English name: Thalidomide

CAS: 50-35-1

EINECS: 200-031-1

Molecular formula: C13H10N2O4

MDL: MFCD00153873

Molecular weight: 258.23

Development course

Thalidomide is a synthetic glutamic acid derivative, commonly known as thalidomide, thalidomide, Thalidomide, thalidomide, thalidomide, thalidomide, thalidomide, thalidomide, at room temperature is a white crystalline powder, odorless, tasteless, slightly soluble in water, methanol, ethanol or acetone, easily soluble in dimethylformamide or pyridine, insoluble in ether, chloroform or benzene.

In the 1950s, the drug was developed by Germany to treat epilepsy, but due to a lack of effectiveness, it was subsequently used as a sleep aid, while widely used during pregnancy to stop vomiting in pregnant women.

In the early 1960s, the thalidomide event - a large number of thalidomide induced infant deformity reports (e.g. Short limb deformity, long bone defect, loss of auriculae, cleft lip, heart and gastrointestinal deformity, etc.), which was banned by many countries and withdrawn from the medical market, but scientists did not completely deny thalidomide, continue to conduct in-depth research on it. Especially in the immune, anti-inflammatory, anti-angiogenesis pharmacology and some difficult diseases on the clinical treatment of the research has achieved gratifying and encouraging results, so that people have a new understanding of thalidomide.

Since the 1970s, with the development of research on leprosy, rheumatism and various types of malignant tumors, thalidomide has been used by Israel Dermatology as a sedative in patients with erythema leprosum, and symptoms have improved rapidly. After many cases of lepromatous erythema nodosum patients with the use of response have obtained a good therapeutic effect, in 1998 the United States FDA approved thalidomide for the treatment of lepromatous erythema nodosum.

At the annual meeting of the American Society of Hematology in 2004, RaJkumar of Mayo Hospital in the United States reported the results of two studies on the first-line treatment of multiple myeloma with thalidomide and its analogue (lenalidomide). Both thalidomide and its analogue lenalidomide can effectively treat multiple myeloma. lenalidomide is more effective than thalidomide.

In May 2006, the US FDA approved it for the treatment of multiple myeloma.

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Foreign scholars reported that 7 patients with rheumatoid diseases who were ineffective with multiple anti-inflammatory drugs and immunosuppression were treated with thalidomide, and most of the results were alleviated within a few weeks, and the dose was 400-600 mg/d. The ESR and rheumatoid factor titers of all patients were normalized or significantly decreased, and the rheumatoid nodules of 1 case disappeared at 12 weeks. Seven patients with refractory rheumatoid disease were treated with a combination of thalidomide and methotrexate, and 4 of the 5 patients who persisted in treatment improved joint tenderness and reduced joint swelling within 3 to 9 months.

Thalidomide can treat the following diseases:

1. Behcet's disease.

2. Systemic lupus erythematosus.

3. Rheumatoid arthritis.

4. Erythema nodosum, Crohn's disease.

5. Scleroderma: Gastroesophageal reflux symptoms, healing of duodenal ulcer and hypopigmentation can be significantly improved within 12 weeks after the start of treatment.

6. Adults are Still sick.

7. Refractory ankylosing spondylitis, multiple myeloma (MM).

The clinical treatment of rheumatism starts with a small dose, 25-50mg/day per night, and gradually increases to 100-200mg/day, with the maximum dose not exceeding 400mg/ day.

Adverse reaction

The main adverse reactions during thalidomide treatment include drowsiness, dizziness, drowsiness, headache, constipation, nausea, vomiting, dry mouth, dry skin, erythema and papulovesicular transient rash, but none of them are serious and will disappear after termination of administration.

The adverse effects that should be noted are polyneuritis, the main symptoms are loss of surface or deep sensation and muscle weakness, the appearance of symptoms is disproportionate to the dose and course of treatment, the time of onset of symptoms is also very different, and in cases where treatment is not terminated, this symptom is irreversible. In addition, there are low white blood cells, abnormal liver function, and well-known malformation effects. Other rare side effects include bradycardia, edema, abnormal blood clotting, renal failure, pneumonia, paraesthesia, and hypothyroidism.

Synthesis method

Step 1: Preparation of thalidomide crude

Put 10kgN phthalate glutamic anhydride into the reactor, heat to melt, and pass ammonia gas. After the reaction is complete, the reaction liquid is placed in water and stirred at the same time. After cooling, filter and wash the cake with water to obtain 10kg crude thalidomide.

Step 2: Preparation of high purity thalidomide

100g of thalidomide crude product (97.3% by HPLC) was added with 200g dimethyl sulfolone and 1g activated carbon, and dissolved at 100℃. The filtrate was cooled to 0℃ while hot, and the filtrate was filtered, washed with ethanol, and dried at 80℃ to obtain 65g thalidomide.

Biological activity

Thalidomide acts as a sedative, immunomodulator and is also used in research to treat the symptoms of many cancers. Thalidomide inhibits E3 ubiquitin ligase (a CRBN-DDB1-Cul4A complex).