Patent classifications
A61K31/553
CERTAIN (2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE 1 INHIBITORS
The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof),
##STR00001##
that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
HIV INHIBITOR COMPOUNDS
The invention provides a compound of Formula I:
##STR00001##
or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I.
HIV INHIBITOR COMPOUNDS
The invention provides a compound of Formula I:
##STR00001##
or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I.
METHODS OF USE FOR PYRIMIDINES AS FERROPORTIN INHIBITORS
The subject matter described herein is directed to ferroportin inhibitor compounds of Formula (I) and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of administering the compounds for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis, and also kidney injuries.
METHODS OF USE FOR PYRIMIDINES AS FERROPORTIN INHIBITORS
The subject matter described herein is directed to ferroportin inhibitor compounds of Formula (I) and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of administering the compounds for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis, and also kidney injuries.
HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS
The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.
HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS
The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.
BENZOLACTAM COMPOUNDS AS PROTEIN KINASE INHIBITORS
- Valerio Berdini ,
- Ildiko Maria Buck ,
- James Edward Harvey Day ,
- Charlotte Mary Griffiths-Jones ,
- Thomas Daniel Heightman ,
- Steven Howard ,
- Christopher William Murray ,
- David Norton ,
- Marc O'Reilly ,
- Alison Jo-Anne Woolford ,
- Michael Liam Cooke ,
- David Cousin ,
- Stuart Thomas Onions ,
- Jonathan Martin Shannon ,
- John Paul Watts
The invention provides a compound of formula (0):
##STR00001## or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—R.sup.z and N; R.sup.1 is selected from: -(Alk.sup.1).sub.t-Cyc.sup.1; wherein t is 0 or 1; Optionally substituted C.sub.1-6 acyclic hydrocarbon groups R.sup.2 is selected from hydrogen; halogen; and C.sub.1-3 hydrocarbon groups optionally substituted with one or more fluorine atoms; R.sup.3 is hydrogen or a group L.sup.1-R.sup.7; R.sup.4 is selected from hydrogen; methoxy; and optionally substituted C.sub.1-3 alkyl; and R.sup.4a is selected from hydrogen and a C.sub.1-3 alkyl group; wherein R.sup.z, Alk.sup.1, Cyc.sup.1, L.sup.1 and R.sup.7 are defined herein; provided that the compound is other than 6-benzyl-3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof.
The compounds are inhibitors of ERK1/2 kinases and will be useful in the treatment of ERK1/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.
BENZOLACTAM COMPOUNDS AS PROTEIN KINASE INHIBITORS
- Valerio Berdini ,
- Ildiko Maria Buck ,
- James Edward Harvey Day ,
- Charlotte Mary Griffiths-Jones ,
- Thomas Daniel Heightman ,
- Steven Howard ,
- Christopher William Murray ,
- David Norton ,
- Marc O'Reilly ,
- Alison Jo-Anne Woolford ,
- Michael Liam Cooke ,
- David Cousin ,
- Stuart Thomas Onions ,
- Jonathan Martin Shannon ,
- John Paul Watts
The invention provides a compound of formula (0):
##STR00001## or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—R.sup.z and N; R.sup.1 is selected from: -(Alk.sup.1).sub.t-Cyc.sup.1; wherein t is 0 or 1; Optionally substituted C.sub.1-6 acyclic hydrocarbon groups R.sup.2 is selected from hydrogen; halogen; and C.sub.1-3 hydrocarbon groups optionally substituted with one or more fluorine atoms; R.sup.3 is hydrogen or a group L.sup.1-R.sup.7; R.sup.4 is selected from hydrogen; methoxy; and optionally substituted C.sub.1-3 alkyl; and R.sup.4a is selected from hydrogen and a C.sub.1-3 alkyl group; wherein R.sup.z, Alk.sup.1, Cyc.sup.1, L.sup.1 and R.sup.7 are defined herein; provided that the compound is other than 6-benzyl-3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof.
The compounds are inhibitors of ERK1/2 kinases and will be useful in the treatment of ERK1/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.
COMBINATION MCL-1 INHIBITORS WITH ANTI-CANCER AGENTS
The present disclosure generally relates to methods of treating cancer by administering an MCL-1 inhibitor and an anticancer agent.