The disclosure relates to compounds of formula (I), which are formyl peptide 2 (FPR2) receptor agonists and/or formyl peptide 1 (FPR1) receptor agonists. The disclosure also provides compositions and methods of using the compounds, for example, for the treatment of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases. ##STR00001##

The present disclosure reports an extensive medicinal chemistry evaluation of a large collection of Truncating APC-Selective Inhibitor (TASIN) compounds. The compounds were evaluated for activity against a series of colon cancer cell lines with and without truncating APC-mutations, as well as in an isogenic cell line pair reporting on the status of APC-dependent selectivity. A number of very potent and selective compounds were identified, including compounds with good metabolic stability and PK properties. The small molecules reported herein thus represent a first-in-class genotype-selective series that specifically target ape mutations present in the vast majority of CRC patients, and therefore serves as a translational platform towards a potential targeted therapy for colon cancer.

The present disclosure reports an extensive medicinal chemistry evaluation of a large collection of Truncating APC-Selective Inhibitor (TASIN) compounds. The compounds were evaluated for activity against a series of colon cancer cell lines with and without truncating APC-mutations, as well as in an isogenic cell line pair reporting on the status of APC-dependent selectivity. A number of very potent and selective compounds were identified, including compounds with good metabolic stability and PK properties. The small molecules reported herein thus represent a first-in-class genotype-selective series that specifically target ape mutations present in the vast majority of CRC patients, and therefore serves as a translational platform towards a potential targeted therapy for colon cancer.

Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is —OR.sub.i or —NR.sub.2aR.sub.2b; R.sub.3 is hydrogen or substituted or unsubstituted heteroalicyclyl, R.sub.4 is substituted or unsubstituted aralkyl; X is —OR.sub.22 or —NR.sub.23R.sub.24; (wherein R.sub.22 is hydrogen or substituted or unsubstituted C.sub.1-6alkyl and one of R.sub.23 and R.sub.24 is hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and R.sub.21 is —OCH.sub.2CH(CH.sub.3).sub.2 or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt.

##STR00001##

Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is —OR.sub.i or —NR.sub.2aR.sub.2b; R.sub.3 is hydrogen or substituted or unsubstituted heteroalicyclyl, R.sub.4 is substituted or unsubstituted aralkyl; X is —OR.sub.22 or —NR.sub.23R.sub.24; (wherein R.sub.22 is hydrogen or substituted or unsubstituted C.sub.1-6alkyl and one of R.sub.23 and R.sub.24 is hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and R.sub.21 is —OCH.sub.2CH(CH.sub.3).sub.2 or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt.

##STR00001##

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 present disclosure relates generally to therapeutic agents that may be useful as inhibitors of Integrated Stress Response (ISR) pathway.

The invention relates to glutarimide compounds of formula I, (I) wherein the variables have the meanings as defined in the specification, to compositions comprising them, to active compound combinations comprising them, and to their use for protecting growing plants and animals from attack or infestation by invertebrate pests, furthermore, to seed comprising such compounds.

##STR00001##

The invention relates to glutarimide compounds of formula I, (I) wherein the variables have the meanings as defined in the specification, to compositions comprising them, to active compound combinations comprising them, and to their use for protecting growing plants and animals from attack or infestation by invertebrate pests, furthermore, to seed comprising such compounds.

##STR00001##