81156-65-2

Upstream product

• 35364-79-5 2-(3,4-dichlorophenyl)ethanol 
• 5807-30-7 3,4-dichlorophenyl acetic acid 
• 124-63-0 methanesulfonyl chloride 
• 6725-45-7 ethyl 3,4-dichlorophenylacetate 

Downstream Products

• 1192365-94-8 N'-(3,4-dichlorophenethyl)-3-(4-(methylsulfonamido)phenyl)propanehydrazide 
• 1197396-96-5 2-[(4-{[2-(3,4-dichlorophenyl)ethyl]amino}-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione 
• 114686-64-5 1-iodo-2-(3,4-dichlorophenyl)ethane 
• 119745-52-7 [(S)-1-{(R)-1-[({[2-(3,4-Dichloro-phenyl)-ethyl]-ethyl-carbamoyl}-methyl)-carbamoyl]-4-guanidino-butylcarbamoyl}-2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 119744-95-5 ({[2-(3,4-Dichloro-phenyl)-ethyl]-ethyl-carbamoyl}-methyl)-carbamic acid tert-butyl ester 
• 130553-86-5 BD 614 

Relevant academic research and scientific papers

NURR1 RECEPTOR MODULATORS

Described herein, inter alia, are Nurr1 receptor modulators and uses thereof. In an aspect is provided a method for treating a disease associated with dysregulation and/or degeneration of dopaminergic neurons in the central nervous system of a subject in need thereof, the method including administering to the subject in need thereof a therapeutically effective amount of a compound described herein.

HETEROARYL RHEB INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same. Compositions comprising a compound of this invention or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of the compound in compositions of this invention is such that it is effective to measurably inhibit Rheb, in a biological sample or in a patient.

BICYCLIC HETEROCYCLE DERIVATIVES AS BROMODOMAIN INHIBITORS

The invention relates to novel bicyclic heterocycle derivatives of formula (I) wherein Cy1,Cy2, R1,R2 and L have the meaning given in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula (I) are usefulas bromodomain inhibitors in the treatment or prevention of diseases or disorders where bromodomain inhibition is desired.

Synthesis, structural activity-relationships, and biological evaluation of novel amide-based allosteric binding site antagonists in NR1A/NR2B N-methyl-d-aspartate receptors

The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the hERG channel and α1-adrenergic receptors. Selections of the compounds discussed have acceptable half-lives in vivo and are predicted to permeate the blood-brain barrier. These data together suggest that masking charged atoms on the linker region of NR2B-selective antagonists can decrease undesirable side effects while still maintaining on-target potency.

TRICYCLIC NITROGEN CONTAINING COMPOUNDS AND THEIR USE AS ANTIBACTERIALS

Compounds of Formula (I) or a pharmaceutically acceptable salt or N-oxide thereof; Formula (I) (relative stereochemistry shown) wherein: Z1, Z2 , L are as defined, U represents a cyclic group selected from: phenyl, pyridyl, pyridazin

Synthesis and evaluation of N-substituted cis-N-methyl-2-(1-pyrrolidinyl)cyclohexylamines as high affinity σ receptor ligands. Identification of a new class of highly potent and selective σ receptor probes

Certain benzeneacetamides [(-)- and (+)-cis-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzenea cetamide] were recently reported to be potent σ receptor ligands. In order to determine whether efficacy for the σ receptor could be improved, a series of compounds related to the benzeneacetamides, N-substituted cis-2-(1-pyrrolidinyl)-N-methylcyclohexylamines, were synthesized and their structure-activity requirements were determined. The compounds were synthesized by starting with the previously reported (±)-, 1S,2R-(+)-, and 1R,2S-(-)-cis-2-(1-pyrrolidinyl)-N-methylcyclohexylamines. Analysis of σ ([3H](+)-3-PPP), κ ([3H]bremazocine and [3H]U69,593), dopamine-d2 ([3H](-)-sulpiride), and phencyclidine (PCP) ([3H]TCP) receptor binding in guinea pig brain revealed a number of highly potent and selective σ receptor ligands. Notably, 1S,2R-cis-(-)-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-(2-naphthyl)ac etamide [(-)-29] (K(i) = 8.66 ± 0.35 nM), (±)-cis-2-amino-4,5-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl ]benzeneacetamide [(±)-17] (K(i) = 11 ± 3 nM), 1S,2R-(-)-cis-N-methyl-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidin yl)cyclohexylamine [(-)-44] (K(i) = 1.3 ± 0.3 nM), and 1R,2S-(+)-cis-N-methyl-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidin yl)cyclohexylamine. [(+)-44] (K(i) = 6 ± 3 nM) exhibited very high affinity at σ receptors, by displacement of [3H]-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([3H]-(+)-3-PPP). These compounds showed significant affinity for κ, dopamine, or PCP receptors, making them valuable tools for the study of σ receptors. Furthermore, these compounds also exhibited enantioselectivity ranging from 5-fold for (+)- and (-)-44 to 160-fold for (+)- and (-)-29. Several other compounds showed equivalent selectivity but displayed lower σ receptor affinity.

Peripherally Acting Enkephalin Analogues. 2. Polar Tri- and Tetrapeptides

The design, synthesis, and biological activity of a series of -Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported.These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors.The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity.The peptides were all synthesized by classical solution methodology.The opioid activit y of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents.That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests.As a class, the tetrapeptides were more potent than the tripeptides; Nα-amidination generally increased activity.A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.

Benzothiazepine vasodilators having aralkyl substitution

N-Aminoalkyl 1,5-benzothiazepines of the following formula (I): STR1 for the treatment of angina or hypertension or the prevention of heart attacks in mammals, in particular their use as coronary vasodilators.