117545-11-6

Basic information

• Product Name: Bimakalim
• Synonyms: Bimakalim;2,2-Dimethyl-4-(1,2-dihydro-2-oxopyridine-1-yl)-2H-1-benzopyran-6-carbonitrile;2,2-Dimethyl-6-cyano-4-[(1,2-dihydro-2-oxopyridin)-1-yl]-2H-1-benzopyran;6-Cyano-4-(2-oxo-1,2-dihydropyridine-1-yl)-2,2-dimethyl-2H-1-benzopyran;EMD-52692;SR-44866;2,2-dimethyl-4-(2-oxopyridin-1(2H)-yl)-2H-chromene-6-carbonitrile
• CAS NO: 117545-11-6
• Molecular Formula: C₁₇H₁₄N₂O₂
• Molecular Weight: 278.31
• Mol File: 117545-11-6.mol
• Article Data: 4

Chemical Properties

• Melting Point: 151 °C
• Boiling Point: 498.4°Cat760mmHg
• Flash Point: 255.2°C
• Appearance: /
• Density: 1.29g/cm³
• Vapor Pressure: 4.56E-10mmHg at 25°C
• Refractive Index: 1.651
• PKA: -0.32±0.23(Predicted)
• CAS DataBase Reference: Bimakalim(CAS DataBase Reference)
• NIST Chemistry Reference: Bimakalim(117545-11-6)
• EPA Substance Registry System: Bimakalim(117545-11-6)

Safety Data

• Hazardous Substances Data: 117545-11-6(Hazardous Substances Data)

Usage

Uses

Used in Cardiovascular Applications:
Bimakalim is used as a vasodilator for the treatment of cardiovascular diseases such as hypertension and angina. Its action on ATP-sensitive potassium channels in smooth muscle cells leads to vasodilation, which can help reduce blood pressure and alleviate chest pain associated with angina.
Used in Respiratory Applications:
Bimakalim is being studied for its potential use as a bronchodilator in the treatment of asthma and other respiratory conditions. Its ability to induce vasodilation may also contribute to improved lung function and reduced symptoms in these conditions.
Used in Smooth Muscle Dysfunction Applications:
Bimakalim is being investigated for its potential therapeutic effects in conditions related to smooth muscle dysfunction. Its action on potassium channels may help alleviate symptoms and improve the overall management of such conditions.
As research on Bimakalim progresses, its potential applications in various medical fields may continue to expand, offering new treatment options for a range of conditions.

InChI:InChI=1/C17H14N2O2/c1-17(2)10-14(19-8-4-3-5-16(19)20)13-9-12(11-18)6-7-15(13)21-17/h3-10H,1-2H3

Upstream product

• 142-08-5 2-Pyridone 
• 65018-90-8 3,4-epoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 
• 123596-63-4 trans-3,4-epoxy-3,4-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 
• 127806-78-4 6-Cyano-4-(1,2-dihydro-2-oxopyrid-1-yl)-2,2-dimethyl-3-oxochroman 
• 33143-29-2 6-cyano-2,2-dimethylchromene 
• 123595-75-5 3,4-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 

Downstream Products

• 123595-75-5 3,4-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 
• 123596-05-4 4-{(E)-2-[(3R,4S)-3-Hydroxy-2,2-dimethyl-4-(2-oxo-2H-pyridin-1-yl)-chroman-6-yl]-vinyl}-benzonitrile 
• 141602-60-0 3-<1-(1,2-dihydro-2-oxo-1-pyridyl)-3-methyl-1,2-butadienyl>-4-hydroxybenzonitrile 

Relevant articles and documents

2,2-dimethylchromene derivatives, process for their preparation and pharmaceutical compositions in which they are present

The present invention relates to 2,2-dimethylchromene derivatives of the formula: STR1 in which Z represents a halogen atom or a cyano, nitro, acetyl, phosphono or dialkoxyphosohoryl group, the alkoxy group containing 1 to 3 carbon atoms, and the pharmaceutically acceptable salts of the phosphono group. These compounds show an antihypertensive and antiarrythmic activity. The present invention also relates to a process for the preparation of said compounds and to the pharmaceutical compositions in which the are present.

Method of preparing chroman derivatives, and synthesis intermediates

The invention describes a method of synthesizing a compound of the formula STR1 in which X=O or NR, Z=an electron-attracting group, R=H, CN or NO2, R1 +R2 +N--C=X=a 5-membered or 6-membered heterocycle, and R3 =H, R4 =OH or R3 +R4 =a bond, said method involving intermediates of the formula STR2 in which R5 =H, Br or N(R1)CXR2. This method of synthesis does not involve the epoxide derivative of the chroman. The novel compounds of formula (IX) form a further subject of the invention.

Relaxant Activity of 4-Amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-Amido-2H-1-benzopyrans on Guinea Pig Isolated Trachealis

A series of 4-amido-3,4-dihydro-2H-benzopyran-3-ols and 4-amido-2H-1-benzopyrans related to the potassium channel activator cromakalim have been prepared and evaluated for their relaxant activity in guinea pig isolated tracheal spirals.Several analogues show enhanced relaxant activity relative to cromakalim in this preparation and the rank order of potency for those substituents investigated at C-6 was CF3>CN>C2H5>aza>=CH3.One compound, trans-3,4-dihydro-2,2-dimethyl-4-(2-oxopiperidin-1-yl)-7-(trifluoromethyl)-2H-1-benzopyran-3-ol (24), was resolved into its two enantiomers and the activity was shown to reside essentially in the (+)-isomer, adding further support to the suggestion that the smooth muscle receptor for these potassium channel activators is stereoselective.

Synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and related compounds, new potassium channel activators

The synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyran-3-ols are described. The unsubstituted pyridone adduct lead compound 7e is highly active, with substituents on the pyridone ring leading to a decrease in activity. Strongly electron-withdrawing substituents at the C-6 position are required for optimal activity. When the 2-pyridone ring is replaced by other heterocytes such as 4-pyridone, pyrimidone, pyridazinone, pyrazinone, and 1,4-butanesultam, the activity is maintained. The removal of the 3-hydroxy function (→17a) does not significantly reduce the activity. The elimination of water from the chromanols leads to the formation of the chromenes, which are among the most potent antihypertensives known. The influence of diverse substituents, in particular heterocyclic C-6 substituents, was investigated in the 4-(2-oxo-1-pyrrolidinyl)chroman-3-ol series. Chromanols esterified at the 3-hydroxy group with short-chain acids, maintain their activity. The epoxidation of the chromene double bond also produces active compounds. The rearrangement of the epoxides 22 produces the 3-keto compounds 23 and the enol derivatives 25. The reduction of the ketone 23a produces cis-chromanol 7ab along with its trans isomer 7e. All compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats with a dose of 1 mg/kg; for selected compounds ED30 values as well as the duration of the antihypertensive effect were determined. 4-(1,2-Dihydro-2-oxo-1-pyridyl) -2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (18a) is under development as a coronary vasodilator and a drug for treating angina pectoris.