6304-20-7

Usage

Uses

Used in Pharmaceutical Industry:
1-pyridin-4-ylbutan-2-one is used as a synthetic intermediate for the production of cardiotonic agents, specifically Milrinone (M344680) and Amrinone (A635000) analogues. These agents are designed to strengthen the contraction of the heart muscle, improving cardiac function in patients with heart failure or other related conditions. 1-pyridin-4-ylbutan-2-one's role in the synthesis process is crucial, as it contributes to the development of these life-saving medications.

InChI:InChI=1/C9H11NO/c1-2-9(11)7-8-3-5-10-6-4-8/h3-6H,2,7H2,1H3

Upstream product

• 108-89-4 picoline 
• 105-37-3 Ethyl propionate 
• 78-93-3 butanone 
• 79-03-8 propionyl chloride 

Relevant academic research and scientific papers

Discovery of potent and selective CDK8 inhibitors through FBDD approach

A fragment library screen was carried out to identify starting points for novel CDK8 inhibitors. Optimization of a fragment hit guided by co-crystal structures led to identification of a novel series of potent CDK8 inhibitors which are highly ligand efficient, kinase selective and cellular active. Compound 16 was progressed to a mouse pharmacokinetic study and showed good oral bioavailability.

NOVEL PYRROLE DERIVATIVES FOR THE TREATMENT OF CANCER

The invention provides a method for the treatment of cancer, which method comprises the general formula (I) wherein R1, R2, R3, R4 and W are as described herein.

Process for preparing certain 1-lower alkanoyl or benzoyl-4-(lower alkanoyl or benzoyl-methylidene)-1,4-dihydropyridines or acid addition salts thereof

There is described a novel process for preparing 4-pyridinylmethyl ketones of formula (I) STR1 wherein R is alkyl, aryl or aralkyl. The process involves hydrolysis of a compound STR2 generated by reaction of an acylating agent with 4-methylpyridine. The acylating agent may be selected from compounds of formula R-CO-X and R-CO-O-CO-R where R is as defined above and X represents halogen. Compounds of formula I have utility in the preparation of a variety of products, including pharmaceutically active 1,2-dihydro-6-R-2-oxo-5 pyridinyl compounds.

Bipyridine Cardiotonics: The Three-Dimensional Structures of Amrinone and Milrinone

The cardiotonic drug milrinone (1,6-dihydro-2-methyl-6-oxo--5-carbonitrile) is superior to its analogue amrinone (5-amino--6(1H)-one) by virtue of its greater potency and reduced side effect profile.We confirmed initial reports on the potencies of milrinone and amrinone and found that after intravenous administration to phenobarbital anesthetized dogs, the drug had cumulative inotropic ED50's of 37 and 1891 μg/kg, respectively; relative effects on heart rate and blood pressure were comparable.There are two structural differences between amrinone and milrinone: (1) milrinone has a pyridone 2-methyl substituent and (2) the pyridone 5-amino substituent of amrinone is replaced with a nitrile in milrinone.We confirmed structure-activity studies that indicated that the 2-methyl substituent appears to be primarily responsible for the dramatic difference in the potencies of amrinone and milrinone.A plausible explanation for the effect of the methyl substituent is an altered molecular topology resulting from its steric interaction with the 3',5'-hydrogen atoms.Consequently, we probed the three-dimensional structures of these two compounds by X-ray crystallography.The dihedral angle between the planes formed by the two aromatic rings of amrinone was 1.3 deg.In marked contrast, the corresponding angle for milrinone was 52.2 deg.Moreover, 1H NMR studies revealed conformational differences in solution.Whereas the 2-methyl substituent undoubtedly produces some electronic and hydrophobic perturbations in the bipyridine cardiotonic series, the most significant effect, from a global viewpoint, is the altered molecular topology.

5-(Pyridinyl)-1H-pyrazolo[3,4-b]pyridine-3-amines, their use as cardiotonics and their preparation

1-R-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridin-3-amines or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a 2-halo-5-PY-6-Q-nicotinonitrile with 1-R-hydrazine, where R is hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl or lower-alkoxyalkyl, Q is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Also shown are cardiotonic compositions and method for increasing cardiac contractility using said compounds or salts.

Synthetic Applications of N-N Linked Heterocycles. Part 8. Regiospecific Synthesis of 4-(α-Acylalkyl)pyridines by Attack of Lithium Enolates of Ketones γ to N-(2,6-Dimethyl-4-oxopyridin-1-yl)pyridinium Salts

The addition of N-(2,6-dimethyl-4-oxopyridin-1-yl)pyridinium salts (2) - (4) to lithium enolates (1) of ketones in tetrahydrofuran at low temperatures gives regiospecifically high yields of 1,4-dihydro-adducts (5) - (7).These are readily isolated and can be decomposed under free-radical conditions, also in high yield, to 4-(α-acylalkyl)pyridines (8) - (10).Unsymmetrical dialkyl ketones give a mixture of two isomeric products, the ratio depending upon reaction conditions and steric factors. αβ-Unsaturated ketones, however, give products resulting from reaction exclusively at the position α' to the carbonyl group.