26163-03-1

Usage

Chemical Properties

Cream powder

Synthesis Reference(s)

Tetrahedron, 51, p. 8649, 1995 DOI: 10.1016/0040-4020(95)00478-Q

InChI:InChI=1/C5H4BrFN2/c6-4-1-3(7)2-9-5(4)8/h1-2H,(H2,8,9)

Upstream product

• 1072-98-6 5-chloro-2-pyridylamine 
• 504-29-0 2-aminopyridine 
• 171774-38-2 N-(3-bromo-5-chloropyridin-2-yl)pyridin-1-ium-1-aminide 

Downstream Products

• 217090-19-2 5-chloro-3-(4-methylthiophenyl)-2-pyridinamine 
• 301542-52-9 5-Chloro-3-[(E)-2-(2-pyridinyl)ethenyl]-2-pyridinamine 
• 301542-50-7 5-chloro-3-[(E)-2-phenylethenyl]-2-pyridinamine 
• 301542-51-8 5-Chloro-3-[(E)-2-(4-methoxyphenyl)ethenyl]-2-pyridinamine 
• 301542-53-0 5-Chloro-3-[(E)-2-cyclohexylethenyl]-2-pyridinamine 
• 64945-22-8 5-chloro-3-(2-methoxy-ethoxy)-pyridin-2-ylamine 
• 301542-40-5 t-butyl (E)-3-(2-amino-5-chloro-3-pyridinyl)-2-propenoate 
• 301542-54-1 3-[(E)-2-(2-Amino-5-chloro-3-pyridinyl)ethenyl]benzonitrile 
• 301542-56-3 5-Chloro-3-(2-phenylethynyl)-2-pyridinamine 
• 301542-55-2 3-[(E)-2-(1,3-Benzodioxol-5-yl)ethenyl]-5-chloro-2-pyridinamine 
• 301542-57-4 5-Chloro-3-phenoxy-2-pyridinamine 
• 130532-92-2 5-chloro-3-phenyl-pyridin-2-ylamine 
• 137628-17-2 2,3-dibromo-5-chloro-pyridine 
• 1005499-39-7 3-[(3-bromo-5-chloropyridin-2-yl)amino]cyclohex-2-en-1-one 

Relevant academic research and scientific papers

8-Alkynyl-3-nitroimidazopyridines display potent antitrypanosomal activity against both T. b. brucei and cruzi

An antikinetoplastid pharmacomodulation study was done at position 8 of a previously identified pharmacophore in 3-nitroimidazo[1,2-a]pyridine series. Twenty original derivatives bearing an alkynyl moiety were synthesized via a Sonogashira cross-coupling reaction and tested in vitro, highlighting 3 potent (40 nM ≤ EC50 blood stream form≤ 70 nM) and selective (500 ≤ SI ≤ 1800) anti-T. brucei brucei molecules (19, 21 and 22), in comparison with four reference drugs. Among these hit molecules, compound 19 also showed the same level of activity against T. cruzi (EC50 amastigotes = 1.2 μM) as benznidazole and fexinidazole. An in vitro comet assay showed that nitroaromatic derivative 19 was not genotoxic. It displayed a low redox potential value (?0.68 V/NHE) and was shown to be bioactivated by type 1 nitroreductases both in Leishmania and Trypanosoma. The SAR study indicated that an alcohol function improved aqueous solubility while maintaining good activity and low cytotoxicity when the hydroxyl group was at position beta of the alkyne triple bond. Hit-compound 19 was also evaluated regarding in vitro pharmacokinetic data: 19 is BBB permeable (PAMPA assay), has a 16 min microsomal half-life and a high albumin binding (98.5percent). Moreover, compound 19 was orally absorbed and was well tolerated in mouse after both single and repeated administrations at 100 mg/kg. Its mouse plasma half-life (10 h) is also quite encouraging, paving the way toward further efficacy evaluations in parasitized mouse models, looking for a novel antitrypanosomal lead compound.

8-Aryl-6-chloro-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridines as potent antitrypanosomatid molecules bioactivated by type 1 nitroreductases

Based on a previously identified antileishmanial 6,8-dibromo-3-nitroimidazo[1,2-a]pyridine derivative, a Suzuki-Miyaura coupling reaction at position 8 of the scaffold was studied and optimized from a 8-bromo-6-chloro-3-nitroimidazo[1,2-a]pyridine substrate. Twenty-one original derivatives were prepared, screened in vitro for activity against L. infantum axenic amastigotes and T. brucei brucei trypomastigotes and evaluated for their cytotoxicity on the HepG2 human cell line. Thus, 7 antileishmanial hit compounds were identified, displaying IC50 values in the 1.1–3 μM range. Compounds 13 and 23, the 2 most selective molecules (SI = >18 or >17) were additionally tested on both the promastigote and intramacrophage amastigote stages of L. donovani. The two molecules presented a good activity (IC50 = 1.2–1.3 μM) on the promastigote stage but only molecule 23, bearing a 4-pyridinyl substituent at position 8, was active on the intracellular amastigote stage, with a good IC50 value (2.3 μM), slightly lower than the one of miltefosine (IC50 = 4.3 μM). The antiparasitic screening also revealed 8 antitrypanosomal hit compounds, including 14 and 20, 2 very active (IC50 = 0.04–0.16 μM) and selective (SI = >313 to 550) molecules toward T. brucei brucei, in comparison with drug-candidate fexinidazole (IC50 = 0.6 & SI > 333) or reference drugs suramin and eflornithine (respective IC50 = 0.03 and 13.3 μM). Introducing an aryl moiety at position 8 of the scaffold quite significantly increased the antitrypanosomal activity of the pharmacophore. Antikinetoplastid molecules 13, 14, 20 and 23 were assessed for bioactivation by parasitic nitroreductases (either in L. donovani or in T. brucei brucei), using genetically modified parasite strains that over-express NTRs: all these molecules are substrates of type 1 nitroreductases (NTR1), such as those that are responsible for the bioactivation of fexinidazole. Reduction potentials measured for these 4 hit compounds were higher than that of fexinidazole (?0.83 V), ranging from ?0.70 to ?0.64 V.

Flexible on-site halogenation paired with hydrogenation using halide electrolysis

Direct electrochemical halogenation has appeared as an appealing approach in synthesizing organic halides in which inexpensive inorganic halide sources are employed and electrical power is the sole driving force. However, the intrinsic characteristics of direct electrochemical halogenation limit its reaction scope. Herein, we report an on-site halogenation strategy utilizing halogen gas produced from halide electrolysis while the halogenation reaction takes place in a reactor spatially isolated from the electrochemical cell. Such a flexible approach is able to successfully halogenate substrates bearing oxidatively labile functionalities, which are challenging for direct electrochemical halogenation. In addition, low-polar organic solvents, redox-active metal catalysts, and variable temperature conditions, inconvenient for direct electrochemical reactions, could be readily employed for our on-site halogenation. Hence, a wide range of substrates including arenes, heteroarenes, alkenes, alkynes, and ketones all exhibit excellent halogenation yields. Moreover, the simultaneously generated H2at the cathode during halide electrolysis can also be utilized for on-site hydrogenation. Such a strategy of paired halogenation/hydrogenation maximizes the atom economy and energy efficiency of halide electrolysis. Taking advantage of the on-site production of halogen and H2gases using portable halide electrolysis but not being suffered from electrolyte separation and restricted reaction conditions, our approach of flexible halogenation coupled with hydrogenation enables green and scalable synthesis of organic halides and value-added products.

Directing Group Enables Electrochemical Selectively Meta-Bromination of Pyridines under Mild Conditions

Without the use of catalysts and oxidants, a facile and sustainable electrochemical bromination protocol was developed. By introducing the directing groups, the regioselectivity of pyridine derivatives could be controlled at themeta-position utilizing the inexpensive and safe bromine salts at room temperature. A variety of brominated pyridine derivatives were obtained in 28-95% yields, and the reaction could be readily performed at a gram scale. By combining the installation and removing the directing group, the concept ofmeta-bromination of pyridines could be verified.

Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis

The histamine H4 receptor (H4R), a member of the G-protein coupled receptor family, has been considered as a potential therapeutic target for treating atopic dermatitis (AD). A large number of H4R antagonists have been disclosed, but no efficient agents controlling both pruritus and inflammation in AD have been developed yet. Here, we have discovered a novel class of orally available H4R antagonists showing strong anti-itching and anti-inflammation activity as well as excellent selectivity against off-targets. A pharmacophore-based virtual screening system constructed in-house successfully identified initial hit compound 9, and the subsequent homology model-guided optimization efficiently led us to discover pyrido[2,3-e]tetrazolo[1,5-a]pyrazine analogue 48 as a novel chemotype of a potent and highly selective H4R antagonist. Importantly, orally administered compound 48 exhibits remarkable efficacy on antipruritus and anti-inflammation with a favorable pharmacokinetic (PK) profile in several mouse models of AD. Thus, these data strongly suggest that our compound 48 is a promising clinical candidate for treatment of AD.

A 2-amino-3-bromo-5-chloro-pyridine synthesis method

The invention belongs to the field of organic synthesis and in particular relates to a synthetic method of 2-amino-3-bromo-5-chloropyridine. The synthetic method comprises the following steps: reacting raw materials 2-amino-5-chloropyridine and N-bromosuccinimide with a molar weight of 1: (0.4-4) in a proper solvent for 0.5-24 hours at 1-100 DEG C to generate a 2-amino-3-bromo-5-chloropyridine crude product, and purifying to obtain the pure product 2-amino-3-bromo-5-chloropyridine. The synthetic method has the beneficial effects that the reaction raw materials are available and are reasonable in prices; meanwhile, heavy metals and corrosive gases are not used in the preparation reaction; the reaction is mild; the synthetic method does not have special requirements for reaction equipment and common corrosion resistant equipment can be used for production; besides, with the advantageous conditions such as moderate reaction conditions, easily controlled reaction and high product purity, the process is easy to popularize.

HETEROCYCLIC COMPOUND

The present invention provides a compound or a salt thereof useful for an agent for the prophylaxis or treatment of neurodegenerative disease and the like. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.

NOVEL HETEROCYCLIC DERIVATIVES AND THEIR USES

The present invention relates to novel heterocyclic compounds useful in preparing drugs for treatment of diseases associated with various functions of the histamine 4 receptor. Especially, the said drugs are useful for treatment of inflammatory diseases, allergy, pain, nasal polyps, rhinitis, chronic sinusitis, nasal congestion, nasal itch, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis, eczema, pruritus, itchy skin, urticaria, idiopathic chronic urticaria, scleroderma, conjunctivitis, keratoconjunctivitis, ocular inflammation, dry eye, cardiac dysfunction, arrhythmia, atherosclerosis, multiple sclerosis, inflammatory bowel disease (including colitis, Crohn's disease, ulcerative colitis), inflammatory pain, neuropathic pain, osteoarthritic pain, autoimmune thyroid disease, immune-mediated (also known as type I) diabetes, lupus, post-operative adhesions, vestibular disorders and cancer.

2-AMINOPYRIDINE ANALOGS AS GLUCOKINASE ACTIVATORS

Provided are compounds of formula I that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes meilitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.

2-AMINOPYRIDINES AS INHIBITORS OF CYCLOOXYGENASE-2

The invention encompasses the novel compound of Formula (I) as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula (I). The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula (I).