168699-41-0

Upstream product

• 99-75-2 4-methyl-benzoic acid methyl ester 
• 874-60-2 4-methyl-benzoyl chloride 
• 1571-08-0 methyl 4-formylbenzoate 

Downstream Products

• 1129-35-7 4-cyanobenzoic acid methyl ester 
• 196301-94-7 methyl 4-(5-methyl-1,2,4-oxadiazol-3-yl)benzoate 
• 856251-61-1 4-[4-(4-tert-butylbenzoyl)-5-(4-cyclohexylphenyl)-4,5-dihydroisoxazol-3-yl]benzoic acid methyl ester 
• 856251-58-6 4-[5-(4-tert-butylbenzoyl)-4-(4-cyclohexylphenyl)-4,5-dihydroisoxazol-3-yl]benzoic acid methyl ester 
• 82544-82-9 methyl 4-(1H-tetrazole-5-yl)benzoate 
• 72331-27-2 4-oxycyano-benzoic acid methyl ester 
• 101023-70-5 4-methoxycarbonylbenzhydroxamic acid chloride 
• 1350759-88-4 tert-butyl 3-[4-(methoxycarbonyl)phenyl]-1-oxa-2,8-diazaspiro[4,5]dec-2-ene-8-carboxylate 

Relevant academic research and scientific papers

Visible-Light-Promoted Metal-Free Synthesis of (Hetero)Aromatic Nitriles from C(sp3)?H Bonds**

The metal-free activation of C(sp3)?H bonds to value-added products is of paramount importance in organic synthesis. We report the use of the commercially available organic dye 2,4,6-triphenylpyrylium tetrafluoroborate (TPP) for the conversion of methylarenes to the corresponding aryl nitriles via a photocatalytic process. Applying this methodology, a variety of cyanobenzenes have been synthesized in good to excellent yield under metal- and cyanide-free conditions. We demonstrate the scope of the method with over 50 examples including late-stage functionalization of drug molecules (celecoxib) and complex structures such as l-menthol, amino acids, and cholesterol derivatives. Furthermore, the presented synthetic protocol is applicable for gram-scale reactions. In addition to methylarenes, selected examples for the cyanation of aldehydes, alcohols and oximes are demonstrated as well. Detailed mechanistic investigations have been carried out using time-resolved luminescence quenching studies, control experiments, and NMR spectroscopy as well as kinetic studies, all supporting the proposed catalytic cycle.

Novel access to 2-substituted quinolin-4-ones by nickel boride-mediated reductive ring transformation of 5-(2-nitrophenyl)isoxazoles

Reductive ring transformation of 3-substituted 5-(2-nitrophenyl)isoxazoles, readily accessible via 1,3-dipolar cycloaddition of 2-ethinylnitrobenzene with nitrile oxides, opens a novel access to 2-substituted quinolin-4-ones. Nickel boride, generated in situ from nickel chloride and sodium borohydride, allows, via simultaneous reduction of the nitro group and reductive cleavage of the isoxazole ring, the one-step conversion into the target quinolin-4-ones. This protocol tolerates various functional groups, except olefins, and thus is complementary to the reductive ring transformation with iron/acetic acid, which predominantly tolerates olefins.

MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

Discovery of novel 5-oxa-2,6-diazaspiro[3.4]oct-6-ene derivatives as potent, selective, and orally available somatostatin receptor subtype 5 (SSTR5) antagonists for treatment of type 2 diabetes mellitus

Somatostatin receptor subtype 5 (SSTR5) has emerged as a novel attractive drug target for type 2 diabetes mellitus. Starting from N-benzyl azetidine derivatives 1 and 2 as in-house hit compounds, we explored the introduction of a carboxyl group into the t

An efficient catalytic method for the Beckmann rearrangement of ketoximes to amides and aldoximes to nitriles mediated by propylphosphonic anhydride (T3P)

An efficient method for the Beckmann rearrangement of ketoximes to amides mediated by a catalytic amount (15 mol %) of propylphosphonic anhydride (T3P) is described. Aldoximes underwent second order Beckmann rearrangement to provide the corresponding nitriles in excellent yields on reacting with T3P (15 mol %) at room temperature. The main advantages of this environmentally friendly protocol include procedural simplicity, and particularly ease of isolation of the products.

SPIRO ISOXAZOLINE COMPOUNDS AS SSTR5 ANTAGONISTS

Substituted spirocyclic amines of structural formula (I) are selective antagonists of the somatostatin subtype receptor 5 (SSTR5) and are useful for the treatment, control or prevention of disorders responsive to antagonism of SSTR5, such as Type 2 diabetes, insulin resistance, lipid disorders, obesity, atherosclerosis, Metabolic Syndrome, depression, and anxiety.

Novel echinocandin antifungals. Part 2: Optimization of the side chain of the natural product FR901379. Discovery of micafungin

Further optimization of the potent antifungal activity of side chain analogs of the natural product FR901379 led to the discovery of compound 8 with an excellent, well-balanced profile. Potent compounds with reduced hemolytic potential were designed based upon a disruption of the linearity of the terphenyl lipophilic side chain. The optimized compound (8, FK463, micafungin) displayed the best balance and was selected as the clinical candidate.

NOVEL GLUCAGON ANTAGONISTS/INVERSE AGONISTS

Novel compounds that act to antagonize the action of the glucagon peptide hormone on the glucagon receptor. More particularly, it relates to glucagon antagonists or inverse agonists.

Reactivity of p-substituted benzaldoximes in the cleavage of p-nitrophenyl acetate: Kinetics and mechanism

Eleven p-substituted benzaldoximes (p-XC6H4CH=NOH, where X = H, CH3, CF3, F, Cl, Br, OCH3, N(CH3)2, COOCH3, CN, NO2) have been synthesized and their dissociation constants determined in 10% (v/v) aqueous dioxane at 35°C. Under the same conditions, the pseudofirst order rate constants kobs of their reactions with p-nitrophenyl acetate (PNPA) were measured at pH values from 7.8 to 10.8 and at concentrations c oxime ranging from 0 to 4:00 x 10-3 mol l-1. The kinetic model and mechanism of the said reaction was proposed by means of mathematical statistical modelling of the dependences of kobs on pH and coxime. The mechanism involves a pre-equilibrium (k -1/k1) in which PNPA forms a tetrahedral intermediate (THI) with the deprotonated form of oxime. In the given medium, THI is in equilibrium with the non-reactive conjugated acid THIH (dissociation constant Ka,THIH) which is stabilized by intramolecular hydrogen bond. Depending on pH, the rate-limiting step consists either in formation of THI from educts (pH a,oxime) or in its spontaneous (k 2) and oxime-catalyzed (k3, general acid catalysis) decomposition to products (pH > pKa/oxime). Evaluation of substituent effects on dissociation constants (Ka,oxime) of the oximes showed that there is no direct conjugation between the substituent and the reaction centre (the found reaction constant ρ(Ka,oxime) = 0.91). The transmission coefficient of the transfer of these effects through C=N-O grouping corresponds approximately to one bond. The reaction constants in the Hammett equation obtained from the regression model are: ρ(k -1Ka,THIH/k1) = 1.29, ρ(k2K a,THIH) = 0.20 and ρ(k3Ka,THIH) = 0.67. These reaction constants have been discussed with the regard to the reaction mechanism suggested.

SUBSTITUTED (AMINOIMINOMETHYL OR AMINOMETHYL) BENZOHETEROARYL COMPOUNDS

This invention is directed to an (aminoiminomethyl or aminomethyl) benzoheteroaryl compound of formula I which is useful for inhibiting the activity of Factor Xa by combining said compound with a composition containing Factor Xa. The present invention is also directed to compositions containing compounds of the formula I, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.