76568-02-0 Usage
Uses
Used in Pharmaceutical Industry:
Flosequinan is used as a vasodilator for the treatment of congestive heart failure in patients who are intolerant to ACE inhibitors or for those who are also taking ACE inhibitors. Its unique mechanism of action, without causing reflex stimulation of the renin-angiotensin or sympathetic nervous system, makes it a valuable addition to the treatment options for heart failure.
Used in Cardiology:
Flosequinan is used as a therapeutic agent for managing congestive heart failure, helping to improve blood flow and reduce the workload on the heart. Its once-daily administration due to its long half-life makes it a convenient and effective option for patients with this condition.
Manufacturing Process
7-Fluoro-3-methylsulphinyl-4-quinolone (5.0 g) was dissolved in hot butanone
(250 ml) containing anhydrous potassium carbonate (3.06 g). The resulting
suspension was stirred and treated dropwise with dimethyl sulphate (2.09 ml).
The mixture was stirred and boiled under reflux for 1 hour and filtered while
hot. The filtrate was allowed to cool, giving a crystalline product. The product
was collected and dried to give 7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone, melting point 226-228°C.The intermediate 7-fluoro-3-methylsulphinyl-4-quinolone, was prepared in the
following way:A solution of 2-amino-4-fluorobenzoic acid (62 g) in aqueous sodium
carbonate (44 g sodium carbonate in 1.6 liters water) was stirred and treated
dropwise with a solution of phosgene (120 g) in toluene (500 ml) during 1.5
hours. The resulting suspension was stirred at room temperature for 24 hours.
The solid product was collected by filtration, washed with water and dried to
give 7-fluoro-1,2-dihydro-3,1(4H)-benzoxazine-2,4-dione; melting point 217-
219°C.A mixture of dimethyl sulphoxide (230 ml), toluene (300 ml) and 50% w/w
dispersion of sodium hydride in mineral oil (20.7 g) was heated under
nitrogen at 65-70°C for 1 hour, then cooled to room temperature to form
dimethylsulphoxide anion, sodium salt. The resulting suspension was stirred
under nitrogen and the above benzoxazine-2,4-dione (27.5 g) was added
portionwise. The resulting solution was stirred at room temperature for 15
minutes and then poured into ether (3 liters). The resulting solid was collected
by filtration and dissolved in water (300 ml) and the solution acidified with
glacial acetic acid to a final pH of 6.0. The solution was saturated with solid
potassium carbonate. The resulting precipitate was collected, dried and
recrystallised from ethanol/diethyl ether to give the novel compound 2'-
amino-4'-fluoro-(2-methylsulphinyl)acetophenone, melting point 115-117°C.This compound (14 g) was dissolved in triethyl orthoformate (160 ml) at
100°C under nitrogen. The resulting solution was treated dripwise with
piperidine (7 ml). The mixture was heated with stirring at 120°C under
nitrogen for 30 min allowing ethanol produced to distil off, then cooled to
room temperature. The solid product was collected, dried and crystalized from
ethanol using charcoal to give the 7-fluoro-3-methylsulphinyl-4-quinolone;
melting point 265°C.
Therapeutic Function
Antihypertensive, Vasodilator
Check Digit Verification of cas no
The CAS Registry Mumber 76568-02-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,6,5,6 and 8 respectively; the second part has 2 digits, 0 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 76568-02:
(7*7)+(6*6)+(5*5)+(4*6)+(3*8)+(2*0)+(1*2)=160
160 % 10 = 0
So 76568-02-0 is a valid CAS Registry Number.
InChI:InChI=1/C11H10FNO2S/c1-13-6-10(16(2)15)11(14)8-4-3-7(12)5-9(8)13/h3-6H,1-2H3
76568-02-0Relevant articles and documents
Syntheses of Flosequinan: A Novel 4-Quinolone shown to be useful in Congestive Heart Failure
Birch, Alan M.,Davies, Roy V.,Maclean, Lachlan,Robinson, Keith
, p. 387 - 392 (2007/10/02)
Two synthetic routes to flosequinan 1 and flosequinoxan 2 are described in which either ring closure of the β-keto sulfoxides 12 or 13 with ortho esters or cyclisation of the anilinoacrylates 23, 28 or 29 are the key steps.
Process for the preparation of 1-methyl-3-methylthio-4-quinolone and the sulfinyl, and sulfonyl analogs thereof
-
, (2008/06/13)
A process to prepare compounds of formula I STR1 in which n=0, 1 or 2 comprising the cyclisation of compounds of formula II STR2 in which n=0, 1 or 2. The cyclisation may be effected in the presence of an organic or inorganic base or thermally at a temper
Method of treating heart disease
-
, (2008/06/13)
A method for the treatment of heart failure in a mammal comprises the administration to the mammal of a quinolone of the general formula I, STR1 wherein m is 0 or 1; n is 0, 1 or 2; and R is hydrogen, halo, methyl or trifluoromethyl. A preferred method of the invention comprises the treatment of chronic heart failure in a mammal by the oral administration of a quinolone of formula I. Preferred compounds of formula I are 7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone and 1-methyl-3-methylsulphonylmethyl-4-quinolone.
4-Quinolinones having antihypertensive activity
-
, (2008/06/13)
Compositions which contain a quinolone compound of the general formula STR1 wherein n is 0, 1 or 2; R1 is lower alkyl optionally substituted by hydroxy or C1-4 alkoxycarbonyl; allyl; propynyl or phenyl- lower alkyl in which the phenyl ring is optionally substituted by 1 or 2 C1-4 alkoxy groups; R2 is C1-4 alkyl with the proviso that when n is 0, R2 is methyl; and R3, R4 and R5, which may be the same or different, are hydrogen, lower alkyl, lower alkoxy, lower alkanoyl, halo, trifluoromethyl or lower alkylthio show antihypertensive activity. Compounds of general formula STR2 in which n, R1 R2, R3, R4 and R5 are as described above are novel subject to the following provisos (a) when R3, R4 and R4 and R5 are hydrogen R2 is methyl and R1 is lower alkyl, R1 contains more than one carbon atom, and (b) when R3 and R4 are hydrogen, R5 is hydrogen or 7-methyl, and R1 is ethyl, R2 contains more than one carbon atom. The specification describes and claims methods of making the compounds and novel intermediates used in such methods.
