Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1990-04-20
1991-07-02
Springer, David B.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514311, 576153, 576155, 576156, 576172, 576175, 576171, 576178, 576179, 576180, C07D21512, C07D21514, C07D40307, A61K 3147
Patent
active
050286153
DESCRIPTION:
DESCRIPTION
EXAMPLE 1
4-(2-QUINOLINYLMETHLOXY)BENZALDEHYDE
A solution of 0.65 g (5.4 mmol) 4-hydroxybenzaldehyde, 0.94 g (5.3 mmol) of 2-quinolinylmethylchloride, and 0.75 g (5.4 mmol) of potassium carbonate in 15 ml of DMF is heated at 60.degree. C. overnight. The reaction mixture is poured into water. The precipitate is collected on a filter and purified by dry column chromatography to give 4-(2-quinolinylmethyloxy)benzaldehyde.
EXAMPLE 2
When 3-hydroxybenzaldehyde of Example I is replaced by the compounds of Table I below, then the corresponding product is obtained.
TABLE I
EXAMPLE 3
When 2-quinolinylmethyl chloride of Example 1 above is replaced by the quinoline compounds of Table II below then the corresponding product is obtained.
TABLE II
EXAMPLE 4
When 2-quinolinylmethylchloride of Example 1 is replaced by the compounds of Table II, Example 3 and 4-hydroxybenzaldehyde of Example 1 is replaced by the compounds of Table I, Example 2 then the corresponding product is obtained.
EXAMPLE 5
4-(4-(2-QUINQLINYLMETHYLOXY)STYRYL)BENZONITRILE
A suspension of 5.51 g (13.29 mmol) of (4-cyanobenzyl)-triphenylphosphonium chloride in 100 ml of dry DMF under positive nitrogen atmosphere is cooled to 0.degree. C. and 0.50 g (20.77 mmol) of an 80% NaH in oil dispersion is added in o small portions. The suspension is aged for 15 minutes at 0.degree. C. followed by 45 minutes at room temperature to assure complete anion formation. The flask is cooled back to 0.degree. C. and 3.5 g (13.29 mmol) of 4-(2-quinolinylmethyloxy)benzaldehyde in 20 ml of DMF is dropped in over a period of 15 minutes. The reaction is allowed to equilibrate to room temperature and stirred for 2 hours. The resultant mixture is poured into ice water and filtered. The precipitate is dissolved in CH.sub.2 Cl.sub.2, dried, and concentrated in vacuo. The crude product is recrystallized from ether to give 4-(4-(2- quinolinylmethyloxy)styryl)benzonitrile. (M.P. 116.degree. C.-112 .degree. C.)
EXAMPLE 6
When (4-cyanobenzyl)triphenylphosphonium chloride is replaced by the compounds of Table III below then the corresponding products are prepared.
TABLE VI
EXAMPLE 7
When the Wittig reagents of Table III, Example 6 are reacted with the compounds prepared by Examples 3 and 4 following the procedure of Example 5 then the corresponding products are obtained.
EXAMPLE 8
5-(4-(4-(2-QUINOLINYLMETHYLOXY)STYRYL)PHENYL)TETRAZOLE
A mixture of 1.15 g (3.17 mmol) of 4-(4-(2-quinolinylmethyloxy)styryl)benzonitrile 1.03 q (15.86 mmol) of sodium azide, and 1.83 (15.86 mml) of pyridine hydrochloride in 15 ml of DMF is heated at 100.degree. C. for 48 hours and then poured into ice water. The precipitate that forms is filtered off and suspended in hot methanol and filtered to give 5-(4-(4- (2-quinolinylmethyloxy)styryl)phenyl)tetrazole. (M.P. 241.degree. C.-243.degree. C.)
EXAMPLE 9
When 4-(4-(2-quinolinylmethyloxy)styryl)benzonitrile of Example 8 is replaced by the nitriles of Examples 6 and 7, then the corresponding product is obtained. A representative list of compounds so prepared is shown in Table IV, below.
TABLE IV
EXAMPLE 10
When (4-cyanobenzyl)triphenylphosphonium chloride of Example 5 is replaced by (4-carboxybenzyl)triphenylphosphonium chloride then the product prepared is 4-(4-(2-quinolinylmethyloxy)styryl)benzoic acid.
In a similar manner, the various carboxylic acids of this invention may be prepared.
EXAMPLE 11
When the esters of Example 10 are used in place of the carboxylic acids then the corresponding product is obtained.
EXAMPLE 12
4-(4-(2-QUINOLINYLMETHYLOXY)STYRYL)BENZOYL CHLORIDE
To 0.05 mol of 4-(4-(2-quinolinylmethyloxy)styryl) benzoic acid in dichloromethane solution (500 ml), chilled in an ice bath, is added thionyl chloride (0.06 mol) and a few drops of dimethylformamide. Upon completion of the reaction, the clear solution is evaporated to give 4-(4-(2-quinolinylmethyloxy)styryl)benzoyl choride.
In a similar manner, the various acid halides of this invention may be prepared.
EXAMPLE 13
4-(4-(2-QUINOLINY
REFERENCES:
patent: 4918081 (1990-04-01), Huang et al.
patent: 4920130 (1990-04-01), Huang et al.
patent: 4920131 (1990-04-01), Huang et al.
patent: 4920132 (1990-04-01), Huang et al.
patent: 4920133 (1990-04-01), Huang et al.
patent: 4977162 (1990-12-01), Huang et al.
Campbell Henry F.
Galemmo, Jr. Robert A.
Huang Fu-chi
Barron Alexis
Nicholson James A.
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Savitzky Martin F.
Springer David B.
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