Abstract: Disclosed are tricyclic heterocyclic compounds having kinase inhibitory activity, pharmaceutical compositions and kits comprising the compounds, and use of the compounds in the treatment of or in medicaments for the treatment of various diseases and conditions. In particular, disclosed are tricyclic heterocyclic compounds of the formula (I) having CSF-1R (c-FMS kinase) inhibitory activity and their use in the treatment of various diseases and conditions, such as those mediated by CSF-1R, including proliferative or neoplastic diseases and conditions, including cancers, and bone, inflammatory, and autoimmune diseases and conditions.

Abstract: Disclosed are tricyclic heterocyclic compounds having kinase inhibitory activity, pharmaceutical compositions and kits comprising the compounds, and use of the compounds in the treatment of or in medicaments for the treatment of various diseases and conditions. In particular, disclosed are tricyclic heterocyclic compounds of the formula (I) having CSF-1R (c-FMS kinase) inhibitory activity and their use in the treatment of various diseases and conditions, such as those mediated by CSF-1R, including proliferative or neoplastic diseases and conditions, including cancers, and bone, inflammatory, and autoimmune diseases and conditions.

Abstract: pa The present invention relates to ketamine derivatives of the formula (I), pharmaceutical compositions comprising them, and methods for treating pain comprising administering them, and their use in the manufacture of medicaments for treating pain. The present invention also relates to methods for anaesthetizing and methods for sedating a subject comprising administering ketamine derivatives of the formula (II).

Abstract: The present invention relates to ketamine derivatives of the formula (I), pharmaceutical compositions comprising them, and methods for treating pain comprising administering them, and their use in the manufacture of medicaments for treating pain. The present invention also relates to methods for anaesthetizing and methods for sedating a subject comprising administering ketamine derivatives of the formula (II).

Abstract: Compounds of formula (1a) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, —C1-Cealkyl, —C1-Ceaminoalkyl, —C1-C6hydroxyalkyl, -haloC1-C6alkyl, —C1-C6alkoxyl, -haloC1—C<aIkoxyl, heteroaryl, aryl, hydroxyl, —C(0)Ci-C6alkyl, —OC(0)Ci-C6alkyl, —CH2OC(O)CrC6alkyl, —C(O)OC1, —C6alkyI, —NHC(O)C1, —C6alkyl, —NHS(O)2C1-C6alkyl, —S(O)2C1-C6alkyl, —S(O)2NH2, and —C(O)NJJ; Ring B is a 6-10 membered arylene or a 5-6 membered heteroarylene comprising at least one heteroatom selected from N, 0 or S; and wherein the aryl or heteroaryl is optionally, substituted wit

Abstract: The present invention relates to ketamine derivatives of the formula (I), pharmaceutical compositions comprising them, and methods for treating pain comprising administering them, and their use in the manufacture of medicaments for treating pain. The present invention also relates to methods for anaesthetizing and methods for sedating a subject comprising administering ketamine derivatives of the formula (II).

Abstract: The invention provides kinase inhibitors of Formula I: wherein either: (1) R1 is H, and (a) R2 is (3-chlorobenzyl)oxy- and R3 is chloro; (b) R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; (c) R2 is 2-pyridinylmethoxy and R3 is chloro; (d) R2 and R3 are both chloro; (e) R2 is chloro and R3 is bromo; (f) R2 and R3 are both bromo; (g) R2 is fluoro and R3 is ethynyl; (h) R2 is chloro and R3 is ethynyl; (i) R2 is bromo and R3 is ethynyl; (j) other than when R2 is in the 3-position in combination with R3 in the 4-position, R2 is bromo and R3 is fluoro; (k) R2 is 2-pyridinylmethoxy and R3 is fluoro; or (l) R2 is 2-pyridinylmethoxy and R3 is bromo; or (2) at least one of R1, R2 and R3 is selected from benzyloxy, 3-chlorobenzyloxy and 2-pyridinylmethoxy and when at least one of R1, R2 and R3 is not benzyloxy, 3-chlorobenzyloxy or 2-pyridinylmethoxy, each of the others is independently selected from H, halogen, and C2-C4 alkynyl, with the proviso that

Abstract: The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R1 is a group of the formula —(CH2)nTr, where Tr is an aromatic nitroheterocyde or aromatic nitrocarbocycle and —(CH2)nTr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R2, R3 and R4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R2)(R3)(R4)N, or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R2, R3, and R4 may be absent and two of R2, R3 and R4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

Abstract: The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

Abstract: The present invention relates to ketamine derivatives of the formula (I), pharmaceutical compositions comprising them, and methods for treating pain comprising administering them, and their use in the manufacture of medicaments for treating pain. The present invention also relates to methods for anaesthetizing and methods for sedating a subject comprising administering ketamine derivatives of the formula (II).

Abstract: The invention provides kinase inhibitors of Formula I: wherein either: (1) R1 is H, and (a) R2 is (3-chlorobenzyl)oxy-and R3 is chloro; (b) R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; (c) R2 is 2-pyridinylmethoxy and R3 is chloro; (d) R2 and R3 are both chloro; (e) R2 is chloro and R1 is bromo; (f) R2 and R3 are both bromo; (g) R2 is fluoro and R3 is ethynyl; (h) R2 is chloro and R3 is ethynyl; (i) R2 is bromo and R3 is ethynyl; (j) other than when R1 is in the 3-position in combination with R3, in the 4-position, R2 is bromo and R3 is fluoro; (k) R2 is 2-pyridinylmethoxy and R3 is fluoro; or (l) R2 is 2-pyridinylmethoxy and R1 is bromo; or (2) at least one of R1, R2 and R3 is selected from benzyloxy, 3-chlorobenzyloxy and 2-pyridinylmethoxy and when at least one of R1, R2 and R3 is not benzyloxy, 3-chlorobenzyloxy or 2-pyridinylmethoxy, each of the others is independently selected from H, halogen, and C2-C4 alkynyl, with the proviso that

Abstract: Compounds of formula (1a) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, —C1-Cealkyl, —C1-Ceaminoalkyl, —C1-C6hydroxyalkyl, -haloC1-C6alkyl, —C1-C6alkoxyl, -haloC1—C<aIkoxyl, heteroaryl, aryl, hydroxyl, —C(0)Ci-C6alkyl, —OC(0)Ci-C6alkyl, —CH2OC(O)CrC6alkyl, —C(O)OC1, —C6alkyI, —NHC(O)C1, —C6alkyl, —NHS(O)2C1-C6alkyl, —S(O)2C1-C6alkyl, —S(O)2NH2, and —C(O)NJJ; Ring B is a 6-10 membered arylene or a 5-6 membered heteroarylene comprising at least one heteroatom selected from N, 0 or S; and wherein the aryl or heteroaryl is optionally, substituted wit

Abstract: The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R1 is a group of the formula —(CH2)nTr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH2)nTr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R2, R3 and R4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R2)(R3)(R4)N, or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R2, R3 and R4 may be absent and two of R2, R3 and R4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

Abstract: The present invention provides novel compounds of the Formula I, pharmaceutical compositions comprising such compounds and methods for using such compounds as agents or drugs for inhibiting perforin activity and for treating a subject at risk of or susceptible to a disease or disorder, or having a disease or disorder associated with undesirable perforin activity.

Abstract: The current invention pertains to nitroimidazooxazine and nitroimidazooxazole analogues, their methods of preparation, and uses of the compounds as treatment for Mycobacterium tuberculosis, for use as anti-tubercular drugs, for use as anti-protozoal agents with unexpectedly high potency against Trypanosoma cruzi or Leishmania donovani, and for the treatment of other microbial infections.

Abstract: Provided are certain heteroaryl benzamides, compositions, and methods of their manufacture and use.

Abstract: The invention provides kinase inhibitors of Formula I: wherein either: (1) R1 is H, and (a) R2 is (3-chlorobenzyl)oxy- and R3 is chloro; (b) R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; (c) R2 is 2-pyridinylmethoxy and R3 is chloro; (d) R2 and R3 are both chloro; (e) R2 is chloro and R1 is bromo; (f) R2 and R3 are both bromo; (g) R2 is fluoro and R3 is ethynyl; (h) R2 is chloro and R3 is ethynyl; (i) R2 is bromo and R3 is ethynyl; (j) other than when R1 is in the 3-position in combination with R3, in the 4-position, R2 is bromo and R3 is fluoro; (k) R2 is 2-pyridinylmethoxy and R3 is fluoro; or (l) R2 is 2-pyridinylmethoxy and R1 is bromo; or (2) at least one of R1, R2 and R3 is selected from benzyloxy, 3-chlorobenzyloxy and 2-pyridinylmethoxy and when at least one of R1, R2 and R3 is not benzyloxy, 3-chlorobenzyloxy or 2-pyridinylmethoxy, each of the others is independently selected from H, halogen, and C2-C4 alkynyl, with the proviso tha

Abstract: The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R1 is a group of the formula —(CH2)nTr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH2)nTr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R2, R3 and R4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R2)(R3)(R4)N, or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R2, R3 and R4 may be absent and two of R2, R3 and R4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

Abstract: The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

Abstract: The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula I and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.