Shaanxi BLOOM Tech Co., Ltd. is one of the most experienced manufacturers and suppliers of upadacitinib powder cas 1310726-60-3 in China. Welcome to wholesale bulk high quality upadacitinib powder cas 1310726-60-3 for sale here from our factory. Good service and reasonable price are available.
Upadacitinib powder is a white to off-white solid with an odorless, slightly bitter taste. The molecular formula is C17H19N7O and the molecular weight is 323.38 g/mol. The compound mainly consists of a pyridine ring, a pyrimidine ring and a piperidine ring. Wherein, there is a methyl group and an amino group on the piperidine ring, and a methylthiol group is connected to the pyrimidine ring. At the same time, it also contains a carboxamide group, which is the mechanism basis for its ability to selectively inhibit the effects of JAK1 on JAK2, JAK3 and TYK2. The solubility in acidic medium with pH 1.2 is less than 0.1 mg/mL, while the solubility in buffer solution with pH 6.8 is as high as 21 mg/mL.
|
|
|
Also, it has low solubility in water. is an oral, selective JAK (Janus kinase) inhibitor used as a treatment for rheumatoid arthritis and other autoimmune diseases. It is an oral selective JAK inhibitor whose main component is a compound containing carboxamide group and pyridine ring, pyrimidine ring and piperidine ring. The drug has good pharmacokinetic properties and stability, and has an important therapeutic effect on rheumatoid arthritis and other autoimmune diseases.
Upadacitinib powder as a next-generation selective Janus kinase (JAK) inhibitor, mainly inhibits JAK1 enzyme activity by targeting and blocking the intracellular JAK-STAT signaling pathway, thereby suppressing the release of inflammatory factors and overactivation of the immune system. Based on its unique mechanism of action, Upatinib has shown significant efficacy in the treatment of various autoimmune and inflammatory diseases.
Core mechanism: Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation of the joint synovium, and JAK1 mediated signaling pathways of pro-inflammatory cytokines such as IL-6 and IL-2 play a key role in disease progression. By selectively inhibiting JAK1, blocking these signaling pathways, reducing synovitis and bone destruction.
Clinical evidence:
SELECT-COMPARE study: In moderate to severe RA patients with insufficient response to methotrexate (MTX), after 12 weeks of treatment with Upatinib (15mg/day) combined with MTX, the ACR20 (American College of Rheumatology Improvement Criteria) response rate reached 71%, significantly higher than Adalimumab (59%) and placebo (36%);
At 24 weeks, the DAS28-CRP (Disease Activity Score) remission rate reached 29%, which was better than Adalimumab (18%).
Long term efficacy: The SELECT-BEYOND study showed that after 5 years of treatment with Upatinib, 75% of patients who failed with biologics maintained low disease activity (LDA), 50% achieved clinical remission, and the progression of X-ray bone erosion was significantly inhibited.
Core mechanism: Psoriatic arthritis is characterized by joint inflammation and skin psoriasis, and the JAK1 mediated IL-23/IL-17 axis and IL-6 signaling pathway are involved in the disease pathogenesis. By inhibiting JAK1, joint synovial hyperplasia and skin inflammation can be reduced.
Clinical evidence:
SELECT-PsA 1/2 study: After 16 weeks of treatment with Upatinib (15mg/day), 60% -65% of patients achieved an improvement of ≥ 75% in the area and severity index (EASI-75) of psoriasis, significantly better than placebo (10% -15%);
The improvement rate of joint symptoms (ACR20) reached 57% -62%, which was better than placebo (24% -31%).
Structural Protection: SELECT-PsA 2 study showed that after 24 weeks of treatment with Upatinib, the progression of joint structural damage (mTSS score) was reduced by 67% compared to placebo.
Core mechanism: Ankylosing spondylitis is characterized by axial joint inflammation and osteophyte formation, and the JAK1 mediated IL-17 and TNF signaling pathways drive disease progression. Upatinib reduces spinal inflammation and bone formation by inhibiting JAK1.
Clinical evidence:
SELECT-AXIS 1 study: In active AS patients, after 14 weeks of treatment with Upatinib (15mg/day), the ASAS40 (International Association for the Evaluation of Spinal Arthritis Improvement Criteria) response rate reached 52%, significantly higher than placebo (26%);
After 16 weeks of treatment, the patient's spinal range of motion (BASMI score) improved more significantly than placebo.
Indications for nr axSpA: Based on a similar mechanism, Upatinib is approved for active nr axSpA in adult patients with insufficient response to nonsteroidal anti-inflammatory drugs (NSAIDs).
Core mechanism: Upadacitinib powder is characterized by skin barrier dysfunction and Th2 type immune response, with JAK1 mediated cytokine signaling pathways such as IL-4 and IL-13 driving skin inflammation. By inhibiting JAK1, reduce skin itching and erythema.
Clinical evidence:
Measure Up 1/2 study: In adolescents and adults with moderate to severe AD, 60% -65% of patients treated with Upatinib (15mg/day) achieved EASI-75 after 16 weeks, while the 30mg/day group achieved 70% -75%, significantly better than placebo (10% -15%);
The proportion of patients with an improvement of ≥ 4 points on the Itch Digital Rating Scale (NRS) was 58% -63%, which was better than placebo (14% -18%).
Long term control: The AD Up study showed that after 52 weeks of combined topical corticosteroid treatment, 70% of patients maintained EASI-75 response, and the incidence of serious adverse events was not significantly different from the placebo group.
Core mechanism: Inflammatory bowel disease (IBD) is characterized by immune imbalance of the intestinal mucosa, driven by JAK1 mediated cytokine signaling pathways such as IL-6, IL-12/IL-23, which drive intestinal inflammation. Reduce intestinal ulcers and diarrhea by inhibiting JAK1.
Clinical evidence:
U-ACHIEVE study (UC): After 8 weeks of treatment with Upatinib (45mg/day induction, 15-30mg/day maintenance), the clinical remission rate reached 26%, significantly higher than placebo (5%); During the 52 week maintenance treatment period, 70% of patients maintained hormone free remission.
Indications for CD: Based on a similar mechanism, approved for use in adult patients with moderate to severe active CD who have insufficient response or intolerance to TNF inhibitors.
Potential indication: Non segmental vitiligo (NSV)
Core mechanism: Vitiligo is characterized by the absence of skin pigment cells, and the JAK1 mediated interferon (IFN) - γ signaling pathway drives the destruction of pigment cells. By inhibiting JAK1, reducing pigment cell apoptosis and promoting repigmentation.
Clinical evidence:
Viti Up study: In adult and adolescent NSV patients, the proportion of patients with facial pigment regeneration area increased by ≥ 50% compared to baseline after 24 weeks of treatment with Upatinib (15mg/day) was 45%, significantly better than placebo (12%);
The improvement in total body pigment regeneration score (T-VASI) was more significant than that of placebo.
Regulatory progress: In 2026, NSV indication applications have been submitted to the US FDA and European EMA. If approved, it will become the first systemic vitiligo treatment drug.
Upatinib has become a core therapeutic drug for various autoimmune and inflammatory diseases by selectively inhibiting JAK1 and accurately blocking multiple inflammatory signaling pathways. Its indications cover rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, atopic dermatitis, ulcerative colitis, Crohn's disease, and are expected to expand to the field of vitiligo.
The following is a brief overview of the upadacitinib powder synthesis method, which is mainly divided into the following steps:
1. Introduction of pyridine ring:
The synthesis of Upadacitinib begins with the reaction of 4-Amino-3-methylbenzoic acid methyl ester with 2-chloropyridine to generate 4-[(2-chloropyridin -3-yl)methoxy]-3-methylbenzamide.
2. Construction of the pyrimidine ring:
Next, using nucleophilic aromatic substitution reaction (SNAr), 4-[[4-[(2-chloropyridin-3-yl)methoxy]-3-methylphenyl]amino]-2-methylthiopyrimidine-5-carbonitrile was used as raw material, After a multi-step reaction, the precursor compound 4-[[4-(3H-imidazo[1,2-b]pyrazin-6-yl)methoxy]-3-methylphenyl]amino]-2-methylthiopyrimidine-5 of Upadacitinib was synthesized -carbonitrile.
3. Introduction of piperidine ring:
4-[[4-(3H-Imidazo[1,2-b]pyrazin-6-yl)methoxy]-3-methylphenyl]amino]-2-methylthiopyrimidine-5-carbonitrile was treated with hydroxylamine to form a piperidine ring . This step usually requires a certain reaction time and temperature.
4. Introduction of carboxylic acid:
Finally, the methylthiol group on the pyrimidine ring of Upadacitinib was converted into a carboxylic acid by esterification reaction with diethyl carbonate (Diethyl carbonate) and acetyl chloride (Acetyl chloride), to obtain the full synthesis of Upadacitinib.
In addition to the methods described above, Mohamed et al. also mentioned some other upadacitinib synthesis methods in the literature, such as the method of directly reacting phosphorus trichloride (Phosphorous trichloride) and 2-chloropyridine to obtain a pyridine ring, using different raw materials To construct the pyrimidine ring and so on. These methods are all able to successfully obtain Upadacitinib, but their synthetic routes may be slightly different. In addition, different laboratories may have different synthesis methods, so the synthesis method of Upadacitinib is not unique.
|
Chemical Formula |
C17H19F3N6O |
|
Exact Mass |
380 |
|
Molecular Weight |
380 |
|
m/z |
380 (100.0%), 381 (18.4%), 381 (2.2%), 382 (1.6%) |
|
Elemental Analysis |
C, 53.68; H, 5.04; F, 14.98; N, 22.09; O, 4.21 |
Upadacitinib has a solubility of less than 0.1 mg/mL in acidic media at pH 1.2 and a solubility of up to 21 mg/mL in buffered solutions at pH 6.8. Also, it has low solubility in water. These data suggest that upadacitinib is more soluble in neutral or alkaline environments and is more stable relative to acidic environments.
According to relevant research, Upadacitinib is stable at room temperature, and it will not lose its efficacy even if it is frozen at -20°C for a long time. Additionally, the drug can be stabilized in conventional compressed tablet, capsule or solution dosage forms. These data indicate that Upadacitinib has good chemical stability among common drug types.
Upadacitinib is a white to off-white solid with an odorless, slightly bitter taste. Its elemental state is a colorless and transparent crystal. These properties can also be used to analyze the purity of Upadacitinib.
As an oral drug, Upadacitinib usually requires metabolic reactions in the human body to exert its therapeutic effect. Studies have shown that after upadacitinib is metabolized by CYP3A4, it will generate a metabolite M12. The structure of M12 is similar to that of Upadacitinib, so it also has certain anti-inflammatory effects. Other studies have also shown that Upadacitinib may be hydrolyzed into smaller molecules through the action of carboxylesterase in the human body. These data indicate that Upadacitinib has a relatively complex metabolic pathway in the human body.
Overall, Upadacitinib is an oral, selective JAK inhibitor with relatively stable chemical properties. It is mainly composed of a compound containing a carboxamide group and a pyridine ring, a pyrimidine ring and a piperidine ring, and can selectively inhibit the effect of JAK1 on JAK2, JAK3 and TYK2. Although upadacitinib powder has certain metabolic reactions in the human body, it still has good pharmacokinetic properties and stability.
FAQ
What is upadacitinib used for?
Upadacitinib is used to treat moderate to severe active rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis (a type of arthritis in the spine) with objective signs of swelling, and polyarticular juvenile idiopathic arthritis (PJIA) in patients who have used ...
Is upadacitinib approved in China?
Upadacitinib (UPA) is the 1st oral, reversible, selective Janus kinase inhibitor that approved in China for moderately to severely active Crohn's disease (CD) treatment.
Is upadacitinib a JAK inhibitor?
Upadacitinib is a selective Janus kinase (JAK) inhibitor which is approved by the US Food and Drug Administration, the European Medicines Agency, as well as other agencies around the world for the treatment of several chronic inflammatory diseases, including rheumatic, dermatologic, and gastrointestinal diseases.
Upadacitinib: Mechanism of action, clinical, and translational science
Is upadacitinib an immunosuppressant?
Upadacitinib belongs to a group of medicines called janus kinase (JAK) inhibitors. It works by blocking a substance in your body called janus kinase, thought to cause inflammation. Upadacitinib is an immunosuppressive medicine, which helps to calm an overactive immune response.
Hot Tags: upadacitinib powder cas 1310726-60-3, suppliers, manufacturers, factory, wholesale, buy, price, bulk, for sale, 6 methylergoline 8beta carboxylic Acid CAS 5878 43 3, pontocaine, Clascoterone Powder CAS 19608 29 8, iptg powder, Organic Intermediate, 4 BROMO 1 BUTYNE CAS 38771 21 0