53808-88-1

Usage

Uses

Used in Pharmaceutical Industry:
Lonazolac is used as a nonsteroidal anti-inflammatory drug (NSAID) for the management of mild to moderate pain, inflammation, and fever. It works by inhibiting the cyclooxygenase (COX) enzymes, which are responsible for the production of prostaglandins that cause pain, inflammation, and fever.
Additionally, lonazolac may be used as an analgesic for the relief of pain associated with various conditions such as headache, toothache, menstrual cramps, and musculoskeletal pain.
It may also be used as an antipyretic to reduce fever caused by infections or other inflammatory conditions.

Originator

Irriten,Tosse,W. Germany,1981

Manufacturing Process

17.6 g 1-phenyl-3-(p-chlorophenyl)-pyrazol-4-acetonitrile and 180 ml 25% aqueous hydrochloric acid were mixed and heated to the boiling temperature under reflux for 6 hours. To the mixture was then added dropwise concentrated aqueous sodium hydroxide until the pH of the mixture reached a value in the range from 3 to 5. The free pyrazol-4-acetic acid precipitated thereby was filtered off, redissolved in dilute aqueous sodium hydroxide, the solution cleared by treatment with activated carbon, and the pyrazol-4-acetic acid precipitated by acidifying the solution by the addition of dilute mineral acid, sulfuric acid. The filtered acid was crystallized from a mixture of ethanol and water. 17.1 g 1-phenyl-3-(p-chlorophenyl)pyrazol-4-acetic acid, melting at 148°C to 150°C, were obtained, representing a yield of 91%.

Therapeutic Function

Antiinflammatory

InChI:InChI=1/C17H13ClN2O2/c18-14-8-6-12(7-9-14)17-13(10-16(21)22)11-20(19-17)15-4-2-1-3-5-15/h1-9,11H,10H2,(H,21,22)/p-1

Upstream product

• 55432-07-0 1-phenyl-3-(p-chlorophenyl)-pyrazol-4-acetonitrile 
• 36640-39-8 4-hydroxy-methyl-1-phenyl-3-(p-chlorophenyl)-pyrazol 
• 36663-00-0 1-phenyl-3-(4-chlorophenyl)-4-pyrazolecarboxaldehyde 
• 2829-26-7 N-(4-chlorobenzylidene)-N'-phenylhydrazine 
• 55432-06-9 4-(chloromethyl)-3-(4-chlorophenyl)-1-phenyl-1H-pyrazole 

Downstream Products

• 1402041-61-5 2-(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-N-tosylacetamide 
• 1402041-65-9 2-[3-(1,1'-biphenyl-4-yl)-1-phenyl-1H-pyrazol-4-yl]-N-[(4-methylphenyl)sulfonyl]acetamide 
• 1402041-62-6 2-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-N-(methylsulfonyl)acetamide 
• 1402041-63-7 2-(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-N-(phenylsulfonyl)acetamide 
• 1402041-64-8 2-(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-N-(phenylsulfonyl)acetamide 

Relevant academic research and scientific papers

Synthesis of Pyrazoles Utilizing the Ambiphilic Reactivity of Hydrazones

A Br?nsted acid-mediated synthesis of pyrazoles from conjugated hydrazones through a β-protonation/nucleophilic addition/cyclization/aromatization sequence was developed. This protocol utilizing the ambiphilic reactivity of hydrazones enables not only self-condensation but also cross-condensation, affording multisubstituted pyrazoles in high yields, with a broad substrate scope. This sequential reaction proceeds under mild conditions via a simple operation. Moreover, the method can be applied to the synthesis of a nonsteroidal anti-inflammatory drug, Lonazolac.

A process for the preparation of 1-phenyl-3-(4-chlorophenyl)-pyrazol-4-ylacetic acid and its calcium salt

The invention relates to a process for preparing 1-phenyl--3-(4-chlorophenyl)-pyrazol-4-ylacetic acid, known under the generic name Lonazolac, and its calcium salt (Ca--Lonazolac). The process comprises the reductive hydrolysis of 1-phenyl-3-(4-chlorophenyl)-4-pyrazolecarboxaldehyde cyanohydrine using stannous chloride in a mixture of acetic acid, hydrochloric acid and preferably a catalytic amount of hydroiodic acid at elevated temperatures, and, if required, subsequent conversion of the acid into the calcium salt. The products are potent anti-inflammatory agents.

High molecular weight prodrug derivatives of antiinflammatory drugs

Compounds of the formula 1, PS - O - A - (CH2)n- B - D (1), wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyet-hyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan,A is a carbonyl group or absent,n is zero or a positive integer from 1 to 14,B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and, D is (i) a group of the formula:, R1 - CO - (11), wherein R1-CO- represents the acyl residue of a carboxylic acid drug (R1-COOH) used in the treatment of inflammatory disorders; or (ii) a group of the formula:, R2 - O - (12), wherein R2-O- refers to the C-21 alkoxide residue of a known antiinflammatory steroid (R2-OH) or an alkoxide residue of any other drug or medicament containing a hydroxy functional group used in the treatment of inflammatory disorders; with the proviso that when A is absent, n is 0, and B is absent, then R1-CO- is different from the acyl residue of acetylsalicylic acid;, and non-toxic pharmaceutically acceptable acid addition salts thereof;, and non-toxic pharmaceutically acceptable cation salts thereof. Such compounds are biolabile prodrugs providing controlled release and prolonged duration of action of the parent active antiinflamma-tory agents locally at the administration site after intra-articular, intra-muscular, subcutaneous or extra-dural application while at the same time being highly stable in aqueous solution in the pH range 3--5. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time.

Synthesis and physico-chemical properties of lonazolac-Ca, a new anti-inflammatory/antirheumatic agent

Calcium-[3-(p-chlorophenyl)-1-phenylpyrazole-4]-acetate (Lonazolac-Ca, active principle of Irritren) is a new anti-inflammatory/antirheumatic agent whose synthesis and physico-chemical properties are described. The physical parameters measured (pKa, partition coefficient P, saturation concentration c(s), surface activity, protein binding) are held against the corresponding values of indometacin, diclofenac, and phenylbutazone. The size of the permeability coefficient P(m) of the passive transport through artificial phospholipid collodion membranens as well as the invasion curves calculated from P(m) indicate a good absorption of lonazolac in man.

Pyrazol-4-acetic acid compounds

Pyrazol-4-acetic acid compounds, such as substituted pyrazol-4-acetic acid, its esters, amides, nitriles and their pharamaceutically acceptable salts and method for the preparation of these compounds are disclosed. The novel compounds are useful analgesics, anti-inflammatory, and antipyretics.