The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

The invention relates to a compound of formula (I)

##STR00001##

wherein A.sup.1, A.sup.2 and R.sup.1 to R.sup.3 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

The invention relates to a compound of formula (I)

##STR00001##

wherein A.sup.1, A.sup.2 and R.sup.1 to R.sup.3 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

The combination of 3-phenylsulfonyl-8-piperazinyl-1yl-quinoline or a pharmaceutically acceptable salt thereof with a second therapeutic agent, wherein the second therapeutic agent is selected from: (a) a therapeutic agent known to modify cholinergic transmission such as M1 muscarinic receptor agonists or allosteric modulators, M2 muscarinic antagonists, acetylcholinesterase inhibitors, nicotinic receptor agonists or allosteric modulators, 5-HT4 receptor partial agonists or 5HT1A receptor antagonists and NMDA receptor antagonists or modulators, glutamate antagonists, GABA-ergic antagonists, H3 antagonists, putative metabolic/mitochondrial modulators, or disease modifying agents such as β or γ-secretase inhibitors, Tau-targeted therapeutics, β-amyloid aggregation inhibitors and β-amyloid immunotherapies; (b) an antidepressant such as a tricyclic, a MAOI (Monoamine oxidase inhibitor) a SSRI (Selective Serotonin Reuptake Inhibitor), a SNRI (Serotonin and Noradrenaline Reuptake Inhibitor) or a NaSSA (noradrenergeric and specific serotonergic antidepressant); (c) an atypical antipsychotic, for example olanzapine, clozapine, prisperidone, quentiapine, aripriprazole or paliperiden; or (d) a therapeutic agent suitable for use in Attention Deficit Disorders/Hyperactivity Syndrome, e.g. methylphenidate (Ritalin) or dexamfetamine (Dexedrine), and also the use of 3-phenylsulfonyl-8-piperazinyl-1yl-quinoline or a pharmaceutically acceptable salt thereof for the treatment of: a) psychiatric disorders with prominent cognitive deficits e.g. chronic PTSD (Post traumatic stress disorder); b) non-degenerative disorders with prominent cognitive deficits e.g. MS (multiple Sclerosis), post-chemotherapy, post-CABG (Coronary artery bypass graft), post-stroke; and/or c) paediatric disorders e.g. autism, mental retardation and learning disabilities.

The present invention relates to combination therapies for treating KRas G12C cancers. In particular, the present invention relates to methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a mTOR inhibitor and a KRAS G12C inhibitor of Formula (I), Formula I-A or Formula I-B, pharmaceutical compositions comprising a therapeutically effective amounts of the inhibitors, kits comprising the compositions and methods of use therefor.

The present invention relates to combination therapies for treating KRas G12C cancers. In particular, the present invention relates to methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a mTOR inhibitor and a KRAS G12C inhibitor of Formula (I), Formula I-A or Formula I-B, pharmaceutical compositions comprising a therapeutically effective amounts of the inhibitors, kits comprising the compositions and methods of use therefor.

Methods of treating or preventing cancer, or treating or preventing noncancerous tumors or lesions, in a subject in need thereof. The methods involve administering a therapeutically effective amount of one or more inhibitors of the YAP/TAZ pathway to the subject. In addition, methods of inhibiting or preventing glycolysis in cancer cells in a subject, promoting mitochondrial respiration in cancer cells in a subject, and promoting oxidative stress in cancer cells in a subject, by administering a therapeutically effective amount of one or more inhibitors of the YAP/TAZ pathway to the subject.

Methods of treating or preventing cancer, or treating or preventing noncancerous tumors or lesions, in a subject in need thereof. The methods involve administering a therapeutically effective amount of one or more inhibitors of the YAP/TAZ pathway to the subject. In addition, methods of inhibiting or preventing glycolysis in cancer cells in a subject, promoting mitochondrial respiration in cancer cells in a subject, and promoting oxidative stress in cancer cells in a subject, by administering a therapeutically effective amount of one or more inhibitors of the YAP/TAZ pathway to the subject.

Disclosed are small molecules against cereblon to enhance effector T cell function. Methods of making these molecules and methods of using them to treat various disease states are also disclosed.