186650-79-3

Upstream product

• 67-64-1 acetone 
• 68104-63-2 N-(4-cyanophenyl)piperazine 
• 4318-42-7 1-(1-methylethyl)piperazine 
• 1194-02-1 4-fluorobenzonitrile 

Downstream Products

• 1334717-48-4 7-chloro-2-ethyl-N-[4-(4-isopropylpiperazin-1-yl)benzyl]imidazo[1,2-a]pyridine-3-carboxamide 
• 1018612-68-4 C₁₄H₂₃N₃ 
• 179328-91-7 N,N'-Diethyl-N-[4-(4-isopropyl-piperazin-1-yl)-benzyl]-ethane-1,2-diamine 
• 197638-70-3 N'-Ethyl-N-[4-(4-isopropyl-piperazin-1-yl)-benzyl]-N-methyl-ethane-1,2-diamine 
• 197638-82-7 (2-Chloro-ethyl)-[4-(4-isopropyl-piperazin-1-yl)-benzyl]-methyl-amine 
• 197638-80-5 [4-(4-Isopropyl-piperazin-1-yl)-benzyl]-methyl-amine 
• 197638-78-1 4-(4-isopropylpiperazin-1-yl)benzaldehyde 

Relevant academic research and scientific papers

Identification of N-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents

A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and N-benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides D5, 6, 7, and 12 exhibit excellent in vitro activity against the drug susceptive Mycobacterium tuberculosis H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant strains (MIC 0.016-0.125 μg/mL). Compound D6 displays acceptable safety and better pharmacokinetic profiles than PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.

Lead optimization of a novel series of imidazo[1,2-a]pyridine amides leading to a clinical candidate (Q203) as a multi- and extensively-drug- resistant anti-tuberculosis agent

A critical unmet clinical need to combat the global tuberculosis epidemic is the development of potent agents capable of reducing the time of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper, we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound 1, which led to the design and synthesis of Q203 (50). We found that the amide linker with IPA core is very important for activity against Mycobacterium tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA series play a critical role in improving in vitro and in vivo efficacy and pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the area under curve (AUC) but also displayed significant colony-forming unit (CFU) reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively) in mouse lung.

Synthesis of novel succinamide derivatives having a 5,11-dihydro-6h- pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton as potent and selective M2 muscarinic receptor antagonists. II

A series of succinamide derivatives containing the 5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton (6a-z) was prepared and evaluated for binding affinity to muscarinic receptors in vitro and for antagonism of bradycardia and salivation in vivo in comparison with AF-DX 116 (1a). Structure-activity relationships (SAR) studies in vitro indicated that the 4-(4-alkyl-1-piperazinyl)benzylamino moiety plays a crucial role in enhancing the infinity for M2 muscarinic receptors. Compound 6y, containing a 4-(4-isopropyl-1-piperazinyl)benzylmethylamino moiety, exhibited the highest affinity for M2 muscarinic receptors (pK(i) = 9.2), being 200 times as potent as 1a, and compound 6u, containing a 4-(4-ethyl-1- piperazinyl)benzylethylamino moiety, showed the highest selectivity for M2 over M3 muscarinic receptors (M3/M2 ratio=320). Both 6y and 6u antagonized the oxotremorine-induced bradycardia in rats after intravenous or oral administration. Oral evaluation in conscious dogs showed that the efficacy for increasing the heart rate was at least 3-fold greater than that of 1a.