The present invention relates to a compound used as an RET kinase inhibitor and an application thereof. The compound has a structure represented by formula F, has a good inhibitory ability for RET kinase, and has relatively good pharmacodynamic and pharmacokinetic performance, and lower toxic side effects.

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The present invention relates to a compound used as an RET kinase inhibitor and an application thereof. The compound has a structure represented by formula F, has a good inhibitory ability for RET kinase, and has relatively good pharmacodynamic and pharmacokinetic performance, and lower toxic side effects.

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The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof),

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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.

The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof),

##STR(I)##

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.

The present invention is directed to a method of treatment, including prevention or reducing the likelihood of adverse effects of chemotherapy comprising reducing and/or inhibiting chemotherapy-induced adverse effects (CIAE), especially central nervous system adverse effects, such as cognitive effects (especially chemotherapy induced cognitive impairment or CICI, also referred to as reduced cognition, cognitive impairment or chemobrain) by administering to the patient in need, including co-administering to the subject in need a pharmaceutically effective amount of a protein kinase C (PKC, often, PKC α and/or β) inhibitor, alone or in combination with a lithium salt. Related pharmaceutical compositions are also provided by the present invention.

The present invention is directed to a method of treatment, including prevention or reducing the likelihood of adverse effects of chemotherapy comprising reducing and/or inhibiting chemotherapy-induced adverse effects (CIAE), especially central nervous system adverse effects, such as cognitive effects (especially chemotherapy induced cognitive impairment or CICI, also referred to as reduced cognition, cognitive impairment or chemobrain) by administering to the patient in need, including co-administering to the subject in need a pharmaceutically effective amount of a protein kinase C (PKC, often, PKC α and/or β) inhibitor, alone or in combination with a lithium salt. Related pharmaceutical compositions are also provided by the present invention.

Combinations of a voltage-gated sodium channel (VGSC) blocker and at least one other substance that directly or indirectly modulate ionic mechanisms, e.g., a potassium channel opener, sodium influx inhibitor or upstream down-regulator of VGSC expression, for treating or preventing cancer, including reducing, preventing or inhibiting metastatic and/or invasive behaviour of the cancer.

Combinations of a voltage-gated sodium channel (VGSC) blocker and at least one other substance that directly or indirectly modulate ionic mechanisms, e.g., a potassium channel opener, sodium influx inhibitor or upstream down-regulator of VGSC expression, for treating or preventing cancer, including reducing, preventing or inhibiting metastatic and/or invasive behaviour of the cancer.

Combinations of a voltage-gated sodium channel (VGSC) blocker and at least one other substance that directly or indirectly modulate ionic mechanisms, e.g., a potassium channel opener, sodium influx inhibitor or upstream down-regulator of VGSC expression, for treating or preventing cancer, including reducing, preventing or inhibiting metastatic and/or invasive behaviour of the cancer.

Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I):

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including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, X, Y.sup.1, Y.sup.2, or L are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.