16931-84-3

Usage

InChI:InChI=1/C12H15NO.ClH/c1-13(2)8-10-7-9-5-3-4-6-11(9)12(10)14;/h3-6,10H,7-8H2,1-2H3;1H

Upstream product

• 50-00-0 formaldehyd 
• 83-33-0 inden-1-one 
• 124-40-3 dimethyl amine 
• 30354-18-8 N,N-dimethyl(methylene)ammonium chloride 
• 506-59-2 N,N-dimethylammonium chloride 

Downstream Products

• 76283-82-4 2-[3-Oxo-3-phenyl-2-(toluene-4-sulfonyl)-propyl]-indan-1-one 
• 122431-67-8 trans-N,N-dimethyl-2,3-dihydro-1-phenoxyinden-2-methanamine 
• 122431-67-8 cis-N,N-dimethyl-2,3-dihydro-1-phenoxyinden-2-methanamine 
• 131704-00-2 trans-N,N-dimethyl-2,3-dihydro-1-(4-methoxyphenoxy)indene-2-methanamine oxalate 
• 131704-00-2 cis-N,N-dimethyl-2,3-dihydro-1-(4-methoxyphenoxy)indene-2-methanamine oxalate 
• 81471-49-0 2-Amino-5H-indeno<1,2-b>pyrid-3-yl-phenylketon 

Relevant academic research and scientific papers

Synthesis and anti-tubercular activity of conformationally-constrained and bisquinoline analogs of TMC207

One of the most significant breakthroughs in the battle against tuberculosis is the recent approval of the quinoline compound, TMC207, for the treatment of drug-resistant tuberculosis. To gain insight into the molecular determinants of the activity of TMC207 and to evaluate the scope of quinoline compounds as anti-tubercular agents, we synthesized a series of TMC207 derivatives and evaluated their anti-tubercular activity. Making the lateral chain of the drug rigid by linking it to an adjacent phenyl substituent resulted in a decrease in activity. In contrast, replacing a phenyl substituent of TMC207 with a quinoline moiety gave bisquinolines that demonstrated potent anti-tubercular activity in in vitro experiments, in ex vivo mouse bone marrow macrophage assays, and also in the in vivo mouse model of the disease. These results provide new guiding principles for modifying the TMC207 scaffold to develop efficacious anti-tubercular drugs and set the stage for the development of bisquinolines as a promising new class of anti-tubercular agents.

A New Method for the Synthesis of Ring-Fused Pyridines

An easy, one-step synthesis of pyridine derivatives 4 has been developed by condensation of enamines with iminium salts (Method A).This method could also be modified to yield unsymmetrically substituted derivatives (condensation of Mannich bases with ketones; Method B).

PROCESS FOR PREPARATION OF NORBORNENE DERIVATIVES

A method for producing a norbornene derivative, comprising: a first step of forming a Mannich base by reacting a carbonyl compound and an amine compound with each other in an acidic solvent, to thereby obtain a reaction liquid comprising the Mannich base in the acidic solvent, the acidic solvent comprising a formaldehyde derivative and 0.01 mol/L or more of an acid represented by the formula: HX (In the formula, X represents F or the like), the carbonyl compound being represented by any of the following general formulae (1) to (3): [in formulae (1) to (3), R1, R2, R3, R4, R5, and R6 each independently represent a hydrogen atom or the like, and n represents an integer of any of 0 to 4], the amine compound being represented by the following general formula (4): [in the formula (4), R7S each independently represent a linear chain saturated hydrocarbon group having 1 to 20 carbon atoms or the like, and X- represents F- or the like], the Mannich base being represented by any of the following general formulae (5) to (7): [R1, R2, R3, R4, R5, R6, and n in the formulae (5) to (7) have the same meanings as those of R1, R2, R3, R4, R5, R6, and n in the formulae (1) to (3), and R7 and X- in the formulae (5) to (7) have the same meanings as those of R7 and X- in the formula (4)] and a second step of reacting the Mannich base and a diene compound with each other by adding an organic solvent, a base in an amount of 1.0 to 20.0 equivalents to the acid, and the diene compound to the reaction liquid, and then heating the reaction liquid, to thereby form a norbornene derivative, the diene compound being represented by the following general formula (8): [in the formula (8), R8 represents a hydrogen atom or the like], the norbornene derivative being represented by any of the following general formulae (9) to (11): [R1, R2, R3, R4, R5, R6, and n in the formulae (9) to (11) have the same meanings as those of R1, R2, R3, R4, R5, R6, and n in the formulae (1) to (3), and R8 in the formulae (9) to (11) has the same meaning as that of R8 in the formula (8)].

Structure-activity relationships of dimethindene derivatives as new M2-selective muscarinic receptor antagonists

A series of 2,3-disubstituted indenes, which are analogues of the widely used histamine H1 receptor antagonist dimethindene, have been synthesized and studied as muscarinic and histamine receptor antagonists. The affinities of these compounds for the five human muscarinic receptor subtypes (M1-M5) and for human histamine H1 receptors were determined in radioligand binding studies using membranes from transfected Chinese hamster ovary (CHO) cells and [3H]N-methylscopolamine ([3H]NMS). The results demonstrate that the diisopropyl analogue 19 has a similar high affinity as (S)-dimethindene at M2 receptors ((S)-dimethindene: pKi = 7.52; (-)-19: pKi = 7.37) with an improved selectivity pattern ((S)-dimethindene: M2/M1 = 6-fold, M2/M3 = 5-fold, M2/M4 = 10-fold, M2/M5 = 25-fold; (-)-19: M2/M1 = 36-fold, M2/M3 = 96-fold, M2/M4 = 42-fold, M2/M5 = 275-fold). In addition, compound (-)-19 showed 35-fold lower affinity at histamine H1 receptors (pKi = 5.61) than (S)-dimethindene (pKi = 7.16). Another interesting compound is the fluoroethyl derivative 20 (pKi/M2 = 7.49), which also exhibits a higher M2 selectivity (M2/M1 = 19-fold; M2/M3 = 22-fold; M2/M4 13-fold; M2/M5 = 62-fold) than (S)-dimethindene. Unfortunately, compound 20 also shows a high affinity for histamine H1 receptors (pKi = 8.14). The compound with the highest affinity for M2 receptors (pKi = 7.91), the dimethylaminomethylene analogue 31, displayed only a small preference for M2 receptors. In conclusion, compound (-)-19 might be useful to test the hypothesis that blockade of muscarinic M2 receptors in the brain is a viable mechanism by which to produce improved cognition. This second-generation dimethindene analogue might also be the starting point for the development of M2-selective muscarinic antagonists useful for quantifying M2 receptors in the central nervous system with positron emission tomography imaging.

Facile synthesis of polycyclic pyridines, bipyridines, and oligopyridines

The preparation of polycyclic heterocycles with one or more nitrogen atoms and different binding angles by a domino reaction is described, These compounds (4-6, 8a-b) are formed by the reaction of β-amino ketone hydrochlorides 1 or 2 (Mannich bases) with ketones 3. Especially the synthesis of the terpyridines 8a and 8b in a double domino reaction is very useful (yield 70 and 59%) and opens a route to torands. VCH Verlagsgesellschaft mbH, 1996.

β-Amino Ketones as Key Intermediates in the Synthesis of Pyridines: A Novel and Efficient Route to Annelated Bi- and Terpyridines

The hydrochlorides of β-amino ketones 1a-e (Mannich bases) are easily obtained starting compounds for a novel synthesis of pyridines.Condensation with the heteroaromatic ketones 8, 9, and 10 yields 5,6-dihydro-1,10-phenanthrolines 3a-d, 13 and 4,5-diazafluorenes 4a-d, which have not yet been described in literature.Symmetrical terpyridines 3e, 4e are formed in a one-step reaction of 8, 9 with dimethylmethylenammonium chloride in the presence of an ammonia source.

Substituent Effect in Solvolysis of Spiro-1'-yl p-Nitrobenzoate

The preparation of a series of substituted spiro-1'-yl p-nitrobenzoates (4a-g) is described.The solvolysis rate constant is k = 8.53 * 10-5 s-1 at 25 deg C in 80percent aqueous acetone for the unsaturated derivative (4e) and is relatively high in comparison with the related secondary systems.The Hammett treatment (ρ?+) gives a straight line and the ρ value (-3.33) is more negative than that (-2.11) of 3,4-benzotricyclo1,6>-dec-3-en-2-anti-yl p-nitrobenzoate (1).On the basis of the results, it can be considered that the mesomeric transmission of substituent effect is very weak in 1 relative to 4.