Abstract: The invention relates to 2-methylbenzoxazole compounds of formula I which are analogues of the DNA alkylating subunit of the duocarmycins. Compounds of formula I can be used in the synthesis of DNA alkylating agents and antibody-drug conjugates and related compounds. The 2-methylbenzoxaxole unit of formula I has advantageous properties in combining high cytotoxicity, low lipophilicity, and unusual aqueous stability, all of which are desirable for application as payloads in efficacious antibody-drug conjugates.

Abstract: This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Abstract: This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Abstract: This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

Abstract: This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

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 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: 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 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 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.

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.

Abstract: This invention relates to pyrrolocarbazole derivatives according formula I wherein R1, R2, R7, R8, R9, X and Y are as defined in the specification wherein said derivatives specifically inhibit one or both of the checkpoint kinases Wee1 and Chk1

Abstract: The present invention provides novel 5-substituted tetralones of Formulas I, II, III, and IV and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, which are useful for treating and preventing uncontrolled or abnormal proliferation of tissues, such as cancer, atherosclerosis, restenosis, and psoriasis.

Abstract: The present invention provides novel 5-substituted tetralones of Formulas (I), (II), (III) and (IV) and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, which are useful for treating and preventing uncontrolled or abnormal proliferation of tissues, such as cancer, atherosclerosis, restenosis, and psoriasis. Specifically, the present invention relates to compounds that inhibit the farnesyl transferase enzyme.

Abstract: A process for the preparation of the compound AQ4 of formula 3: or a salt or N-oxide thereof, includes the step: