131645-73-3

Upstream product

• 603-11-2 3-nitrophthalic acid 
• 641-70-3 3-nitrophthalic acid anhydride 
• 77326-45-5 2-carbamoyl-3-nitrobenzoic acid 
• 606-18-8 3-nitroanthranilic acid 

Downstream Products

• 162930-60-1 2-amino-3-nitro-N-(2-oxopentyl)benzamide 
• 162930-59-8 2-amino-N-(3-methyl-2-oxobutyl)-3-nitrobenzamide 
• 162930-61-2 N-(2-amino-3-nitrobenzoyl)benzeneacetamide 
• 313279-12-8 2-amino-3-nitro-benzamide 
• 711007-44-2 2,3-diaminobenzamide 
• 313279-21-9 2-(3-hydroxymethyl-phenyl)-1H-benzoimidazole-4-carboxylic acid amide 
• 313279-20-8 2-[4-(hydroxymethyl)phenyl]-1H-benzimidazole-4-carboxamide 
• 313279-17-3 2-(4-triisopropylsilanyloxymethyl-phenyl)-1H-benzoimidazole-4-carboxylic acid amide 
• 313279-18-4 2-(3-triisopropylsilanyloxymethyl-phenyl)-1H-benzoimidazole-4-carboxylic acid amide 
• 313279-19-5 2-(2-triisopropylsilanyloxymethyl-phenyl)-1H-benzoimidazole-4-carboxylic acid amide 
• 1025839-42-2 2-Phenyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-9-ylamine 
• 162930-64-5 9-amino-3,4-dihydro-2-phenyl-5H-1,4-benzodiazepin-5-one 
• 131645-74-4 ethyl N-(2-amino-3-nitrobenzoyl)-N-propylalanine 
• 272769-49-0 2-(1-propyl-4-piperidinyl)-1H-benzimidazole-4-carboxamide 

Relevant academic research and scientific papers

Process development for ABT-472, a benzimidazole PARP inhibitor

A nine-step convergent process was developed for the synthesis of ABT-472, a benzimidazole PARP inhibitor. The identity and origin of several impurities were determined, and the process was modified to reduce or eliminate these impurities. A number of safety and control issues were investigated. The original synthesis was shortened to 9 steps and streamlined while maintaining a convergent strategy. A stable salt was selected, and control of the API solid form was established. The process was successfully scaled up to provide 8.5 kg of final product of >99% purity in 33% yield over 9 steps.

Synthesis and evaluation of 2-(4-[4-acetylpiperazine-1-carbonyl] phenyl)-1H-benzo[d]imidazole-4-carboxamide derivatives as potential PARP-1 inhibitors and preliminary study on structure-activity relationship

Although 1H-benzo[d]imidazole-4-carboxamide derivatives have been explored for a long time, the structure–activity relationship of the substituents in the hydrophobic pocket (AD binding sites) has not thoroughly discovered. Here in, a series of 2-(4-[4-acetylpiperazine-1-carbonyl]phenyl)-1H-benzo[d]imidazole-4-carboxamide derivatives have been designed, synthesized, and successful characterization as novel and effective poly ADP-ribose polymerases (PARP)-1 inhibitors to improve the structure–activity relationships about the substituents in the hydrophobic pocket. These derivatives were evaluated for their PARP-1 inhibitory activity and cellular inhibitory against BRCA-1 deficient cells (MDA-MB-436) and wild cells (MCF-7) using PARP kit assay and MTT method. The results indicated that compared with other heterocyclic compounds, furan ring-substituted derivatives 14n-14q showed better PARP-1 inhibitory activity. Among this derivatives, compound 14p displayed the strongest inhibitory effects on PARP-1 enzyme (IC50?=?0.023 μM), which was close to that of Olaparib. 14p (IC50?=?43.56 ± 0.69 μM) and 14q (IC50?=?36.69 ± 0.83 μM) displayed good antiproliferation activity on MDA-MB-436 cells and inactivity on MCF-7 cells, indicating that 14p and 14q have high selectivity and targeting. The molecular docking method was used to explore the binding mode of compound 14p and PARP-1, and implied that the formation of hydrogen bond was essential for PARP-1 inhibition activities. This study also showed that in the hydrophobic pocket (AD binding sites), the introduction of strong electronegative groups (furan ring, e.g.) or halogen atoms in the side chain of benzimidazole might improve its inhibitory activity and this strategy could be applied in further research.

Discovery of novel 1,5-benzodiazepine-2,4-dione derivatives as potential anticancer agents

A series of novel 1,5-benzodiazepine-2,4-dione derivatives with C-6 amide substituents were designed and synthesized using three-component reactions. The preliminary assays showed that most of them displayed moderate to good antitumor activities against human lung carcinoma (A549), human breast epithelial carcinoma (MCF-7), human colon carcinoma (HCT116), human cervical carcinoma (Hela) and Lewis lung carcinoma (2LL). Exhilaratingly, the activity level of 6m rivaled that of 5-Fluorouracil (5-Fu) against MCF-7 cell lines, which might be used as novel lead scaffold for potential anticancer development.

Fluoroalkyl-substituted 2-amidobenzimidazoles

Use of fluoroalkyl-substituted 2-amidobenzimidazoles of the formula (I), or salts thereof, for enhancing stress tolerance in plants to abiotic stress, especially for strengthening plant growth and/or for increasing plant yield, and selected processes for preparing such fluoroalkyl-substituted 2-amidobenzimidazoles of the formula (I).

SUBSTITUTED 1H-BENZIMIDAZOLE-4-CARBOXAMIDES ARE POTENT PARP INHIBITORS

Compounds of Formula (I) inhibit the PARP enzyme and are useful for treating a disease or a disorder associated with PARP. Also disclosed are pharmaceutical compositions comprising compounds of Formula (I), methods of treatment comprising compounds of For

NEW ALICYCLIC-AMINE-SUBSTITUTED 4-CARBOXAMIDO-BENZIMIDAZOLES AS PARP-INHIBITORS AND ANTIOXIDANTS

Compounds of the formula (I) and their pharmaceutically acceptable or technically applicable acid salts - where in the formula R1 represents hydrogen, C(1-4) alkyl or C(1-4) alkoxy R2 represents hydrogen, C(1-4) alkyl, carboxyl, C(1-4) alkoxycarbonyl, carboxamido,aryl or hetero-aryl R3 represents hydrogen, C(1-4) alkyl, aryl-methylene, or aryl, Y is a valency bond, a straight or branched chain C(1-4) alkene, a carbonyl-amino- C(1-4) alkene, or a -S- (CH2)m- group, where all alkene groups above may be spaced by an arylene group, n represents zero or the integer 1 m represents the integer 1, 2 or 3 Q represents hydrogen, hydroxyl or the oxygen radical (0) or together with the N atom of the adjacent ring forms a +N=O (oxoimmonium) group Z represents a single or double bond and their pharmaceutically acceptable or technically useful salts, processes for their preparation and their biological use as PARP inhibitors and antioxidants.

Resistance-modifying agents. 9. Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase

The nuclear enzyme poly(ADP-ribose) polymerase (PARP) facilitates the repair of DNA strand breaks and is implicated in the resistance of cancer cells to certain DNA-damaging agents. Inhibitors of PARP have clinical potential as resistance-modifying agents capable of potentiating radiotherapy and the cytotoxicity of some forms of cancer chemotherapy. The preclinical development of 2-aryl-1H-benzimidazole-4-carboxamides as resistance-modifying agents in cancer chemotherapy is described. 1H-Benzimidazole-4-carboxamides, particularly 2-aryl derivatives, are identified as a class of potent PARP inhibitors. Derivatives of 2-phenyl-1H-benzimidazole-4-carboxamide (23, K(i) = 15 nM), in which the phenyl ring contains substituents, have been synthesized. Many of these derivatives exhibit K(i) values for PARP inhibition 10 nM, with 2-(4-hydroxymethylphenyl)-1H-benzimidazole-4-carboxamide (78, K(i) = 1.6 nM) being one of the most potent. Insight into structure-activity relationships (SAR) for 2-aryl-1H-benzimidazole-4-carboxamides has been enhanced by studying the complex formed between 2-(3-methoxyphenyl)-1H-benzimidazole-4-carboxamide (44, K(i) = 6 nM) and the catalytic domain of chicken PARP. Important hydrogen-bonding and hydrophobic interactions with the protein have been identified for this inhibitor. 2-(4-Hydroxyphenyl)-1H-benzimidazole-4-carboxamide (45, K(i) = 6 nM) potentiates the cytotoxicity of both temozolomide and topotecan against A2780 cells in vitro (by 2.8- and 2.9-fold, respectively).

Synthesis anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1- jk][1,4]benzodiazepin-2(1H)-one (TIBO) derivatives. 3

4,5,6,7-Tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones (TIBO), 1, have been shown to significantly inhibit HIV-1 replication in vitro by interfering with the virus's reverse transcriptase enzyme. They have also demonstrated potential cl

Anti-HIV-1 tetrahydroimidazo[1,4]benzodiazepin-2-(thi) ones

Novel tetrahydroimidazo[1,4]benzodiazepin-2-(thi)ones possessing anti-HIV-1 activity, compositions containing these compounds as active ingredients, and methods of treating subjects suffering from HIV-1 infection by administering these compounds. The comp