Ibuprofen: Structure,Synthesis,SAR,Mechanism,Uses

Ibuprofen

Structure –

Here is the chemical structure of ibuprofen:

Ibuprofen

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve pain, reduce fever, and decrease inflammation. The chemical name for ibuprofen is (±)-2-(4-isobutylphenyl)propanoic acid.

Synthesis –

The synthesis of ibuprofen involves the reaction of 2-methylpropene with benzene in the presence of a Lewis acid catalyst to form 4-isobutylacetophenone. The resulting ketone is then reacted with hydrogen peroxide and a mineral acid to form the corresponding phenylpropanoic acid. The final step involves resolution of the racemic mixture of the acid into its individual enantiomers using chiral resolving agents.

Here is a more detailed synthesis route:

  1. The reaction of 2-methylpropene with benzene in the presence of a Lewis acid catalyst such as aluminum chloride (AlCl3) or boron trifluoride (BF3) to form 4-isobutylacetophenone.

Ibuprofen

  1. The resulting ketone is then reacted with hydrogen peroxide (H2O2) and a mineral acid such as sulfuric acid (H2SO4) or phosphoric acid (H3PO4) to form the corresponding phenylpropanoic acid.
Ibuprofen
  1. The racemic mixture of the acid is then resolved into its individual enantiomers using chiral resolving agents such as (+)-tartaric acid or (-)-ephedrine.
Ibuprofen

The resulting enantiomers are then purified and used as the active ingredient in ibuprofen.

SAR –

The SAR (Structure-Activity Relationship) of Ibuprofen refers to the relationship between the chemical structure of ibuprofen and its biological activity, including its therapeutic effects and potential side effects.

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits the activity of the cyclooxygenase (COX) enzymes, particularly COX-2, which are responsible for the production of prostaglandins that cause pain, inflammation, and fever. The SAR of ibuprofen has been extensively studied to identify the structural features that are essential for its biological activity.

The key features of the SAR of ibuprofen are:

  1. Carboxylic acid group: The carboxylic acid group (-COOH) is essential for the biological activity of ibu-profen. It forms hydrogen bonds with the active site of COX-2 enzyme, which enhances the potency of the drug.
  2. Arylpropionic acid structure: The arylpropionic acid structure, which consists of an aromatic ring attached to a propionic acid moiety, is important for the binding of it to the COX-2 enzyme. The isobutyl group in the aryl ring contributes to the selective inhibition of COX-2 over COX-1.
  3. Chiral center: The chiral center in ibuprofen is located at the α-carbon atom adjacent to the carboxylic acid group. The S enantiomer of it is more active than the R enantiomer, as it has a higher affinity for the COX-2 enzyme.
  4. Lipophilic nature: The lipophilic nature of it is important for its absorption and distribution in the body. The isobutyl group in the aryl ring enhances the lipophilicity of ibuprofen, which allows it to penetrate cell membranes and reach its target site of action.

Overall, the SAR of it highlights the importance of the carboxylic acid group, arylpropionic acid structure, chiral center, and lipophilicity for its biological activity. Understanding the SAR of ibuprofen can help in the design and development of new NSAIDs with improved therapeutic efficacy and reduced side effects.

Mechanism –

The mechanism of it involves the inhibition of the activity of the cyclooxygenase (COX) enzymes, particularly COX-2, which are responsible for the production of prostaglandins that cause pain, inflammation, and fever. Ibuprofen is a non-selective COX inhibitor, which means that it inhibits both COX-1 and COX-2 enzymes, although it has a higher affinity for COX-2.

The mechanism of ibuprofen can be summarized as follows:

  1. it enters the body through oral administration and is absorbed in the gastrointestinal tract.
  2. it is distributed to the tissues and cells throughout the body, including the site of inflammation.
  3. Ibuprofen binds reversibly to the active site of the COX-2 enzyme, which is responsible for the production of prostaglandins in response to inflammation.
  4. By binding to COX-2, it prevents the conversion of arachidonic acid to prostaglandins, which reduces the production of inflammatory mediators.
  5. it also inhibits the activity of the COX-1 enzyme, which is involved in the production of prostaglandins that regulate homeostatic functions such as gastric mucosal protection, renal blood flow, and platelet aggregation.
  6. The inhibition of COX-1 by it can lead to side effects such as gastrointestinal ulcers, bleeding, and renal impairment.
  7. The therapeutic effects of it include the relief of pain, reduction of fever, and inhibition of inflammation.

In summary, the mechanism of it involves the inhibition of the COX enzymes, particularly COX-2, which reduces the production of prostaglandins and mediators of inflammation. However, the non-selective inhibition of COX-1 by ibuprofen can lead to potential side effects.

Uses –

it is a nonsteroidal anti-inflammatory drug (NSAID) that is commonly used for its analgesic (pain-relieving), antipyretic (fever-reducing), and anti-inflammatory effects. Some of the uses of ibuprofen include:

  1. Pain relief: it is often used to relieve mild to moderate pain, such as headache, dental pain, menstrual cramps, back pain, and musculoskeletal pain.
  2. Fever reduction: it can help reduce fever by lowering body temperature.
  3. Inflammatory conditions: it is used to reduce inflammation and swelling associated with conditions such as arthritis, tendonitis, bursitis, and other inflammatory conditions.
  4. Migraine: it is sometimes used to treat migraine headaches.
  5. Dysmenorrhea: it is commonly used to relieve pain associated with menstrual cramps.
  6. Post-operative pain: it may be used as part of a multimodal pain management strategy following surgery.
  7. Toothache: it  can help reduce pain associated with toothache.

It is important to note that ibuprofen is not appropriate for everyone and may have potential side effects and drug interactions. It is important to follow the dosage and usage instructions provided by a healthcare professional and to discuss any potential risks and benefits of ibuprofen use.

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