1332634-91-9

Upstream product

• 23008-56-2 N-(4-chlorophenyl)-2-nitroaniline 
• 1493-27-2 ortho-nitrofluorobenzene 
• 327-92-4 1,5-difluoro-2,4-dinitrobenzene 
• 68817-71-0 2-(4-chloroanilino)aniline 

Downstream Products

• 1353740-42-7 N¹-(4-chlorophenyl)-N²-[2,4-dinitro-5-(pyridin-3-ylamino)phenyl]benzene-1,2-diamine 
• 1353740-44-9 5-(4-chlorophenyl)-3-imino-N-(pyridin-3-yl)-3,5-dihydrophenazin-2-amine 
• 1353730-91-2 5-(4-chlorophenyl)-3-isopropylimino-2-(3-pyridylamino)-3,5-dihydrophenazine 
• 1353737-67-3 5-(4-chlorophenyl)-3-(4-methoxycyclohexyl)imino-2-(3-pyridyl)amino-3,5-dihydrophenazine 
• 1353737-62-8 5-(4-chlorophenyl)-3-(4-tetrahydropyranyl)imino-2-(3-pyridyl)amino-3,5-dihydrophenazine 
• 1401207-31-5 5-(4-chlorophenyl)-3-(4-methoxycyclohexyl)imino-2-(5-bromo-3-pyridyl)amino-3,5-dihydrophenazine 
• 1353736-14-7 5-(4-chlorophenyl)-3-(4-tetrahydropyranyl)imino-2-(5-bromo-3-pyridyl)amino-3,5-dihydrophenazine 
• 1353737-93-5 5-(4-chlorophenyl)-3-(4-methoxycyclohexyl)imino-2-(6-methyl-3-pyridyl)amino-3,5-dihydrophenazine 
• 1353737-91-3 5-(4-chlorophenyl)-3-(4-tetrahydropyranyl)imino-2-(6-methyl-3-pyridyl)amino-3,5-dihydrophenazine 
• 1353737-77-5 5-(4-chlorophenyl)-3-isopropylimino-2-(6-methyl-3-pyridyl)amino-3,5-dihydrophenazine 
• 1353737-99-1 5-(4-chlorophenyl)-3-(4-methoxycyclohexyl)imino-2-(2-methyl-3-pyridyl)amino-3,5-dihydrophenazine 
• 1353737-97-9 5-(4-chlorophenyl)-3-(4-tetrahydropyranyl)imino-2-(2-methyl-3-pyridyl)amino-3,5-dihydrophenazine 
• 1353737-90-2 5-(4-chlorophenyl)-3-isopropylimino-2-(2-methyl-3-pyridyl)amino-3,5-dihydrophenazine 
• 1353737-82-2 5-(4-chlorophenyl)-3-(4-methoxycyclohexyl)imino-2-(2-methoxy-3-pyridyl)amino-3,5-dihydrophenazine 

Relevant academic research and scientific papers

Optimization of the clofazimine structure leads to a highly water-soluble C3-aminopyridinyl riminophenazine endowed with improved anti-Wnt and anti-cancer activity in vitro and in vivo

Triple-negative breast cancer (TNBC) is a cancer subtype critically dependent upon excessive activation of Wnt pathway. The anti-mycobacterial drug clofazimine is an efficient inhibitor of canonical Wnt signaling in TNBC, reducing tumor cell proliferation

Clofazimine analogs with antileishmanial and antiplasmodial activity

A set of novel riminophenazine derivatives has been synthesized and evaluated for in vitro activity against chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains of Plasmodium falciparum and against different species of Leishmania promasti

Systematic evaluation of structure-activity relationships of the riminophenazine class and discovery of a C2 pyridylamino series for the treatment of multidrug-resistant tuberculosis

Clofazimine, a member of the riminophenazine class of drugs, is the cornerstone agent for the treatment of leprosy. This agent is currently being studied in clinical trials for the treatment of multidrug-resistant tuberculosis to address the urgent need for new drugs that can overcome existing and emerging drug resistance. However, the use of clofazimine in tuberculosis treatment is hampered by its high lipophilicity and skin pigmentation side effects. To identify a new generation of riminophenazines that is less lipophilic and skin staining, while maintaining efficacy, we have performed a systematic structure-activity relationship (SAR) investigation by synthesizing a variety of analogs of clofazimine and evaluating their anti-tuberculosis activity. The study reveals that the central tricyclic phenazine system and the pendant aromatic rings are important for anti-tuberculosis activity. However, the phenyl groups attached to the C2 and N5 position of clofazimine can be replaced by a pyridyl group to provide analogs with improved physicochemical properties and pharmacokinetic characteristics. Replacement of the phenyl group attached to the C2 position by a pyridyl group has led to a promising new series of compounds with improved physicochemical properties, improved anti-tuberculosis potency, and reduced pigmentation potential.

Identification of less lipophilic riminophenazine derivatives for the treatment of drug-resistant tuberculosis

Clofazimine (CFZ), a member of the riminophenazine class, has been studied in clinical trials for the treatment of multidrug-resistant tuberculosis (MDR-TB). CFZ has several side effects which can be attributed to its extremely high lipophilicity. A series of novel riminophenazine analogues bearing a C-2 pyridyl substituent was designed and synthesized with the goal of maintaining potent activity against Mycobacterium tuberculosis (M. tuberculosis) while improving upon its safety profile by lowering the lipophilicity. All compounds were evaluated for their in vitro activity and cytotoxicity. The results demonstrated that many new compounds had potent activity against M. tuberculosis with MICs of less than 0.03 μg/mL and low cytotoxicity with IC50 values greater than 64 μg/mL. Some compounds were tested for in vivo efficacy against MDR-TB in an experimental mouse infection model. Two compounds demonstrated equivalent or better efficacy than CFZ in this model with significantly reduced skin discoloration potential.

RIMINOPHENAZINES WITH 2-(HETEROARYL)AMINO SUBSTITUENTS AND THEIR ANTI-MICROBIAL ACTIVITY

The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

Synthesis of new riminophenazines with pyrimidine and pyrazine substitution at the 2-N position

New riminophenazines with pyrimidine and pyrazine substituents at the 2-position were successfully synthesized. The key step is the 2-N-arylation of riminophenazines with pyrimidine and pyrazine. The optimized reaction conditions involve the use of a Pds