215790-29-7

Usage

Uses

Used in Pharmaceutical Industry:
TERT-BUTYL TRANS-4-(2-OXOETHYL)CYCLOHEXYLCARBAMATE is used as an intermediate for the synthesis of Cariprazine, a novel antipsychotic medication. Cariprazine acts on dopamine D3/D2 receptors, making it an important treatment option for patients with various psychiatric disorders.
As an intermediate in the synthesis of Cariprazine (C183490), TERT-BUTYL TRANS-4-(2-OXOETHYL)CYCLOHEXYLCARBAMATE plays a vital role in the development of this innovative antipsychotic drug. Its unique chemical properties enable the creation of a medication that can effectively target and modulate dopamine receptors, providing relief for individuals suffering from mental health conditions.

Upstream product

• 22722-98-1 sodium bis(2-methoxyethoxy)aluminium dihydride 
• 1313279-47-8 trans-(4-cyanomethyl-cyclohexyl)-carbamic acid tert-butyl ester 
• 683269-95-6 N-[trans-4-[[(methylsulfonyl)oxy]methyl]cyclohexyl]carbamic acid tert-butyl ester 
• 239074-29-4 trans (4-hydroxymethyl-cyclohexyl)-carbamic acid tert-butyl ester 
• 27960-59-4 trans-4-aminocyclohexanecarboxylic acid hydrochloric acid 
• 146307-51-9 methyl (1R,4R)-4-((tert-butoxycarbonyl)amino)cyclohexane-1-carboxylate 
• 62456-15-9 methyl trans-4-amino-cyclohexanecarboxylate 
• 917342-29-1 trans 2-{1-[4-(N-(tert-butoxycarbonyl))-amino]-cyclohexyl}ethanol 
• 76308-28-6 ethyl 2‐[(1r,4r)‐4‐aminocyclohexyl]acetate 
• 104-03-0 4-nitrobenzeneacetic acid 
• 2952-00-3 trans-2-(4-aminocyclohexyl)acetic acid 
• 946598-34-1 trans 2-{1-[4-(N-(tert-butoxycarbonyl))amino]cyclohexyl}ethyl acetate 
• 76308-27-5 trans-4-aminocyclohexylacetic acid methyl ester 
• 61502-37-2 trans-(4-amino)-cyclohexylacetic acid hydrogen sulfate 

Downstream Products

• 215790-43-5 trans-2-(2-(1-4-(N-tert-butyloxycarbonyl)amino)cyclohexyl)ethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline 
• 264264-44-0 trans-3-(2-(4-(N-tert-butoxycarbonylamino)cyclohexyl)ethyl)-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine 
• 264264-52-0 trans-3-(2-(4-(N-tert-butoxycarbonylamino)cyclohexyl)ethyl)-7-methylsulfonyloxy-2,3,4,5-tetrahydro-1H-3-benzazepine 
• 946598-35-2 trans-(4-{2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-ethyl}-cyclohexyl)-carbamic acid tert-butyl ester 
• 1395922-25-4 trans-{4-[2-(4-benzo[1,3]dioxol-4-yl-piperidin-1-yl)-ethyl]-cyclohexyl}-carbamic acid tert-butyl ester 
• 839712-12-8 Cariprazine 
• 791778-53-5 trans-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexane-1-amine 
• 506427-91-4 trans N-tert-butoxycarbonyl-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethyl}-cyclohexylamine 
• 1356953-51-9 tert-butyl (trans-4-[2-(dimethylamino)ethyl]cyclohexyl)carbamate 

Relevant academic research and scientific papers

C-N bond formation by consecutive continuous-flow reductions towards a medicinally relevant piperazine derivative

A new, continuous-flow consecutive reduction method was developed for the C-N bond formation in the synthesis of the key intermediate of the antipsychotic drug cariprazine. The two-step procedure consists of a DIBAL-H mediated selective ester reduction conducted in a novel, miniature alternating diameter reactor, followed by reductive amination using catalytic hydrogenation on 5% Pt/C. The connection of the optimized modules was accomplished using an at-line extraction to prevent precipitation of the aluminum salt byproducts.

Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor

SB269652 (1) is a negative allosteric modulator of the dopamine D2 receptor. Herein, we present the design, synthesis, and pharmacological evaluation of "second generation" analogues of 1 whereby subtle modifications to the indole-2-carboxamide motif confer dramatic changes in functional affinity (5000-fold increase), cooperativity (100-fold increase), and a novel action to modulate dopamine efficacy. Thus, structural changes to this region of 1 allows the generation of a novel set of analogues with distinct pharmacological properties.

CEREBLON BINDING COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH

Provided herein are piperidine dione compounds having the following structure: wherein R1, R2, R3, R4, L, V, X, A, A′, a and m are as defined herein, compositions comprising an effective amount of a piperidine dione compound, and methods for treating or preventing an androgen receptor mediated disease.

CEREBLON BINDING COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH

Provided herein are piperidine dione compounds having the following structure: wherein RN, R1, R2, R3, R4, RN, L, V, X, a, m, and n are as defined herein, compositions comprising an effective amount of a piperidine dione compound, and methods for treating or preventing an androgen receptor mediated disease.

Preparation method of cariprazine

The invention provides a preparation method of cariprazine, which comprises the following steps: reacting trans-N-tert-butyloxycarbonyl-4-(2-(4-(2,3-dichlorophenyl)-piperazine-1-yl)-ethyl)-cyclohexylamine with dimethylamine under the conditions of an orga

Preparation method of cyclohexane derivative

The invention relates to a preparation method of a cyclohexane derivative. The preparation method comprises the following steps of (1) performing nucleophilic substitution reaction on a compound SM01and a compound SM02 or salts thereof to obtain a compound A; (2) deprotecting the compound A to obtain a compound B; (3) and performing acylation reaction on the compound B and an acylation reagent toobtain the cyclohexane derivative. The disclosed by the method has the advantages of being less in side reaction, high in product yield and purity, and beneficial to industrial scale production.

D2 Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine

Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both Gi/o-bi

INHIBITORS OF THE MENIN-MLL INTERACTION

The present invention is directed to inhibitors of the interaction of menin with MLL and MLL fusion proteins, pharmaceutical compositions containing the same, and their use in the treatment of cancer and other diseases mediated by the menin-MLL interaction.

Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand

Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) (1) adopts a bitopic pose at one protomer of a dopamine D2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxamide moiety of 1 extends into a secondary pocket between the extracellular ends of TM2 and TM7 within the D2R protomer. To target this putative allosteric site, we generated and characterized fragments that include and extend from the 1H-indole-2-carboxamide moiety of 1. N-Isopropyl-1H-indole-2-carboxamide (3) displayed allosteric pharmacology and sensitivity to mutations of the same residues at the top of TM2 as was observed for 1. Using 3 as an "allosteric lead", we designed and synthesized an extensive fragment library to generate novel SAR and identify N-butyl-1H-indole-2-carboxamide (11d), which displayed both increased negative cooperativity and affinity for the D2R. These data illustrate that fragmentation of extended compounds can expose fragments with purely allosteric pharmacology.

Structure-Activity Study of N -((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H -indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D2 Receptor

We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural determinants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric "head" groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R "privileged structures" generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharmacology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R.