50606-32-1

Usage

Uses

Used in Pharmaceutical Industry:
N-(n-butoxycarbonyl)piperazine is used as a building block for the synthesis of various pharmaceutical compounds. The Boc group allows for specific reactions to occur at the unprotected sites of the piperazine molecule, facilitating the development of novel drug candidates.
Used in Agrochemical Industry:
N-(n-butoxycarbonyl)piperazine is used as a building block for the synthesis of various agrochemical compounds. Its versatility and the protective Boc group enable the development of new agrochemical products.
Used in Organic Synthesis:
N-(n-butoxycarbonyl)piperazine is used as a reagent in organic synthesis. The Boc group allows for specific reactions to occur, making it a valuable component in the preparation of peptide and organic compounds.
Used in Manufacturing of Pharmaceutical Products:
N-(n-butoxycarbonyl)piperazine is used as a precursor in the manufacturing of pharmaceutical products. Its role in the synthesis of various compounds makes it an important component in the development and production of pharmaceuticals.

Upstream product

• 110-85-0 piperazine 
• 592-34-7 carbonochloridic acid, butyl ester 
• 1073554-07-0 piperazine-1,4-dicarboxylic acid tert-butyl ester butyl ester 
• 1019928-96-1 4-benzylpiperazine-1-carboxylic acid butyl ester 

Downstream Products

• 1159502-62-1 4-[2-benzyloxycarbonylamino-2-(dimethoxy-phosphoryl)-acetyl]-piperazine-1-carboxylic acid butyl ester 
• 1019929-05-5 butyl (S)-4-(2-benzyloxycarbonylamino-4-tert-butoxycarbonylbutyryl)piperazine-1-carboxylate 
• 1021703-38-7 4-{(S)-4-tert-butoxycarbonyl-2-[(6-chloro-2-phenyl-pyrimidine-4-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid butyl ester 
• 1190713-25-7 3.3. 4-((S)-4-tert-butoxycarbonyl-2-{[6-((1S,2S)-2-methoxymethyl-cyclopropyl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid butyl ester 
• 1190713-15-5 4-((S)-4-carboxy-2-{[6-((1S,2S)-2-methoxymethylcyclopropyl)-2-phenylpyrimidine-4-carbonyl]amino}butyryl)piperazine-1-carboxylic acid butyl ester 

Relevant academic research and scientific papers

4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y12 Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel

Recent post hoc analyses of several clinical trials with P2Y12 antagonists showed the need for new molecules being fully efficacious as antiplatelet agents and having a reduced propensity to cause major bleeding. We have previously reported the discovery of the 2-phenylpyrimidine-4-carboxamide analogs as P2Y12 antagonists with nanomolar potency in the disease-relevant platelet aggregation assay in human plasma. Herein we present the optimization steps that led to the discovery of clinical candidate ACT-246475 (30d). The key step was the replacement of the carboxylic acid functionality by a phosphonic acid group which delivered the most potent molecules of the program. In addition, low in vivo clearance in rat and dog was achieved for the first time. Since the bioavailability of 30d was low in rat and dog, we developed the bis((isopropoxycarbonyl)oxy)methyl ester prodrug (ACT-281959, 45). Compound 30d showed efficacy in the rat ferric chloride thrombosis model when administered intravenously as parent or orally as its prodrug 45. Moreover, 30d displays a wider therapeutic window as compared to clopidogrel in the rat surgical blood loss model.

Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable and selective P2Y12 antagonists for inhibition of platelet aggregation

2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y 12 antagonists. Optimization of the carbon-linked or nitrogen-linked substituent at the 6-position of the pyrimidine ring provided compounds with excellent ex vivo potency in the

Piperazinyl glutamate pyridines as potent orally bioavailable P2Y 12 antagonists for inhibition of platelet aggregation

Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl glutamate pyridine as a P2Y12 antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized through modifications at the 4-position of the pyridine ring and the terminal nitrogen of the piperazine ring, leading to compound (4S)-4-[({4-[4-(methoxymethyl) piperidin-1-yl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy) carbonyl]piperazin-1-yl}pentanoic acid 47s with good human PRP potency, selectivity, in vivo efficacy, and oral bioavailability. Compound 47s was selected for further preclinical evaluations.

2-PHENYL-6-AMINOCARBONYL-PYRIMIDINE DERIVATIVES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS

The invention relates to 2-phenyl-6-aminocarbonyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention and/or treatment of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. Formula (I).

6-(3-AZA-BICYCLO[3.1.0]HEX-3-YL)-2-PHENYL-PYRIMIDINES

The present invention relates to 6-(3-aza-bicyclo[3.1.0]hex-3-yl)-2-phenyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.

PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS

The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

2-PHENYL-6-AMINOCARBONYL-PYRIMIDINE DERIVATIVES AND THEIR USE AS P2Y12 RECEPTOR

The invention relates to 2-phenyl-6-aminbcarbonyl-pyrimidinc derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention and/or treatment of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. Formula (1).

2-AMINOCARBONYL-PYRIDINE DERIVATIVES

The present invention relates to 2-aminocarbonyl-pyridine derivatives and their use as P2Yi2 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.