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Afloqualone, アフロクアロン

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Afloqualone.pngChemSpider 2D Image | Afloqualone | C16H14FN3OAfloqualone.svg

Afloqualone

Molecular Formula: C16H14FN3O
Molecular Weight: 283.306 g/mol

6-amino-2-(fluoromethyl)-3-(2-methylphenyl)quinazolin-4-one

HQ 495C033541, QA-3735, UNII:CO4U2C8ORZ

4(3H)-Quinazolinone, 6-amino-2-(fluoromethyl)-3-(2-methylphenyl)- [ACD/Index Name]
4831
56287-74-2 [RN], アフロクアロン

Afloqualone; 56287-74-2; Arofuto; Aroft; Afloqualon; Afloqualone [INN:JAN]

Afloqualone (Arofuto) is a quinazolinone family GABAergic drug and is an analogue of methaqualone developed in the 1970s by a team at Tanabe Seiyaku.[1] It has sedative and muscle-relaxant effects resulting from its agonist activity at the β subtype of the GABAareceptor ,[2] and has had some clinical use, although it causes photosensitization as a side-effect that can cause skin problems such as dermatitis.[3]

PATENT

CN 106496145

PATENT

CN 106496144

https://patents.google.com/patent/CN106496144A/en

Example 1:

[0027] A-fluoro-quinolin-one process, comprising the steps of:

[0028] A. To the hydrogenation apparatus 10g 6- nitro-2- (fluoromethyl) -3- (2-methylphenyl) -4- (3H) -1,3- phthalazinone , 150ml acid content of 0.1 ~ 0.4N n-butanol solution of acetic acid, lg palladium ruthenium bimetallic catalyst, hydrogen pressure 0.02 ~ 0.4MPa, reaction temperature of 25-50 ° C, after 1 hour, filtered to give the filtrate ;

[0029] B. washed catalyst with ethanol, at normal temperature, under reduced pressure to obtain a solution ⑴;

[0030] C. was added to the filtrate and the solution ⑴ water, 0.1N sodium hydroxide solution was added, the pH adjusted to 10.2 to 11.0, and stirred at 50-60 ° C 0.5 h, cooled to room temperature and filtered to give the crude fluoro-quinolin-one;

[0031] D.-fluoro-quinolin per gram of the recrystallization solvent was added 5 ~ 15ml crude ketone, wherein the recrystallization solvent is a volume ratio of 1: 1: 0.2 in a solution of isopropanol (m), a solution of acid butyl ester (II ) and water mixture; crystallized at room temperature, filtered to give a fluorine methaqualone.

[0032] Example 2:

[0033] A-fluoro-quinolin-one process, comprising the steps of:

[0034] A. hydrogenation apparatus added to 20g 6- nitro _2_ (fluoromethyl) -3- (2_-methylphenyl) -4- (3-1,3-phthalazinone buckle, acid content of the acid-containing 240ml 0.1 ~ 0.4N ethanol solution of hydrochloric acid, lg palladium ruthenium bimetallic catalyst, hydrogen pressure 0.02 ~ 0.4MPa, reaction temperature of 25-50 ° C. after 0.5 hours the reaction was filtered to obtain filtrate;

[0035] B. washed catalyst with ethanol, at normal temperature, under reduced pressure to obtain a solution ⑴;

[0036] C. was added to the filtrate and the solution ⑴ water, 0.1N sodium hydroxide solution was added, the pH adjusted to 10.2 to 11.0, and stirred at 50-60 ° C 1 hour, cooled to room temperature and filtered to give the crude fluoro-quinolin-one;

[0037] D.-fluoro-quinolin added per gram of crude ketone was recrystallized from 5 ~ 15ml of the solvent, wherein the recrystallization solvent is a volume ratio of 1: o.2: methanol solution of i (m), an ethyl acetate solution (II ) and water mixture; crystallized at room temperature, filtered to give a fluorine methaqualone.

[0038] Example 3:

[0039] – quinolin-fluoro-one kind of process, comprising the steps of:

[0040] A. Add 5g 6- nitro apparatus _2_ hydride (fluoromethyl) -3- (2-methylphenyl) -4- (3-1,3-Perot phthalazinone, 80ml methanol containing an acid in an amount of 0.1 ~ 0.4N solution of sulfuric acid, lg palladium ruthenium bimetallic catalyst, hydrogen pressure 0.02 ~ 0.4MPa, reaction temperature of 25-50 ° C. after 1.5 hours the reaction was filtered to obtain filtrate;

[0041] B. the catalyst was washed with ethanol, normal temperature under reduced pressure to obtain a solution (the I);

[0042] C. was added to the filtrate and the solution (I) water, 0.1N sodium hydroxide solution was added, the pH adjusted to 10.2 to 11.0, and stirred at 50-60 ° C 1 hour, cooled to room temperature and filtered to give fluoro-quinolin-one Crude;

[0043] D. methaqualone fluorine per gram of crude product were added 5 ~ 15ml recrystallization solvent, wherein the recrystallization solvent is a volume ratio of 1: 0.2: 0.2 ethanol solution (m), carboxylic acid butyl ester (II) and water mixture; crystallization at room temperature, and filtered to give fluoro-quinolin-one.

PAPER

6-Amino-2-(fluoromethyl)-3-(2-methylphenyl)quinazolin-4(3H)-one
Acta Crystallographica, Section E: Structure Reports Online (2007), 63, (7), o3109

http://scripts.iucr.org/cgi-bin/paper?S1600536807026670

PAPER

Synthesis of the metabolites of afloqualone and related compounds
Chemical & pharmaceutical bulletin (1983), 31, (4), 1158-65.

Seven main metabolites (3-9) of afloqualone (1, 6-amino-2-fluoromethyl-3-(o-tolyl)-4 (3H)-quinazolinone and related 4 (3H)-quinazolinone derivatives were synthesized. The metabolites 4 and 5 containing a sulfur atom were prepared by the reaction of 6-acetamido-2-chloromethyl-3-(o-tolyl)-4 (3H)-quinazolinone (11) with NaSCH3 followed by oxidation with H2O2. Reaction of 11 and N-acetyl-L-cysteine gave the mercapturic acid-conjugated metabolite 6. Condensation of 2-fluoroacetamido-5-nitrobenzoic acid (19) and 2-amino-benzyl alcohol (20) with dicyclohexylcarbodiimide (DCC) in the presence of 1-hydroxy-benzotriazole afforded 2-fluoromethyl-3-(o-hydroxymethylphenyl)-6-nitro-4 (3H)-quinazolinone (21), which was converted to the metabolites 7 and 8. Treatment of the 2-bromomethyl-4 (3H)-quinazolinone (24) with AgBF4-H2O in dimethylsulfoxide (DMSO) gave the 2-hydroxymethyl metabolite 9. None of the main metabolites (2-9) showed significant central nervous system depressant activity

https://www.jstage.jst.go.jp/article/cpb1958/31/4/31_4_1158/_article

References

  1. Jump up^ US Patent 3966731 – 2-Fluoromethyl-3-o-tolyl-6-amino-4(3H)-quinazolinone
  2. Jump up^ Ochiai T, Ishida R. Pharmacological studies on 6-amino- 2-fluoromethyl- 3-(O-tolyl)- 4(3H)- quinazolinone (afloqualone), a new centrally acting muscle relaxant. (II) Effects on the spinal reflex potential and the rigidity. Japanese Journal of Pharmacology. 1982 Jun;32(3):427-38.
  3. Jump up^ Ishikawa T, Kamide R, Niimura M. Photoleukomelanodermatitis (Kobori) induced by afloqualone. Journal of Dermatology. 1994 Jun;21(6):430-3.
Afloqualone
Afloqualone.svg
Clinical data
AHFS/Drugs.com International Drug Names
ATC code
  • none
Legal status
Legal status
  • US: Unscheduled
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C16H14FN3O
Molar mass 283.3
3D model (JSmol)

//////////////Afloqualone, HQ 495, アフロクアロン , C033541, QA-3735, UNII:CO4U2C8ORZ, 4831

CC1=CC=CC=C1N2C(=NC3=C(C2=O)C=C(C=C3)N)CF

Afloqualone

    • ATC:M03A
  • Use:muscle relaxant
  • Chemical name:6-amino-2-(fluoromethyl)-3-(2-methylphenyl)-4(3H)-quinazolinone
  • Formula:C16H14FN3O
  • MW:283.31 g/mol
  • CAS-RN:56287-74-2
  • LD50:397 mg/kg (M, p.o.);
    249 mg/kg (R, p.o.)

Derivatives

hydrochloride

  • Formula:C16H14FN3O • xHCl
  • MW:unspecified
  • CAS-RN:56287-75-3

Substance Classes

Synthesis Path

Substances Referenced in Synthesis Path

CAS-RN Formula Chemical Name CAS Index Name
108-24-7 C4H6O3 acetic anhydride Acetic acid, anhydride
69123-71-3 C7H5ClN2O3 2-amino-5-nitrobenzoyl chloride Benzoyl chloride, 2-amino-5-nitro-
23076-31-5 C14H13N3O3 N-(2-amino-5-nitrobenzoyl)-o-toluidine Benzamide, 2-amino-N-(2-methylphenyl)-5-nitro-
56287-72-0 C16H14FN3O4 2-[(fluoroacetyl)amino]-N-(2-methylphenyl)-5-nitrobenzamide Benzamide, 2-[(fluoroacetyl)amino]-N-(2-methylphenyl)-5-nitro-
359-06-8 C2H2ClFO fluoroacetyl chloride Acetyl chloride, fluoro-
56287-73-1 C16H12FN3O3 2-(fluoromethyl)-3-(2-methylphenyl)-6-nitro-4(3H)-quinazolinone 4(3H)-Quinazolinone, 2-(fluoromethyl)-3-(2-methylphenyl)-6-nitro-
616-79-5 C7H6N2O4 5-nitroanthranilic acid Benzoic acid, 2-amino-5-nitro-
95-53-4 C7H9N o-toluidine Benzenamine, 2-methyl-

Trade Names

Country Trade Name Vendor Annotation
J Aflomus Hishiyama
Airomate SawaiNippon Chemiphar
Arofuto Tanabe

Formulations

  • tabl. 20 mg

References

    • Tani, J. et al.: J. Med. Chem. (JMCMAR) 22, 95 (1979).
    • DOS 2 449 113 (Tanabe; appl. 15.10.1974; J-prior. 15.10.1973).
    • US 3 966 731 (Tanabe; 29.6.1976; J-prior. 15.10.1973)
Title: Afloqualone
CAS Registry Number: 56287-74-2
CAS Name: 6-Amino-2-(fluoromethyl)-3-(2-methylphenyl)-4(3H)-quinazolinone
Additional Names: 6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone
Manufacturers’ Codes: HQ-495
Trademarks: Arofuto (Tanabe)
Molecular Formula: C16H14FN3O
Molecular Weight: 283.30
Percent Composition: C 67.83%, H 4.98%, F 6.71%, N 14.83%, O 5.65%
Literature References: A centrally acting muscle relaxant. Prepn: I. Inoue et al., DE 2449113eidem, US 3966731 (1975, 1976 to Tanabe); J. Tani et al., J. Med. Chem. 22, 95 (1979). Pharmacology: T. Ochiai, R. Ishida, Jpn. J. Pharmacol. 31, 491 (1981); 32,427 (1982). Metabolism: N. Otsuka et al., J. Pharmacobio-Dyn. 5, S-59 (1982); S. Furuuchi et al., Drug Metab. Dispos. 11, 371 (1983).
Properties: Pale yellow prisms from 2-propanol, mp 195-196°. LD50 in mice (mg/kg): 315.1 i.p. (Tani).
Melting point: mp 195-196°
Toxicity data: LD50 in mice (mg/kg): 315.1 i.p. (Tani)
Therap-Cat: Muscle relaxant (skeletal).
Keywords: Muscle Relaxant (Skeletal).
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DR ANTHONY CRASTO

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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