as —CH.sub.2OH, —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and -2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OCH H); —a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid group (such as —COOH, —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0194] a substituted or unsubstituted linear or branched carbonyl group (such as —(CO)Me, —(CO)Et, —(CO)Pr, —(CO)iPr, —(CO)nBu, —(CO)iBu, —(CO)tBu, —(CO)Ph, —(CO)CH.sub.2Ph, —(CO)CH.sub.2OH, —(CO)CH.sub.2OCH.sub.3, —(CO)CH.sub.2NH.sub.2, —(CO)CH.sub.2NHMe, —(CO)CH.sub.2NMe.sub.2, —(CO)-cyclopropyl, —(CO)-1,3-epoxypropan-2-yl; —(CO)NH.sub.2, —(CO)NHMe, —(CO)NMe.sub.2, —(CO)NHEt, —(CO)NEt.sub.2, —(CO)-pyrollidine-N-yl, —(CO)-morpholine-N-yl, —(CO)-piperazine-N-yl, —(CO)—N-methyl-piperazine-N-yl, —(CO)NHCH.sub.2CH.sub.2OH, —(CO)NHCH.sub.2CH.sub.2OMe, —(CO)NHCH.sub.2CH.sub.2NH.sub.2, —(CO)NHCH.sub.2CH.sub.2NHMe, and —(CO)NHCH.sub.2CH.sub.2NMe.sub.2; [0195] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid ester group (such as —COOMe, —COOEt, —COOPr, —COO-i-Pr, —COO-n-Bu, —COO-i-Bu, —COO-t-Bu, —CH.sub.2COOMe, —CH.sub.2CH.sub.2COOMe, —CH.sub.2CH.sub.2CH.sub.2COOMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOMe); [0196] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 amide group (such as —CO—NH.sub.2, —CO—NMeH, —CO—NMe.sub.2, —CO—NEtH, —CO—NEtMe, —CO—NEt.sub.2, —CO—NPrH, —CO—NPrMe, and —CO—NPrEt); [0197] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 amino carbonyl group (such as —NH—CO-Me, —NH—CO-Et, —NH—CO—Pr, —NH—CO-Bu, —NH—CO-pentyl, —NH—CO-hexyl, —NH—CO-Ph, —NMe-CO-Me, —NMe-CO-Et, —NMe-CO—Pr, —NMe-CO-Bu, —NMe-CO-pentyl, —NMe-CO-hexyl, —NMe-CO-Ph; [0198] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 alkoxy or aryloxy group (such as —OMe, —OEt, —OPr, —O-i-Pr, —O-n-Bu, —O-i-Bu, —O-t-Bu, —O-pentyl, —O-hexyl, —OCH.sub.2F, —OCHF.sub.2, —OCF.sub.3, —OCH.sub.2Cl, —OCHCl.sub.2, —OCCl.sub.3, —O-Ph, —O—CH.sub.2-Ph, —O—CH.sub.2-(2,3 or 4)-F-Ph, —O—CH.sub.2-(2,3 or 4)-Cl-Ph, —CH.sub.2OMe, —CH.sub.2OEt, —CH.sub.2OPr, —CH.sub.2OBu, —CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe); [0199] a substituted or unsubstituted linear or branched aminoalkoxy group (such as —OCH.sub.2NH.sub.2, —OCH.sub.2NHMe, —OCH.sub.2NMe.sub.2, —OCH.sub.2NHEt, —OCH.sub.2NEt.sub.2, —OCH.sub.2CH.sub.2NH.sub.2, —OCH.sub.2C H.sub.2NHMe, —OCH.sub.2CH.sub.2NMe.sub.2, —OCH.sub.2CH.sub.2NHEt, and —OCH.sub.2CH.sub.2NEt.sub.2; [0200] a substituted or unsubstituted sulphonyl group (such as —SO.sub.2Me, —SO.sub.2Et, —SO.sub.2Pr, —SO.sub.2iPr, —SO.sub.2Ph, —SO.sub.2-(2,3 or 4)-F-Ph, —SO.sub.2-cyclopropyl, —SO.sub.2CH.sub.2CH.sub.2OCH.sub.3), —SO.sub.2NH.sub.2, —SO.sub.2NHMe, —SO.sub.2NMe.sub.2, —SO.sub.2NHEt, —SO.sub.2NEt.sub.2, —SO.sub.2-pyrrolidine-N-yl, —SO.sub.2-morpholine-N-yl, —SO.sub.2NHCH.sub.2OMe, and —SO.sub.2NHCH.sub.2CH.sub.2OMe; [0201] a substituted or unsubstituted aminosulphonyl group (such as —NHSO.sub.2Me, —NHSO.sub.2Et, —NHSO.sub.2Pr, —NHSO.sub.2iPr, —NHSO.sub.2Ph, —NHSO.sub.2-(2,3 or 4)-F-Ph, —NHSO.sub.2-cyclopropyl, —NHSO.sub.2CH.sub.2CH.sub.2OCH.sub.3); [0202] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); [0203] a saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-1-yl, pyrrole-2-yl, pyrrole-3-yl, pyrazole-1-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-1-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-1-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-1-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-1-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-1-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-1-yl, tetrazole-2-yl, tetrazole-5-yl); and [0204] where there are two R groups attached to the same atom, they may together form a group which is double bonded to that atom, (such as a carbonyl group (═O) or an alkene group (═C(R′).sub.2) wherein each R′ group is the same or different and is H or an organic group, preferably H or a straight or branched C.sub.1-C.sub.6 alkyl group).
[0205] More typically, R.sup.100, R.sup.101, R.sup.102, R.sup.103 R.sup.104, R.sup.115, R.sup.11, and R.sup.12, are each independently selected from H, a halogen (such as —F, —Cl, —Br, and —I), a substituted or unsubstituted C.sub.1-C.sub.6 alkyl group, an —NH.sub.2 group or a substituted or unsubstituted C.sub.1-C.sub.6 amino group, a substituted or unsubstituted C.sub.1-C.sub.6 alkoxy group, and a nitrile group.
[0206] R.sup.21 and R.sup.22 are each independently selected from H and a group selected from the following groups: [0207] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0208] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0209] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, and —CH.sub.2CF.sub.3); [0210] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0211] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0212] a substituted or unsubstituted linear or branched C.sub.2-C.sub.6 alcohol group (such as —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH); [0213] a substituted or unsubstituted linear or branched C.sub.2-C.sub.6 carboxylic acid group (such as —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0214] a substituted or unsubstituted linear or branched carbonyl group (such as —(CO)Me, —(CO)Et, —(CO)Pr, —(CO)-i_Pr, —(CO)-n-Bu, —(CO)-i-Bu, —(CO)-t-Bu, —(CO)Ph, —(CO)CH.sub.2Ph, —(CO)CH.sub.2OH, —(CO)CH.sub.2OCH.sub.3, —(CO)CH.sub.2NH.sub.2, —(CO)CH.sub.2NHMe, —(CO)CH.sub.2NMe.sub.2, —(CO)-cyclopropyl, —(CO)—1,3-epoxypropan-2-yl; —(CO)NH.sub.2, —(CO)NHMe, —(CO)NMe.sub.2, —(CO)NHEt, —(CO)NEt.sub.2, —(CO)-pyrollidine-N-yl, —(CO)-morpholine-N-yl, —(CO)-piperazine-N-yl, —(CO)—N-methyl-piperazine-N-yl, —(CO)NHCH.sub.2CH.sub.2OH, —(CO)NHCH.sub.2CH.sub.2OMe, —(CO)NHCH.sub.2CH.sub.2NH.sub.2, —(CO)NHCH.sub.2CH.sub.2NHMe, and —(CO)NHCH.sub.2CH.sub.2NMe.sub.2; [0215] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid ester group (such as —COOMe, —COOEt, —COOPr, —COO-i-Pr, —COO-n-Bu, —COO-i-Bu, —COO-t-Bu, —CH.sub.2COOMe, —CH.sub.2CH.sub.2COOMe, —CH.sub.2CH.sub.2CH.sub.2COOMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOMe); [0216] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 amide group (such as —CO—NH.sub.2, —CO—NMeH, —CO—NMe.sub.2, —CO—NEtH, —CO—NEtMe, —CO—NEt.sub.2, —CO—NPrH, —CO—NPrMe, and —CO—NPrEt); [0217] a substituted or unsubstituted sulphonyl group (such as —SO.sub.2Me, —SO.sub.2Et, —SO.sub.2Pr, —SO.sub.2iPr, —SO.sub.2Ph, —SO.sub.2-(2,3 or 4)-F-Ph, —SO.sub.2-cyclopropyl, —SO.sub.2CH.sub.2CH.sub.2OCH.sub.3), —SO.sub.2NH.sub.2, —SO.sub.2NHMe, —SO.sub.2NMe.sub.2, —SO.sub.2NHEt, —SO.sub.2NEt.sub.2, —SO.sub.2-pyrrolidine-N-yl, —SO.sub.2-morpholine-N-yl, —SO.sub.2NHCH.sub.2OMe, and —SO.sub.2NHCH.sub.2CH.sub.2OMe; [0218] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); and [0219] a substituted or unsubstituted saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-2-yl, pyrrole-3-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-5-yl).
[0220] In some embodiments of the invention (both above and in the following), R.sup.21 typically comprises a group having one of the following structures:
##STR00015##
wherein R.sup.211 is a group selected from H and: [0221] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0222] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0223] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, —CH.sub.2Cl, —CH.sub.2Br, —CH.sub.2I, —CF.sub.3, —CCl.sub.3—CBr.sub.3, —Cl.sub.3, —CH.sub.2CF.sub.3, —CH.sub.2CCl.sub.3, —CH.sub.2CBr.sub.3, and —CH.sub.2Cl.sub.3); [0224] —NH.sub.2 or a substituted or unsubstituted linear or branched primary secondary or tertiary C.sub.1-C.sub.6 amine group (such as —NMeH, —NMe.sub.2, —NEtH, —NEtMe, —NEt.sub.2, —NPrH, —NPrMe, —NPrEt, —NPr.sub.2, —NBuH, —NBuMe, —NBuEt, —CH.sub.2—NH.sub.2, —CH.sub.2—NMeH, —CH.sub.2—NMe.sub.2, —CH.sub.2—NEtH, —CH.sub.2—NEtMe, —CH.sub.2—NEt.sub.2, —CH.sub.2—NPrH, —CH.sub.2—NPrMe, and —CH.sub.2—NPrEt); [0225] a substituted or unsubstituted amino-aryl group (such as —NH-Ph, —NH-(2,3 or 4)F-Ph, —NH-(2,3 or 4)Cl-Ph, —NH-(2,3 or 4)Br-Ph, —NH-(2,3 or 4)I-Ph, —NH-(2,3 or 4)Me-Ph, —NH-(2,3 or 4)Et-Ph, —NH-(2,3 or 4)Pr-Ph, —NH-(2,3 or 4)Bu-Ph, NH-(2,3 or 4)OMe-Ph, —NH-(2,3 or 4)OEt-Ph, —NH-(2,3 or 4)OPr-Ph, —NH-(2,3 or 4)OBu-Ph, —NH-2,(3,4,5 or 6)F.sub.2-Ph, —NH-2,(3,4,5 or 6)Cl.sub.2-Ph, —NH-2,(3,4,5 or 6)Br.sub.2-Ph, —NH-2,(3,4,5 or 6)I.sub.2-Ph, —NH-2,(3,4,5 or 6)Me.sub.2-Ph, —NH-2,(3,4,5 or 6)Et.sub.2-Ph, —NH-2,(3,4,5, or 6)Pr.sub.2-Ph, —NH-2,(3,4,5 or 6)Bu.sub.2-Ph, [0226] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0227] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0228] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alcohol group (such as —CH.sub.2OH, —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH); [0229] a substituted or unsubstituted linear or branched C.sub.2-C.sub.6 carboxylic acid group (such as —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0230] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 amino carbonyl group (such as —NH—CO-Me, —NH—CO-Et, —NH—CO—Pr, —NH—CO-Bu, —NH—CO-pentyl, —NH—CO-hexyl, —NH—CO-Ph, —NMe-CO-Me, —NMe-CO-Et, —NMe-CO—Pr, —NMe-CO-Bu, —NMe-CO-pentyl, —NMe-CO-hexyl, —NMe-CO-Ph; [0231] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 alkoxy or aryloxy group (such as —OMe, —OEt, —OPr, —O-i-Pr, —O-n-Bu, —O-i-Bu, —O-t-Bu, —O-pentyl, —O-hexyl, —OCH.sub.2F, —OCHF.sub.2, —OCF.sub.3, —OCH.sub.2Cl, —OCHCl.sub.2, —OCCl.sub.3, —O-Ph, —O—CH.sub.2-Ph, —O—CH.sub.2-(2,3 or 4)-F-Ph, —O—CH.sub.2-(2,3 or 4)-Cl-Ph, —CH.sub.2OMe, —CH.sub.2OEt, —CH.sub.2OPr, —CH.sub.2OBu, —CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe); [0232] a substituted or unsubstituted linear or branched aminoalkoxy group (such as —OCH.sub.2NH.sub.2, —OCH.sub.2NHMe, —OCH.sub.2NMe.sub.2, —OCH.sub.2NHEt, —OCH.sub.2NEt.sub.2, —OCH.sub.2CH.sub.2NH.sub.2, —OCH.sub.2C H.sub.2NHMe, —OCH.sub.2CH.sub.2NMe.sub.2, —OCH.sub.2CH.sub.2NHEt, and —OCH.sub.2CH.sub.2NEt.sub.2; [0233] an aminosulphonyl group (such as —NHSO.sub.2Me, —NHSO.sub.2Et, —NHSO.sub.2Pr, —NHSO.sub.2iPr, —NHSO.sub.2Ph, —NHSO.sub.2-(2,3 or 4)-F-Ph, —NHSO.sub.2-cyclopropyl, —NHSO.sub.2CH.sub.2CH.sub.2OCH.sub.3); [0234] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); and [0235] a saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-1-yl, pyrrole-2-yl, pyrrole-3-yl, pyrazole-1-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-1-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-1-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-1-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-1-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-1-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-1-yl, tetrazole-2-yl, tetrazole-5-yl).
[0236] In other embodiments of the invention (both above and in the following), R.sup.21 and R.sup.22 typically comprise a group selected from H and the following: [0237] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0238] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0239] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, and —CH.sub.2CF.sub.3; [0240] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0241] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0242] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); and [0243] a substituted or unsubstituted saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-2-yl, pyrrole-3-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-5-yl).
[0244] The Cy group may comprise a monocyclic group or a cyclic group comprising two or more fused or joined rings. It may be a heterocyclic ring or a carbocyclic ring. The ring may be fully saturated, or may be unsaturated such that it contains one or more double bonds. The ring may be aliphatic or aromatic. The ring may comprise any number of atoms provided that that it does not prevent the TDO or IDO inhibitory function from occurring. Typically the ring comprises from 3-10 atoms, 3-9 atoms, 3-8 atoms, 4-9 atoms, 5-8 atoms, 5-7 atoms or 5 or 6 or 7 atoms.
[0245] Thus, in certain embodiments, Cy may be a group of the following formula:
##STR00016##
[0246] wherein X.sup.10 is selected from C and N, and X.sup.11, X.sup.12, X.sup.13, X.sup.14 and X.sup.15 are independently selected from C, N, O and S (typically wherein X.sup.10 is C); each bond represented by a dotted line may independently be a double bond or a single bond, provided that valencies at each ring atom X.sup.10, X.sup.11, X.sup.12, X.sup.13, X.sup.14 and X.sup.15 are maintained; R.sup.100, R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 may be present or absent and when present are selected independently from H and an organic group, provided that the number of R.sup.110, R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 groups present is such that the valency of X.sup.10, X.sup.11, X.sup.12, X.sup.13, X.sup.14 and X.sup.15 is maintained.
[0247] In typical embodiments, where present, R.sup.100, R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 are selected from H, halogen (such as —F, —Cl, —Br, —I), substituted or unsubstituted C.sub.1-C.sub.6 alkyl, —NH.sub.2 or substituted or unsubstituted C.sub.1-C.sub.6 amino, substituted or unsubstituted C.sub.1-C.sub.6 alkoxy, and nitrile. Typically, where present, at least one of R.sup.100, R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 is not H, or all of R.sup.100, R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 are H). Thus in typical embodiments, Cy may be a 5-, 6-, or 7-membered ring, most typically a 6-membered ring, and typically an aromatic ring.
[0248] In further typical embodiments Cy comprises a group of the following formula:
##STR00017##
[0249] wherein X.sup.11, X.sup.12, X.sup.13, X.sup.14 and X.sup.15 are any of the substituents as defined above or below herein (in certain cases where all of X.sup.11, X.sup.12, X.sup.13, X.sup.14 and X.sup.15 are C or at least one of X.sup.11, X.sup.12, X.sup.13, X.sup.14 and X.sup.15 is N), and R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 may be present or absent and may be any of the substituents as defined above or below herein; preferably wherein, where present, R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 are selected from H, halogen (such as —F, —Cl, —Br, —I), substituted or unsubstituted C.sub.1-C.sub.6 alkyl, —NH.sub.2 or substituted or unsubstituted C.sub.1-C.sub.6 amino, substituted or unsubstituted C.sub.1-C.sub.6 alkoxy, and nitrile. Typically, where present, at least one of R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 is not H (typically N), or all of R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 are H).
[0250] Thus, Cy may be selected from the following: [0251] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0252] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0253] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); and [0254] a saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-1-yl, pyrrole-2-yl, pyrrole-3-yl, pyrazole-1-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-1-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-1-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-1-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-1-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-1-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-1-yl, tetrazole-2-yl, tetrazole-5-yl).
[0255] In some preferred embodiments, the invention therefore provides 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:
##STR00018##
[0256] wherein X.sup.1 is selected from C and N; X.sup.3 and X.sup.5 may 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 Q 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; R.sup.3 and R.sup.5 may be present or absent and may be the same or different, provided that the number of R.sup.3 groups present is such that the valency of X.sup.3 is maintained, and the number of R.sup.5 groups present is such that the valency of X.sup.5 is maintained; each R.sup.11 and R.sup.12 may be present or absent and may be the same or different, provided that the number of R.sup.11 and R.sup.12 groups present is such that the valency of Z is maintained; and R.sup.22 may be present or absent provided that the valency of Y is maintained;
[0257] and wherein Cy, —YR.sup.21R.sup.22, R.sup.3 and R.sup.5 do not comprise a substituted or unsubstituted indole or indazole group, and preferably wherein Cy, —YR.sup.21R.sup.22, R.sup.3 and R.sup.5 do not comprise a bicyclic group;
[0258] and wherein R.sup.3 and R.sup.5 do not comprise a group comprising an atom double-bonded to an oxygen atom at an α-, β-, or γ-position to the Q ring atom to which the R.sup.3 or R.sup.5 is attached and in which the atom double-bonded to an oxygen atom is also bonded to a hetero-atom;
[0259] and wherein Cy comprises a group of the following formula:
##STR00019##
[0260] wherein X.sup.10 is selected from C and N, and X.sup.11, X.sup.12, X.sup.13, X.sup.14 and X.sup.15 are independently selected from C, N, O and S, preferably wherein X.sup.10 is C, and R.sup.100, R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 may be present or absent provided that the number of R.sup.100, R.sup.101, R.sup.102, R.sup.103, R.sup.104 and R.sup.105 groups present is such that the valency of X.sup.10, X.sup.11, X.sup.12, X.sup.13, X.sup.14 and X.sup.15 is maintained;
[0261] and wherein R.sup.100, R.sup.101, R.sup.102, R.sup.103 R.sup.104, R.sup.105, R.sup.11, and R.sup.12, are each independently selected from H and a group selected from the following groups: [0262] a halogen (such as —F, —Cl, —Br and —I); [0263] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0264] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0265] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, —CH.sub.2Cl, —CH.sub.2Br, —CH.sub.2I, —CF.sub.3, —CCl.sub.3—CBr.sub.3, —Cl.sub.3, —CH.sub.2CF.sub.3, —CH.sub.2CCl.sub.3, —CH.sub.2CBr.sub.3, and —CH.sub.2Cl.sub.3); [0266] —NH.sub.2 or a substituted or unsubstituted linear or branched primary secondary or tertiary C.sub.1-C.sub.6 amine group (such as —NMeH, —NMe.sub.2, —NEtH, —NEtMe, —NEt.sub.2, —NPrH, —NPrMe, —NPrEt, —NPr.sub.2, —NBuH, —NBuMe, —NBuEt, —CH.sub.2—NH.sub.2, —CH.sub.2—NMeH, —CH.sub.2—NMe.sub.2, —CH.sub.2—NEtH, —CH.sub.2—NEtMe, —CH.sub.2—NEt.sub.2, —CH.sub.2—NPrH, —CH.sub.2—NPrMe, and —CH.sub.2—NPrEt); [0267] a substituted or unsubstituted amino-aryl group (such as —NH-Ph, —NH-(2,3 or 4)F-Ph, —NH-(2,3 or 4)Cl-Ph, —NH-(2,3 or 4)Br-Ph, —NH-(2,3 or 4)I-Ph, —NH-(2,3 or 4)Me-Ph, —NH-(2,3 or 4)Et-Ph, —NH-(2,3 or 4)Pr-Ph, —NH-(2,3 or 4)Bu-Ph, NH-(2,3 or 4)OMe-Ph, —NH-(2,3 or 4)OEt-Ph, —NH-(2,3 or 4)OPr-Ph, —NH-(2,3 or 4)OBu-Ph, —NH-2,(3,4,5 or 6)F.sub.2-Ph, —NH-2,(3,4,5 or 6)Cl.sub.2-Ph, —NH-2,(3,4,5 or 6)Br.sub.2-Ph, —NH-2,(3,4,5 or 6)I.sub.2-Ph, —NH-2,(3,4,5 or 6)Me.sub.2-Ph, —NH-2,(3,4,5 or 6)Et.sub.2-Ph, —NH-2,(3,4,5, or 6)Pr.sub.2-Ph, —NH-2,(3,4,5 or 6)Bu.sub.2-Ph, [0268] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0269] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0270] an —OH group or a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alcohol group (such as —CH.sub.2OH, —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH); [0271] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid group (such as —COOH, —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0272] a substituted or unsubstituted linear or branched carbonyl group (such as —(CO)Me, —(CO)Et, —(CO)Pr, —(CO)iPr, —(CO)nBu, —(CO)iBu, —(CO)tBu, —(CO)Ph, —(CO)CH.sub.2Ph, —(CO)CH.sub.2OH, —(CO)CH.sub.2OCH.sub.3, —(CO)CH.sub.2NH.sub.2, —(CO)CH.sub.2NHMe, —(CO)CH.sub.2NMe.sub.2, —(CO)-cyclopropyl, —(CO)-1,3-epoxypropan-2-yl; —(CO)NH.sub.2, —(CO)NHMe, —(CO)NMe.sub.2, —(CO)NHEt, —(CO)NEt.sub.2, —(CO)-pyrollidine-N-yl, —(CO)-morpholine-N-yl, —(CO)-piperazine-N-yl, —(CO)—N-methyl-piperazine-N-yl, —(CO)NHCH.sub.2CH.sub.2OH, —(CO)NHCH.sub.2CH.sub.2OMe, —(CO)NHCH.sub.2CH.sub.2NH.sub.2, —(CO)NHCH.sub.2CH.sub.2NHMe, and —(CO)NHCH.sub.2CH.sub.2NMe.sub.2; [0273] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid ester group (such as —COOMe, —COOEt, —COOPr, —COO-i-Pr, —COO-n-Bu, —COO-i-Bu, —COO-t-Bu, —CH.sub.2COOMe, —CH.sub.2CH.sub.2COOMe, —CH.sub.2CH.sub.2CH.sub.2COOMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOMe); [0274] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 amide group (such as —CO—NH.sub.2, —CO—NMeH, —CO—NMe.sub.2, —CO—NEtH, —CO—NEtMe, —CO—NEt.sub.2, —CO—NPrH, —CO—NPrMe, and —CO—NPrEt); [0275] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 amino carbonyl group (such as —NH—CO-Me, —NH—CO-Et, —NH—CO—Pr, —NH—CO-Bu, —NH—CO-pentyl, —NH—CO-hexyl, —NH—CO-Ph, —NMe-CO-Me, —NMe-CO-Et, —NMe-CO—Pr, —NMe-CO-Bu, —NMe-CO-pentyl, —NMe-CO-hexyl, —NMe-CO-Ph; [0276] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 alkoxy or aryloxy group (such as —OMe, —OEt, —OPr, —O-i-Pr, —O-n-Bu, —O-i-Bu, —O-t-Bu, —O-pentyl, —O-hexyl, —OCH.sub.2F, —OCHF.sub.2, —OCF.sub.3, —OCH.sub.2Cl, —OCHCl.sub.2, —OCCl.sub.3, —O-Ph, —O—CH.sub.2-Ph, —O—CH.sub.2-(2,3 or 4)-F-Ph, —O—CH.sub.2-(2,3 or 4)-Cl-Ph, —CH.sub.2OMe, —CH.sub.2OEt, —CH.sub.2OPr, —CH.sub.2OBu, —CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe); [0277] a substituted or unsubstituted linear or branched aminoalkoxy group (such as —OCH.sub.2NH.sub.2, —OCH.sub.2NHMe, —OCH.sub.2NMe.sub.2, —OCH.sub.2NHEt, —OCH.sub.2NEt.sub.2, —OCH.sub.2CH.sub.2NH.sub.2, —OCH.sub.2C H.sub.2NHMe, —OCH.sub.2CH.sub.2NMe.sub.2, —OCH.sub.2CH.sub.2NHEt, and —OCH.sub.2CH.sub.2NEt.sub.2; [0278] a substituted or unsubstituted sulphonyl group (such as —SO.sub.2Me, —SO.sub.2Et, —SO.sub.2Pr, —SO.sub.2iPr, —SO.sub.2Ph, —SO.sub.2-(2,3 or 4)-F-Ph, —SO.sub.2-cyclopropyl, —SO.sub.2CH.sub.2CH.sub.2OCH.sub.3), —SO.sub.2NH.sub.2, —SO.sub.2NHMe, —SO.sub.2NMe.sub.2, —SO.sub.2NHEt, —SO.sub.2NEt.sub.2, —SO.sub.2-pyrrolidine-N-yl, —SO.sub.2-morpholine-N-yl, —SO.sub.2NHCH.sub.2OMe, and —SO.sub.2NHCH.sub.2CH.sub.2OMe; [0279] a substituted or unsubstituted aminosulphonyl group (such as —NHSO.sub.2Me, —NHSO.sub.2Et, —NHSO.sub.2Pr, —NHSO.sub.2iPr, —NHSO.sub.2Ph, —NHSO.sub.2-(2,3 or 4)-F-Ph, —NHSO.sub.2-cyclopropyl, —NHSO.sub.2CH.sub.2CH.sub.2OCH.sub.3); [0280] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); [0281] a saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-1-yl, pyrrole-2-yl, pyrrole-3-yl, pyrazole-1-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-1-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-1-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-1-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-1-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-1-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-1-yl, tetrazole-2-yl, tetrazole-5-yl); [0282] preferably wherein R.sup.100, R.sup.101, R.sup.102, R.sup.103 R.sup.104, R.sup.105, R.sup.11, and R.sup.12, are each independently selected from H, a halogen (such as —F, —Cl, —Br, and —I), a substituted or unsubstituted C.sub.1-C.sub.6 alkyl group, —NH.sub.2 or a substituted or unsubstituted C.sub.1-C.sub.6 amino group, a substituted or unsubstituted C.sub.1-C.sub.6 alkoxy group, and a nitrile group; [0283] and wherein R.sup.21 and R.sup.22 are each independently selected from H and a group selected from the following groups: [0284] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0285] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0286] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, and —CH.sub.2CF.sub.3); [0287] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0288] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0289] a substituted or unsubstituted linear or branched C.sub.2-C.sub.6 alcohol group (such as —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH); [0290] a substituted or unsubstituted linear or branched C.sub.2-C.sub.6 carboxylic acid group (such as —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0291] a substituted or unsubstituted linear or branched carbonyl group (such as —(CO)Me, —(CO)Et, —(CO)Pr, —(CO)-i_Pr, —(CO)-n-Bu, —(CO)-i-Bu, —(CO)-t-Bu, —(CO)Ph, —(CO)CH.sub.2Ph, —(CO)CH.sub.2OH, —(CO)CH.sub.2OCH.sub.3, —(CO)CH.sub.2NH.sub.2, —(CO)CH.sub.2NHMe, —(CO)CH.sub.2NMe.sub.2, —(CO)-cyclopropyl, —(CO)-1,3-epoxypropan-2-yl; —(CO)NH.sub.2, —(CO)NHMe, —(CO)NMe.sub.2, —(CO)NHEt, —(CO)NEt.sub.2, —(CO)-pyrollidine-N-yl, —(CO)-morpholine-N-yl, —(CO)-piperazine-N-yl, —(CO)—N-methyl-piperazine-N-yl, —(CO)NHCH.sub.2CH.sub.2OH, —(CO)NHCH.sub.2CH.sub.2OMe, —(CO)NHCH.sub.2CH.sub.2NH.sub.2, —(CO)NHCH.sub.2CH.sub.2NHMe, and —(CO)NHCH.sub.2CH.sub.2NMe.sub.2; [0292] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid ester group (such as —COOMe, —COOEt, —COOPr, —COO-i-Pr, —COO-n-Bu, —COO-i-Bu, —COO-t-Bu, —CH.sub.2COOMe, —CH.sub.2CH.sub.2COOMe, —CH.sub.2CH.sub.2CH.sub.2COOMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOMe); [0293] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 amide group (such as —CO—NH.sub.2, —CO—NMeH, —CO—NMe.sub.2, —CO—NEtH, —CO—NEtMe, —CO—NEt.sub.2, —CO—NPrH, —CO—NPrMe, and —CO—NPrEt); [0294] a substituted or unsubstituted sulphonyl group (such as —SO.sub.2Me, —SO.sub.2Et, —SO.sub.2Pr, —SO.sub.2iPr, —SO.sub.2Ph, —SO.sub.2-(2,3 or 4)-F-Ph, —SO.sub.2— cyclopropyl, —SO.sub.2CH.sub.2CH.sub.2OCH.sub.3), —SO.sub.2NH.sub.2, —SO.sub.2NHMe, —SO.sub.2NMe.sub.2, —SO.sub.2NHEt, —SO.sub.2NEt.sub.2, —SO.sub.2-pyrrolidine-N-yl, —SO.sub.2-morpholine-N-yl, —SO.sub.2NHCH.sub.2OMe, and —SO.sub.2NHCH.sub.2CH.sub.2OMe; [0295] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); and [0296] a substituted or unsubstituted saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-2-yl, pyrrole-3-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-5-yl);
[0297] preferably wherein R.sup.21 and R.sup.22 are each a group independently selected from H and the following: [0298] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0299] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0300] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, and —CH.sub.2CF.sub.3; [0301] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0302] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0303] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); and [0304] a substituted or unsubstituted saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-2-yl, pyrrole-3-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-5-yl);
[0305] and wherein R.sup.3, and R.sup.5 are typically each independently selected from H and a group selected from the following groups: [0306] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0307] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0308] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, —CH.sub.2Cl, —CH.sub.2Br, —CH.sub.2I, —CF.sub.3, —CCl.sub.3—CBr.sub.3, —Cl.sub.3, —CH.sub.2CF.sub.3, —CH.sub.2CCl.sub.3, —CH.sub.2CBr.sub.3, and —CH.sub.2Cl.sub.3); [0309] —NH.sub.2 or a substituted or unsubstituted linear or branched primary secondary or tertiary C.sub.1-C.sub.6 amine group (such as —NMeH, —NMe.sub.2, —NEtH, —NEtMe, —NEt.sub.2, —NPrH, —NPrMe, —NPrEt, —NPr.sub.2, —NBuH, —NBuMe, —NBuEt, —CH.sub.2—NH.sub.2, —CH.sub.2—NMeH, —CH.sub.2—NMe.sub.2, —CH.sub.2—NEtH, —CH.sub.2—NEtMe, —CH.sub.2—NEt.sub.2, —CH.sub.2—NPrH, —CH.sub.2—NPrMe, and —CH.sub.2—NPrEt); [0310] a substituted or unsubstituted amino-aryl group (such as —NH-Ph, —NH-(2,3 or 4)F-Ph, —NH-(2,3 or 4)Cl-Ph, —NH-(2,3 or 4)Br-Ph, —NH-(2,3 or 4)I-Ph, —NH-(2,3 or 4)Me-Ph, —NH-(2,3 or 4)Et-Ph, —NH-(2,3 or 4)Pr-Ph, —NH-(2,3 or 4)Bu-Ph, NH-(2,3 or 4)OMe-Ph, —NH-(2,3 or 4)OEt-Ph, —NH-(2,3 or 4)OPr-Ph, —NH-(2,3 or 4)OBu-Ph, —NH-2,(3,4,5 or 6)F.sub.2-Ph, —NH-2,(3,4,5 or 6)Cl.sub.2-Ph, —NH-2,(3,4,5 or 6)Br.sub.2-Ph, —NH-2,(3,4,5 or 6)I.sub.2-Ph, —NH-2,(3,4,5 or 6)Me.sub.2-Ph, —NH-2,(3,4,5 or 6)Et.sub.2-Ph, —NH-2,(3,4,5, or 6)Pr.sub.2-Ph, —NH-2,(3,4,5 or 6)Bu.sub.2-Ph, [0311] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0312] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0313] an —OH group or a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alcohol group (such as —CH.sub.2OH, —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH); [0314] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid group (such as —COOH, —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0315] a substituted or unsubstituted linear or branched carbonyl group (such as —(CO)Me, —(CO)Et, —(CO)Pr, —(CO)iPr, —(CO)nBu, —(CO)iBu, —(CO)tBu, —(CO)Ph, —(CO)CH.sub.2Ph, —(CO)CH.sub.2OH, —(CO)CH.sub.2OCH.sub.3, —(CO)CH.sub.2NH.sub.2, —(CO)CH.sub.2NHMe, —(CO)CH.sub.2NMe.sub.2, —(CO)-cyclopropyl, —(CO)-1,3-epoxypropan-2-yl; —(CO)NH.sub.2, —(CO)NHMe, —(CO)NMe.sub.2, —(CO)NHEt, —(CO)NEt.sub.2, —(CO)-pyrollidine-N-yl, —(CO)-morpholine-N-yl, —(CO)-piperazine-N-yl, —(CO)—N-methyl-piperazine-N-yl, —(CO)NHCH.sub.2CH.sub.2OH, —(CO)NHCH.sub.2CH.sub.2OMe, —(CO)NHCH.sub.2CH.sub.2NH.sub.2, —(CO)NHCH.sub.2CH.sub.2NHMe, and —(CO)NHCH.sub.2CH.sub.2NMe.sub.2; [0316] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid ester group (such as —COOMe, —COOEt, —COOPr, —COO-i-Pr, —COO-n-Bu, —COO-i-Bu, —COO-t-Bu, —CH.sub.2COOMe, —CH.sub.2CH.sub.2COOMe, —CH.sub.2CH.sub.2CH.sub.2COOMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOMe); [0317] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 amide group (such as —CO—NH.sub.2, —CO—NMeH, —CO—NMe.sub.2, —CO—NEtH, —CO—NEtMe, —CO—NEt.sub.2, —CO—NPrH, —CO—NPrMe, and —CO—NPrEt); [0318] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 amino carbonyl group (such as —NH—CO-Me, —NH—CO-Et, —NH—CO—Pr, —NH—CO-Bu, —NH—CO-pentyl, —NH—CO-hexyl, —NH—CO-Ph, —NMe-CO-Me, —NMe-CO-Et, —NMe-CO—Pr, —NMe-CO-Bu, —NMe-CO-pentyl, —NMe-CO-hexyl, —NMe-CO-Ph; [0319] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 alkoxy or aryloxy group (such as —OMe, —OEt, —OPr, —O-i-Pr, —O-n-Bu, —O-i-Bu, —O-t-Bu, —O-pentyl, —O-hexyl, —OCH.sub.2F, —OCHF.sub.2, —OCF.sub.3, —OCH.sub.2Cl, —OCHCl.sub.2, —OCCl.sub.3, —O-Ph, —O—CH.sub.2-Ph, —O—CH.sub.2-(2,3 or 4)-F-Ph, —O—CH.sub.2-(2,3 or 4)-Cl-Ph, —CH.sub.2OMe, —CH.sub.2OEt, —CH.sub.2Pr, —CH.sub.2OBu, —CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe); [0320] a substituted or unsubstituted linear or branched aminoalkoxy group (such as —OCH.sub.2NH.sub.2, —OCH.sub.2NHMe, —OCH.sub.2NMe.sub.2, —OCH.sub.2NHEt, —OCH.sub.2NEt.sub.2, —OCH.sub.2CH.sub.2NH.sub.2, —OCH.sub.2C H.sub.2NHMe, —OCH.sub.2CH.sub.2NMe.sub.2, —OCH.sub.2CH.sub.2NHEt, and —OCH.sub.2CH.sub.2NEt.sub.2; [0321] a substituted or unsubstituted sulphonyl group (such as —SO.sub.2Me, —SO.sub.2Et, —SO.sub.2Pr, —SO.sub.2iPr, —SO.sub.2Ph, —SO.sub.2-(2,3 or 4)-F-Ph, —SO.sub.2— cyclopropyl, —SO.sub.2CH.sub.2CH.sub.2OCH.sub.3), —SO.sub.2NH.sub.2, —SO.sub.2NHMe, —SO.sub.2NMe.sub.2, —SO.sub.2NHEt, —SO.sub.2NEt.sub.2, —SO.sub.2-pyrrolidine-N-yl, —SO.sub.2-morpholine-N-yl, —SO.sub.2NHCH.sub.2OMe, and —SO.sub.2NHCH.sub.2CH.sub.2OMe; [0322] a substituted or unsubstituted aminosulphonyl group (such as —NHSO.sub.2Me, —NHSO.sub.2Et, —NHSO.sub.2Pr, —NHSO.sub.2iPr, —NHSO.sub.2Ph, —NHSO.sub.2-(2,3 or 4)-F-Ph, —NHSO.sub.2-cyclopropyl, —NHSO.sub.2CH.sub.2CH.sub.2OCH.sub.3); [0323] a substituted or unsubstituted aromatic group (such as Ph-, 2-F-Ph-, 3-F-Ph-, 4-F-Ph-, 2-Cl-Ph-, 3-Cl-Ph-, 4-Cl-Ph-, 2-Br-Ph-, 3-Br-Ph-, 4-Br-Ph-, 2-I-Ph-, 3-I-Ph, 4-I-Ph-, 2,(3,4,5 or 6)-F.sub.2-Ph-, 2,(3,4,5 or 6)-Cl.sub.2-Ph-, 2,(3,4,5 or 6)-Br.sub.2-Ph-, 2,(3,4,5 or 6)-I.sub.2-Ph-, 2,(3,4,5 or 6)-Me.sub.2-Ph-, 2,(3,4,5 or 6)-Et.sub.2-Ph-, 2,(3,4,5 or 6)-Pr.sub.2-Ph-, 2,(3,4,5 or 6)-Bu.sub.2-Ph-, 2,(3,4,5 or 6)-(CN).sub.2-Ph-, 2,(3,4,5 or 6)-(NO.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(NH.sub.2).sub.2-Ph-, 2,(3,4,5 or 6)-(MeO).sub.2-Ph-, 2,(3,4,5 or 6)-(CF.sub.3).sub.2-Ph-, 3,(4 or 5)-F.sub.2-Ph-, 3,(4 or 5)-Cl.sub.2-Ph-, 3,(4 or 5)-Br.sub.2-Ph-, 3,(4 or 5)-I.sub.2-Ph-, 3,(4 or 5)-Me.sub.2-Ph-, 3,(4 or 5)-Et.sub.2-Ph-, 3,(4 or 5)-Pr.sub.2-Ph-, 3,(4 or 5)-Bu.sub.2-Ph-, 3,(4 or 5)-(CN).sub.2-Ph-, 3,(4 or 5)-(NO.sub.2).sub.2-Ph-, 3,(4 or 5)-(NH.sub.2).sub.2-Ph-, 3,(4 or 5)-(MeO).sub.2-Ph-, 3,(4 or 5)-(CF.sub.3).sub.2-Ph-, 2-Me-Ph-, 3-Me-Ph-, 4-Me-Ph-, 2-Et-Ph-, 3-Et-Ph-, 4-Et-Ph-, 2-Pr-Ph-, 3-Pr-Ph-, 4-Pr-Ph-, 2-Bu-Ph-, 3-Bu-Ph-, 4-Bu-Ph-, 2-(CN)-Ph-, 3-(CN)-Ph-, 4-(CN)-Ph-, 2-(NO.sub.2)-Ph-, 3-(NO.sub.2)-Ph-, 4-(NO.sub.2)-Ph-, 2-(NH.sub.2)-Ph-, 3-(NH.sub.2)-Ph-, 4-(NH.sub.2)-Ph-, 2-MeO-Ph-, 3-MeO-Ph-, 4-MeO-Ph-, 2-(NH.sub.2—CO)-Ph-, 3-(NH.sub.2—CO)-Ph-, 4-(NH.sub.2—CO)-Ph-, 2-CF.sub.3-Ph-, 3-CF.sub.3-Ph-, 4-CF.sub.3-Ph-, 2-CF.sub.3O-Ph-, 3-CF.sub.3O-Ph-, and 4-CF.sub.3O-Ph-); [0324] a saturated or unsaturated, substituted or unsubstituted, heterocyclic group including an aromatic heterocyclic group and/or a non-aromatic heterocyclic group (such as pyrrole-1-yl, pyrrole-2-yl, pyrrole-3-yl, pyrazole-1-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-1-yl, imidazole-2-yl, imidazole-4-yl, imidazole-5-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-4-yl, 1,2,3-triazole-5-yl, 1,2,4-triazole-1-yl, 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazine-3-yl, pyridazine-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, pyrazine-2-yl, pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-1-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-1-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-1-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiophen-2-yl, thiophen-3-yl, isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, thiane-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, furazan-3-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,2,4-oxadiazol)-3-yl, (1,2,4-oxadiazol)-5-yl; and tetrazole-1-yl, tetrazole-2-yl, tetrazole-5-yl);
[0325] preferably wherein R.sup.5 is independently selected from H and a group selected from the following groups: [0326] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl group (such as Me, Et, Pr, i-Pr, n-Bu, i-Bu, t-Bu, pentyl and hexyl); [0327] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alkyl-aryl group (such as —CH.sub.2Ph, —CH.sub.2(2,3 or 4)F-Ph, —CH.sub.2(2,3 or 4)Cl-Ph, —CH.sub.2(2,3 or 4)Br-Ph, —CH.sub.2(2,3 or 4)I-Ph, —CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2Ph); [0328] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 halogenated alkyl group (such as —CH.sub.2F, —CH.sub.2Cl, —CH.sub.2Br, —CH.sub.2I, —CF.sub.3, —CCl.sub.3—CBr.sub.3, —Cl.sub.3, —CH.sub.2CF.sub.3, —CH.sub.2CCl.sub.3, —CH.sub.2CBr.sub.3, and —CH.sub.2CI.sub.3); [0329] —NH.sub.2 or a substituted or unsubstituted linear or branched primary secondary or tertiary C.sub.1-C.sub.6 amine group (such as —NMeH, —NMe.sub.2, —NEtH, —NEtMe, —NEt.sub.2, —NPrH, —NPrMe, —NPrEt, —NPr.sub.2, —NBuH, —NBuMe, —NBuEt, —CH.sub.2—NH.sub.2, —CH.sub.2—NMeH, —CH.sub.2—NMe.sub.2, —CH.sub.2—NEtH, —CH.sub.2—NEtMe, —CH.sub.2—NEt.sub.2, —CH.sub.2—NPrH, —CH.sub.2—NPrMe, and —CH.sub.2—NPrEt); [0330] a substituted or unsubstituted amino-aryl group (such as —NH-Ph, —NH-(2,3 or 4)F-Ph, —NH-(2,3 or 4)Cl-Ph, —NH-(2,3 or 4)Br-Ph, —NH-(2,3 or 4)I-Ph, —NH-(2,3 or 4)Me-Ph, —NH-(2,3 or 4)Et-Ph, —NH-(2,3 or 4)Pr-Ph, —NH-(2,3 or 4)Bu-Ph, NH-(2,3 or 4)OMe-Ph, —NH-(2,3 or 4)OEt-Ph, —NH-(2,3 or 4)OPr-Ph, —NH-(2,3 or 4)OBu-Ph, —NH-2,(3,4,5 or 6)F.sub.2-Ph, —NH-2,(3,4,5 or 6)Cl.sub.2-Ph, —NH-2,(3,4,5 or 6)Br.sub.2-Ph, —NH-2,(3,4,5 or 6)I.sub.2-Ph, —NH-2,(3,4,5 or 6)Me.sub.2-Ph, —NH-2,(3,4,5 or 6)Et.sub.2-Ph, —NH-2,(3,4,5, or 6)Pr.sub.2-Ph, —NH-2,(3,4,5 or 6)Bu.sub.2-Ph, [0331] a substituted or unsubstituted cyclic amine or amido group (such as pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, 2-keto-pyrrolidinyl, 3-keto-pyrrolidinyl, 2-keto-piperidinyl, 3-keto-piperidinyl, and 4-keto-piperidinyl); [0332] a substituted or unsubstituted cyclic C.sub.3-C.sub.8 alkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl); [0333] an —OH group or a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 alcohol group (such as —CH.sub.2OH, —CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2OH, —CH.sub.2CH.sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH.sub.2CH.sub.2OH, —CH(CH.sub.3)CH(CH.sub.3)OH, —CH(CH.sub.2CH.sub.3)CH.sub.2OH, —C(CH.sub.3).sub.2CH.sub.2OH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OH); [0334] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid group (such as —COOH, —CH.sub.2COOH, —CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2COOH, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOH); [0335] a substituted or unsubstituted linear or branched carbonyl group (such as —(CO)Me, —(CO)Et, —(CO)Pr, —(CO)iPr, —(CO)nBu, —(CO)iBu, —(CO)tBu, —(CO)Ph, —(CO)CH.sub.2Ph, —(CO)CH.sub.2OH, —(CO)CH.sub.2OCH.sub.3, —(CO)CH.sub.2NH.sub.2, —(CO)CH.sub.2NHMe, —(CO)CH.sub.2NMe.sub.2, —(CO)-cyclopropyl, —(CO)-1,3-epoxypropan-2-yl; —(CO)NH.sub.2, —(CO)NHMe, —(CO)NMe.sub.2, —(CO)NHEt, —(CO)NEt.sub.2, —(CO)-pyrollidine-N-yl, —(CO)-morpholine-N-yl, —(CO)-piperazine-N-yl, —(CO)—N-methyl-piperazine-N-yl, —(CO)NHCH.sub.2CH.sub.2OH, —(CO)NHCH.sub.2CH.sub.2OMe, —(CO)NHCH.sub.2CH.sub.2NH.sub.2, —(CO)NHCH.sub.2CH.sub.2NHMe, and —(CO)NHCH.sub.2CH.sub.2NMe.sub.2; [0336] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 carboxylic acid ester group (such as —COOMe, —COOEt, —COOPr, —COO-i-Pr, —COO-n-Bu, —COO-i-Bu, —COO-t-Bu, —CH.sub.2COOMe, —CH.sub.2CH.sub.2COOMe, —CH.sub.2CH.sub.2CH.sub.2COOMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2COOMe); [0337] a substituted or unsubstituted linear or branched C.sub.1-C.sub.6 amide group (such as —CO—NH.sub.2, —CO—NMeH, —CO—NMe.sub.2, —CO—NEtH, —CO—NEtMe, —CO—NEt.sub.2, —CO—NPrH, —CO—NPrMe, and —CO—NPrEt); [0338] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 amino carbonyl group (such as —NH—CO-Me, —NH—CO-Et, —NH—CO—Pr, —NH—CO-Bu, —NH—CO-pentyl, —NH—CO-hexyl, —NH—CO-Ph, —NMe-CO-Me, —NMe-CO-Et, —NMe-CO—Pr, —NMe-CO-Bu, —NMe-CO-pentyl, —NMe-CO-hexyl, —NMe-CO-Ph; [0339] a substituted or unsubstituted linear or branched C.sub.1-C.sub.7 alkoxy or aryloxy group (such as —OMe, —OEt, —OPr, —O-i-Pr, —O-n-Bu, —O-i-Bu, —O-t-Bu, —O-pentyl, —O-hexyl, —OCH.sub.2F, —OCHF.sub.2, —OCF.sub.3, —OCH.sub.2Cl, —OCHCl.sub.2, —OCCl.sub.3, —O-Ph, —O—CH.sub.2-Ph, —O—CH.sub.2-(2,3 or 4)-F-Ph, —O—CH.sub.2-(2,3 or 4)-Cl-Ph, —CH.sub.2OMe, —CH.sub.2OEt, —CH.sub.2OPr, —CH.sub.2OBu, —CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2OMe, —CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe, and —CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2OMe); [0340] a substituted or unsubstituted linear or branched aminoalkoxy group (such as —OCH.sub.2NH.sub.2, —OCH.sub.2NHMe, —OCH.sub.2NMe.sub.2, —OCH.sub.2NHEt, —OCH.sub.2NEt.sub.2, —OCH.sub.2CH.sub.2NH.sub.2, —OCH.sub.2C H.sub.2NHMe, —OCH.sub.2CH.sub.2NMe.sub.2, —OCH.sub.2CH.sub.2NHEt, and —OCH.sub.2CH.sub.2NEt.sub.2; [0341] a substituted or unsubstituted sulphonyl group (such as —SO.sub.2Me, —SO.sub.2Et, —SO.sub.2Pr, —SO.sub.2iPr, —SO.sub.2Ph, —SO.sub.2-(2,3 or 4)-F-Ph, —SO.sub.2-cyclopropyl, —SO.sub.2CH.sub.2CH.sub.2OCH.sub.3), —SO.sub.2NH.sub.2, —SO.sub.2NHMe, —SO.sub.2NMe.sub.2, —SO.sub.2NHEt, —SO.sub.2NEt.sub.2, —SO.sub.2-pyrrolidine-N-yl, —SO.sub.2-morpholine-N-yl, —SO.sub.2NHCH.sub.2OMe, and —SO.sub.2NHCH.sub.2CH.sub.2OMe; [0342] a substituted or unsubstituted aminosulphonyl group (such as —NHSO.sub.2Me, —NHSO.sub.2Et, —NHSO.sub.2Pr, —NHSO.sub.2iPr, —NHSO.sub.2Ph, —NHSO.sub.2-(2,3 or 4)-F-Ph, —NHSO.sub.2-cyclopropyl, —NHSO.sub.2CH.sub.2CH.sub.2OCH.sub.3); [0343] a saturated or unsaturated, substituted or unsubstituted, non-aromatic heterocyclic group (such as pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, 2-azapiperidine-1-yl, 2-azapiperidine-3-yl, 2-azapiperidine-4-yl, 3-azapiperidine-1-yl, 3-azapiperidine-2-yl, 3-azapiperidine-4-yl, 3-azapiperidine-5-yl, piperazine-1-yl, piperazine-2-yl, furan-2-yl, furan-3-yl, pyran-2-yl, pyran-3-yl, pyran-4-yl, 2-azapyran-2-yl, 2-azapyran-3-yl, 2-azapyran-4-yl, 2-azapyran-5-yl, 2-azapyran-6-yl, 3-azapyran-2-yl, 3-azapyran-4-yl, 3-azapyran-5-yl, 3-azapyran-6-yl, 4-azapyran-2-yl, 4-azapyran-3-yl, 4-azapyran-4-yl, 4-azapyran-5-yl, 4-azapyran-6-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-2-yl, 2-aza-tetrahydrofuran-3-yl, 2-aza-tetrahydrofuran-4-yl, 2-aza-tetrahydrofuran-5-yl, 3-aza-tetrahydrofuran-2-yl, 3-aza-tetrahydrofuran-3-yl, 3-aza-tetrahydrofuran-4-yl, 3-aza-tetrahydrofuran-5-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, 2-aza-tetrahydropyran-2-yl, 2-aza-tetrahydropyran-3-yl, 2-aza-tetrahydropyran-4-yl, 2-aza-tetrahydropyran-5-yl, 2-aza-tetrahydropyran-6-yl, 3-aza-tetrahydropyran-2-yl, 3-aza-tetrahydropyran-3-yl, 3-aza-tetrahydropyran-4-yl, 3-aza-tetrahydropyran-5-yl, 3-aza-tetrahydropyran-6-yl, morpholine-2-yl, morpholine-3-yl, morpholine-4-yl, thiopyran-2-yl, thiopyran-3-yl, thiopyran-4-yl, 2-azathiopyran-2-yl, 2-azathiopyran-3-yl, 2-azathiopyran-4-yl, 2-azathiopyran-5-yl, 2-azathiopyran-6-yl, 3-azathiopyran-2-yl, 3-azathiopyran-4-yl, 3-azathiopyran-5-yl, 3-azathiopyran-6-yl, 4-azathiopyran-2-yl, 4-azathiopyran-3-yl, 4-azathiopyran-4-yl, 4-azathiopyran-5-yl, 4-azathiopyran-6-yl, thiolane-2-yl, thiolane-3-yl, thiane-2-yl, thiane-3-yl, and thiane-4-yl); and [0344] where there are one or two R groups attached to the same atom, they may together form a group which is double bonded to that atom, (such as a carbonyl group (═O) or an alkene group (═C(R′).sub.2) (wherein each R′ group is the same or different and is H or an organic group, preferably H or a straight or branched C.sub.1-C.sub.6 alkyl group));
[0345] preferably wherein, R.sup.3 and R.sup.5 may each be selected independently from: H, a substituted or unsubstituted C.sub.1-C.sub.6 alkyl group, an —NH.sub.2 or a substituted or unsubstituted C.sub.1-C.sub.6 amino group, a substituted or unsubstituted C.sub.1-C.sub.6 alkoxy group, and a nitrile group.
[0346] Thus, the present invention provides a TDO or IDO inhibitor compound for use in medicine, which compound comprises a formula selected from one of the following:
##STR00020## ##STR00021## ##STR00022## ##STR00023## ##STR00024## ##STR00025## ##STR00026## ##STR00027## ##STR00028## ##STR00029## ##STR00030## ##STR00031## ##STR00032##
[0347] Typically, the above formulae (and all formulae herein) are shown in non-stereoisomeric form. For the avoidance of doubt, throughout the present disclosure a single formula is intended to represent all possible stereoisomers of a particular structure, including all possible isolated enantiomers corresponding to the formula, all possible mixtures of enantiomers corresponding to the formula, all possible mixtures of diastereomers corresponding to the formula, all possible mixtures of epimers corresponding to the formula and all possible racemic mixtures corresponding to the formula. In addition to this, the above formulae (and all formulae herein) are intended to represent all tautomeric forms equivalent to the corresponding formulae.
[0348] In the context of the present invention, the medicinal use is not especially limited, provided that it is a use which is facilitated by the TDO and/or the IDO inhibitory effect of the compound. Thus, the compounds of the invention may be for use in any disease, condition or disorder that may be prevented, ameliorated or treated using a TDO and/or IDO inhibitor. Typically this comprises a disease condition and/or a disorder selected from: a cancer, an inflammatory condition, an infectious disease, a central nervous system disease or disorder, coronary heart disease, chronic renal failure, post anaesthesia cognitive dysfunction, a disease condition and/or a disorder relating to female reproductive health including contraception or abortion, and cataracts.
[0349] When the disease, condition or disorder is an inflammatory disease, condition or disorder, it is not especially limited, provided that the disease, condition or disorder is one which may be treated, prevented or ameliorated by using a TDO and/or IDO inhibitor. However, typically the inflammatory condition is a condition relating to immune B cell, T cell, dendritic cell, natural killer cell, macrophage, and/or neutrophil dysregulation.
[0350] When the disease, condition or disorder is a cancer, it is not especially limited, provided that the cancer is one which may be treated, prevented or ameliorated by using a TDO and/or IDO inhibitor. Thus the cancer may be a cancer selected from: a solid or liquid tumour including cancer of the eye, brain (such as gliomas, glioblastomas, medullablastomas, craniopharyngioma, ependymoma, and astrocytoma), spinal cord, kidney, mouth, lip, throat, oral cavity, nasal cavity, small intestine, colon, parathyroid gland, gall bladder, head and neck, breast, bone, bile duct, cervix, heart, hypopharyngeal gland, lung, bronchus, liver, skin, ureter, urethra, testicles, vagina, anus, laryngeal gland, ovary, thyroid, oesophagus, nasopharyngeal gland, pituitary gland, salivary gland, prostate, pancreas, adrenal glands; an endometrial cancer, oral cancer, melanoma, neuroblastoma, gastric cancer, an angiomatosis, a hemangioblastoma, a pheochromocytoma, a pancreatic cyst, a renal cell carcinoma, Wilms' tumour, squamous cell carcinoma, sarcoma, osteosarcoma, Kaposi sarcoma, rhabdomyosarcoma, hepatocellular carcinoma, PTEN Hamartoma-Tumor Syndromes (PHTS) (such as Lhermitte-Duclos disease, Cowden syndrome, Proteus syndrome, and Proteus-like syndrome), leukaemias and lymphomas (such as acute lymphoblastic leukaemia, chronic lymphocytic leukaemia, acute myelogenous leukaemia, chronic myelogenous leukaemia, hairy cell leukaemia, T-cell prolymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, adult T-cell leukemia, juvenile myelomonocytic leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, mantle lymphoma, follicular lymphoma, primary effusion lymphoma, AIDS-related lymphoma, Hodgkin lymphoma, diffuse B cell lymphoma, Burkitt lymphoma, and cutaneous T-cell lymphoma). However, when the compound is an IDO inhibitor, typically (but not exclusively) the cancer is a cancer selected from acute myeloid leukemia (AML), a small-cell lung cancer, a melanoma, an ovarian cancer, a colorectal cancer, a pancreatic cancer, an endometrial cancer, and a skin papilloma. When the compound is a TDO inhibitor, typically (but not exclusively) the cancer is a cancer selected from a glioma, and a hepatocellular carcinoma.
[0351] When the disease is an infectious disease, it is not especially limited, provided that the disease is one which may be treated, prevented or ameliorated by using a TDO and/or IDO inhibitor. However, typically the infectious disease is selected from a bacterial infection and a viral infection, preferably a gut infection, sepsis, and sepsis induced hypotension.
[0352] When the disease, condition or disorder is a central nervous system disease, condition or disorder, it is not especially limited, provided that the disease, condition or disorder is one which may be treated, prevented or ameliorated by using a TDO and/or IDO inhibitor. However, the central nervous system disease, condition or disorder is typically selected from amyotrophic lateral sclerosis (AML), Huntington's disease, Alzheimer's disease, pain, a psychiatric disorder, multiple sclerosis, Parkinson's disease, and HIV related neurocognitive decline.
[0353] When the disease, condition or disorder is one relating to female reproductive health, it is not especially limited provided that the disease, condition or disorder is one which may be treated, prevented or ameliorated by using a TDO and/or IDO inhibitor. In typical embodiments the disease, condition or disorder is selected from gynaecological disorders such as endometriosis. Conditions relating to female reproductive health that are included in the invention include contraception and abortion such that the compounds of the invention may be used as a contraceptive and/or abortive agent.
[0354] The present invention also provides a pharmaceutical composition comprising a compound as defined above. Whilst the pharmaceutical composition is not especially limited, typically the composition further comprises a pharmaceutically acceptable additive and/or excipient. In the pharmaceutical composition, the compound as defined above may be present in the form described above, but may alternatively be in a form suitable for improving bioavailability, solubility, and/or activity, and/or may be in a form suitable for improving formulation. Thus, the compound may be in the form of a pharmaceutically acceptable salt, hydrate, acid, ester, or other alternative suitable form. Typically, the composition is for treating a disease, condition or disorder as defined above. In some instances, the compound may be present in the composition as a pharmaceutically acceptable salt, or other alternative form of the compound, in order to ameliorate pharmaceutical formulation.
[0355] In some embodiments the pharmaceutical composition is a composition for treating a cancer, further comprising a further agent for treating cancer. The further agent for treating cancer is not especially limited, provided that it affords some utility for cancer treatment. However, typically the further agent for treating cancer is selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormone analogues, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, immunotherapeutic agents, proapoptotic agents and cell cycle signalling inhibitors. An immunotherapeutic agent may consist of but is not limited to an anti-tumour vaccine, an oncolytic virus, an immune stimulatory antibody such as anti-CTLA4, anti-PD1, anti-PDL-1, anti-OX40, anti-41BB, anti-CD27, anti-CD40, anti-LAG3, anti-TIM3, and anti-GITR, a novel adjuvant, a peptide, a cytokine, a chimeric antigen receptor T cell therapy (CAR-T), a small molecule immune modulator, tumour microenvironment modulators, and anti-angiogenic agents.
[0356] In still further embodiments the invention provides a pharmaceutical kit for treating a cancer, which pharmaceutical kit comprises: [0357] (a) a compound as defined above; and [0358] (b) a further agent for treating cancer; preferably wherein the further agent for treating cancer is selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormone analogues, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, immunotherapeutic agents, proapoptotic agents and cell cycle signalling inhibitors;
[0359] wherein the compound and the further agent are suitable for administration simultaneously, sequentially or separately.
[0360] Further provided by the invention is a method of treating a disease and/or a condition and/or a disorder, which method comprises administering to a patient (or subject) a compound, or a composition, or a kit as defined above. The method is typically a method for treating any disease condition or disorder mentioned herein. In typical embodiments, the method is a method for treating a cancer. Preferably such a method comprises administering to a patient (or subject) a compound or a composition as defined above and a further agent for treating cancer as defined above. The compound or composition and the further agent may administered simultaneously, sequentially or separately, depending upon the agents and patients involved, and the type of cancer indicated.
[0361] Typically, in all embodiments of the invention, both above and below, the patient (or subject) is an animal, typically a mammal, and more typically a human.
[0362] Further provided by the invention is a method of synthesis of a compound as defined above, which method comprises a ring closing step to form the five-membered ring corresponding to ring Q in the compounds of the present invention.
[0363] In typical embodiments, this method of synthesis is carried out by reacting under conditions suitable for a condensation reaction. The skilled person may select the reaction conditions, with reference to known synthesis techniques depending on the appropriate starting materials. In some embodiments, the method comprises one or more additional substitution steps. The skilled person may select the reaction conditions, with reference to known synthesis techniques. An exemplary synthesis is shown in the Examples herein.
[0364] In addition to compounds for use in medicine, the present invention, and in particular the synthetic method, provides compounds that were not previously known, such compounds comprising a formula selected from one of the following:
##STR00033## ##STR00034## ##STR00035## ##STR00036## ##STR00037## ##STR00038## ##STR00039## ##STR00040##
[0365] Typically, the above formulae (and all formulae herein) are shown in non-stereoisomeric form. For the avoidance of doubt, throughout the present disclosure a single formula is intended to represent all possible stereoisomers of a particular structure, including all possible isolated enantiomers corresponding to the formula, all possible mixtures of enantiomers corresponding to the formula, all possible mixtures of diastereomers corresponding to the formula, all possible mixtures of epimers corresponding to the formula and all possible racemic mixtures corresponding to the formula. In addition to this, the above formulae (and all formulae herein) are intended to represent all tautomeric forms equivalent to the corresponding formula.
[0366] The invention will now be described in more detail, by way of example only, with reference to the following specific embodiments.
EXAMPLES
Example 1—Methods of Synthesis
[0367] In order to demonstrate an exemplary method for synthesising the compounds of the present invention (depicting the ring closing step for ring Q), the following synthesis was carried out.
##STR00041##
Example 2—Assays
[0368] Exemplary compounds of the invention were prepared, and tested to determine their effect as TDO and/or IDO inhibitors. Two different assays were employed: 1. a cell-based assay for detecting the effect of test compounds on kynurenine production in two different cancer cell types. This assay utilised cancer cells which expressed either TDO (A172) or IDO (SKOV3) and as such was used as a means of testing compound activity at these two enzymes in a cell-based context. 2. a TDO and IDO biochemical coupled assay which utilised recombinantly produced and purified TDO and IDO enzymes in combination with the enzyme formamidase. This coupled enzyme system allowed conversion of N-formylkynurenine produced by TDO or IDO activity to kynurenine which was then quantified by fluorescence following addition of Erhlich's Reagent The protocols for these are set out below.
[0369] Cell Based Assay for Detection of Kynurenine Produced by TDO and/or IDO
[0370] A172 (human glioblastoma) and SKOV3 (human ovarian adenocarcinoma) cells were seeded in a 96 well plate at 30,000 or 40,000 cells per well respectively in phenol red-free RPMI supplemented with 10% FCS, 2 mM L-glutamine and 500 M L-tryptophan. IDO expression was induced in the SKOV3 cells by the addition of 500 ng/ml IFN-γ. Cells were incubated at 37° C. with or without the addition of test compound. After 48 hours, the cells were removed by centrifugation and Erhlich's reagent was added to the supernatant. The Erhlich's reagent was incubated for 5 minutes before the absorbance was read at 490 nM.
[0371] TDO and IDO Biochemical Coupled Assay
[0372] Recombinant human IDO or TDO was incubated in 50 mM KPO4 (pH 7.0), 0.5 mM EGTA, 0.5 mM EDTA, 0.05% Triton™ X100, 20 mM ascorbate, 10 M methylene blue, 500 U/ml catalase, 50 μg/ml KynB (kynurenine formamidase). TDO assays were carried out in the presence of 330 μM L-tryptophan, while IDO assays had the addition of 45 M L-tryptophan. After incubation for 17 minutes at room temperature the reactions were stopped by the addition of Erhlich's reagent and incubated at room temperature for 5 minutes before the fluorescence was read (Ex475, Em530).
[0373] The pIC50 values for a variety of test compounds are shown in Table 1 and Table 2.
TABLE-US-00001 TABLE 1 pIC50 values for Kynurenine cell-based assays determined for test compounds A172 Kynurenine SKOV3 Kynurenine cell based cell based Compound assay pIC50 assay pIC50 1 +++ ++ 2 +++ ++ 3 +++ ++ 4 ++ ++ 5 +++ ++ 6 ++ +/− 7 +++ ++ 8 +/− ++ 9 ++ + 10 ++ + 11 ++ + 12 +++ ++ 13 +++ ++ 14 ++ ++ 15 + ++ 16 ++ ++ 17 ++ + 18 ++ ++ 19 + ++ 20 ++ ++ 21 ++ ++ 22 ++ ++ 23 ++ +/− 24 ++ ++ 25 +++ ++ 26 + ++ 27 ++ ++ 28 +++ ++ 29 + ++ 30 ++ + 31 +/− ++ 32 +/− + 33 + +/− 34 ++ ++ 35 ++ + 36 ++ + 37 ++ ++ 38 ++ + 39 + ++ 40 +++ ++ 41 +++ ++ 42 +++ + 43 +++ ++ 44 +++ ++ 45 +++ + 46 ++ + 47 ++ + 48 ++ +/− 49 +++ ++ 50 ++ ++ 51 ++ ++ 52 + +++ 53 + ++ 54 + ++ 55 +/− + 56 +/− ++ 57 +++ ++ 58 ++ + 59 +/− + 60 ++ + 61 + +/− 62 ++ ++ 63 +++ ++ 64 ++ + 65 +++ ++ 66 ++ +/− 67 +/− + 68 ++ + 69 +++ + 70 ++ ++ 71 ++ + 72 +/− + 73 +++ ++ 74 + + 75 +++ + 76 ++ + 77 +/− + 78 ++ + 79 +/− ++ 80 +/− + 81 +++ ++ 82 +++ + Key: +++ = pIC.sub.50 ≧ 5.50 ++ = pIC.sub.50 4.50-5.49 + = pIC.sub.50 4.00-4.49 +/− = pIC.sub.50 < 4.00 NT = not tested
TABLE-US-00002 TABLE 2 pIC50 values for IDO and TDO inhibition determined for test compounds hIDO biochemical hTDO biochemical Compound assay pIC50 assay pIC50 1 ++ ++ 5 ++ + 7 ++ ++ 13 ++ + 17 + + 26 +++ +/− 34 ++ ++ 49 +/− + 50 ++ NT 63 + +/− 75 ++ ++ 80 ++ +/− 81 + +/− Key: +++ = pIC.sub.50 ≧ 5.50 ++ = pIC.sub.50 4.50-5.49 + = pIC.sub.50 4.00-4.49 +/− = pIC.sub.50 < 4.00 NT = not tested
[0374] The Tables show that a large number of the test compounds show strong TDO and IDO inhibitory function.