Tofacitinib

Product Name: Tofacitinib
CAS No.: 477600-75-2
Chemical Name: Tofacitinib
Synonyms: 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile;Tasocitinib;Tofacitinib base;Tofacitinib (CP-690550,Tasocitinib);Tofactinib;CS-344;CP 690550;Tofatinib;ofacitinib;Tofacitinb
CBNumber: CB0970901
Molecular Formula: C16H20N6O
Formula Weight: 312.38
MOL File: 477600-75-2.mol

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Tofacitinib Property

Density: 1.3
storage temp.: -20°C
solubility: Soluble in DMSO (up to 100 mg/ml) or in Ethanol (up to 100 mg/ml).
form: Pale powder.
pka: 6.04±0.60(Predicted)
color: Off-white
Stability:: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
InChI: InChI=1/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/s3
InChIKey: UJLAWZDWDVHWOW-BCFRMRSDNA-N
SMILES: N([C@@H]1[C@@H](CCN(C(=O)CC#N)C1)C)(C1N=CN=C2NC=CC=12)C |&1:1,2,r|
CAS DataBase Reference: 477600-75-2

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Safety

HS Code: 29335990
Hazardous Substances Data: 477600-75-2(Hazardous Substances Data)

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Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P273Avoid release to the environment.

P391Collect spillage. Hazardous to the aquatic environment

P501Dispose of contents/container to..…

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N-Bromosuccinimide Price

Usbiological

Product number: C7905-90
Product name: Tofacitinib
Packaging: 25mg
Price: $215
Updated: 2021/12/16

Biosynth Carbosynth

Product number: FT32555
Product name: Tofacitinib
Packaging: 500mg
Price: $225
Updated: 2021/12/16

Activate Scientific

Product number: AS17628-A
Product name: Tofacitinib
Purity: 98%
Packaging: 1g
Price: $250
Updated: 2021/12/16

Biosynth Carbosynth

Product number: FT32555
Product name: Tofacitinib
Packaging: 1g
Price: $300
Updated: 2021/12/16

ChemScene

Product number: CS-0050
Product name: Tofacitinib
Purity: 99.96%
Packaging: 1g
Price: $330
Updated: 2021/12/16

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Tofacitinib Chemical Properties,Usage,Production

Description

In November 2012, the US FDA approved tofacitinib (also referred to as CP-690550) for the treatment of adult patients with moderate to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. Tofacitinib is the first small molecule kinase inhibitor approved for the treatment of RA. Tofacitinib is an inhibitor of the four subtypes of Janus kinase (JAK): JAK1, JAK2, JAK3, and Tyk2. The JAKs are intracellular, nonreceptor tyrosine kinases that play important roles in the signal transduction pathway of many cytokines (e.g., interleukins 2, 4, 7, 9, 15, and 21) and are involved in the propagation of inflammation in RA. Tofacitinib acts by inhibiting the phosphorylation and activation of signal transducers and activators of transcription (STATs), thereby suppressing the production of inflammatory mediators in joint tissue. At the enzyme level, tofacitinib inhibits JAKs 1, 2, 3, and Tyk2 with IC_50s of 3.2, 4.1, 1.6, and 34 nM, respectively. At the cellular level, tofacitinib inhibits the in vitro activities of JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2 combinations with IC_50s of 406, 56, and 1377 nM, respectively.

Chemical Properties

Light Pink to Pale Orange Solid

Originator

Pfizer (United States)

Characteristics

Class: non-receptor tyrosine kinase
Treatment: RA, PA, JIA, UC
Oral bioavailability = 74%
Elimination half-life = 3.2 h
Protein binding = 40%

Uses

CP-690550 is a pyrrolo[2,3-d]pyrimidine derivative, as Janus kinase inhibitor for treatment of rheumatoid arthritis

Definition

ChEBI: A pyrrolopyrimidine that is pyrrolo[2,3-d]pyrimidine substituted at position 4 by an N-methyl,N-(1-cyanoacetyl-4-methylpiperidin-3-yl)amino moiety. Used as its citrate salt to treat moderately to severely ctive rheumatoid arthritis.

Indications

The JAK family includes four isoforms, JAK1, JAK2, JAK3, and tyrosine kinase (TYK2). Ruxolitinib (Jakafi(R), Incyte Corp.) was the first approved JAK inhibitor, which inhibits both JAK1 and JAK2, used for the treatment of different types of myelofibrosis. Tofacitinib (Xeljanz(R), Pfizer) was approved by FDA as a JAK3-selective inhibitor for the treatment of rheumatoid arthritis and is one of the only two FDA-approved kinase inhibitors for non-oncological indications.

brand name

Xeljanz

Pharmacokinetics

Tofacitinib has good solubility (>4 mg/mL in water for the crystalline citrate salt), which contributes to its excellent oral bioavailability (74%) in healthy volunteers. However, tofacitinib exhibits relatively short elimination half-life of 3.2 hours, and its protein binding is very low (approximately 40%, predominantly to albumin). Tofacitinib undergoes major hepatic clearance (70% of total clearance) and minor renal clearance (30%). The metabolism of tofacitinib proceeds primarily in the liver by CYP3A4 (major) and CYP2C19 (minor), resulting in oxidation of the pyrrolopyrimidine and piperidine rings, oxidation of the piperidine ring side-chain, N-demethylation, and glucuronidation. As opposed to the longer half-life of biologics, small-molecule JAK inhibitors such as tofacitinib typically display much shorter half-lives with once or twice-daily dosing regimens, which may be inconvenient to some patients. However, the shorter half-life ensures faster recovery to the full ability to fight infections which may occur with any immune suppressing medication.

Clinical Use

Tofacitinib was approved for treating rheumatoid arthritis in 2012, joint pain and swelling, psoriatic arthritis in 2017, and ulcerative colitis in 2018. However, severe side effects observed during clinical studies prevented the FDA from approving more efficacious doses for the treatment of rheumatoid arthritis (RA). Tofacitinib also carries a black box warning for an increased risk of pulmonary embolism and death associated with the 10 mg BID dose.

Synthesis

Commercially available aminopyridine 171 was reacted with dimethyl dicarbonate in the presence of potassium t-butoxide to give the methyl carbamate 172 in 87% yield. Hydrogenation of this carbamate 172 in the presence of 20 wt% of 5% Rh/C (JM type C101023-5) in acetic acid followed by reductive amination with benzaldehyde and sodium triacetoxy borohydride furnished the cis-benzyl protected piperidine 173 in 73% yield. Reduction of the methyl carbamate within 173 with lithium aluminum hydride (LAH) in THF gave the corresponding methyl amino piperidine which was isolated as the dihydrochloride salt 174 in 87% yield. Enantiomeric resolution of the methyl amino piperidine was achieved by freebasing the di-hydrochloride salt 174 with sodium hydroxide and then conversion to the di-toluol-L-tartaric acid salt followed by crystallization to give 175 in 42% yield and 98.6% ee. The enantioenriched tartrate salt 175 was then directly reacted with dichloride 176 (obtained from reaction of commercial 7H-pyrrolo[2,3-d]pyrimidine-2,4-diol (178) with phosphorous oxychloride) in the presence of potassium carbonate in water to give the coupled product 177 in essentially quantitative yield. Hydrogenation of intermediate 177 with DeGussa?ˉs catalyst triggered concomitant debenzylation and chloride removal, and this was followed by installation of the cyanoacetate group and subsequent treatment with citric acid to provide tofacitinib citrate (XXVII) in 90% yield.

References

1) Jiang et al. (2008), Examining the chirality, confirmation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitril (CP-690,550); J. Mol. Chem., 51 8012 2) Cutolo and Meroni (2013), Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis; J. Inflamm. Res., 6 129 3) Martina et al. (2016), Inhibition of JAK3 and PKC via Immunosuppressive Drugs Tofacitinib and Sotrastaurin Inhibits Proliferation of Human B Lymphocytes In Vitro; Transplant. Proc., 48 3046 4) Moisan et al. (2015), White-to-brown metabolic conversion of human adipocytes by JAK inhibition; Nat. Cell Biol., 17 57 5) Dowty et al. (2014), Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoid arthritis; J. Pharmacol. Exp. Ther., 348 165

Tofacitinib Preparation Products And Raw materials

Raw materials

Preparation Products

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Tofacitinib Suppliers

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View Lastest Price from Tofacitinib manufacturers

HangZhou RunYan Pharma Technology Co.,LTD.

Product: Tofacitinib 477600-75-2
Price: US $0.00-0.00/g
Min. Order: 10g
Purity: 99% HPLC
Supply Ability: 10000
Release date: 2024-09-10

Hebei Weibang Biotechnology Co., Ltd

Product: Tofacitinib 477600-75-2
Price: US $1.00/KG
Min. Order: 1KG
Purity: 99%
Supply Ability: 10 mt
Release date: 2024-11-18

Shaanxi Dideu New Materials Co. Ltd

Product: Tofacitinib 477600-75-2
Price: US $0.00-0.00/KG
Min. Order: 1KG
Purity: 98.0%
Supply Ability: 10000KGS
Release date: 2024-11-14

477600-75-2, TofacitinibRelated Search:

N-methyl-N-((3R,4R)-4-methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine Tofacitinib citrate N-((3R,4R)-1-benzyl-4-Methylpiperidin-3-yl)-2-chloro-N-Methyl-7H-pyrrolo[2,3-d]pyriMidin-4-aMine N-((3R,4R)-1-benzyl-4-Methylpiperidin-3-yl)-N-Methyl-7H-pyrrolo[2,3-d]pyriMidin-4-aMine 2-Pentenoic acid, 3-amino-2-cyano-5-[(3R,4R)-4-methyl-3-(methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1-piperidinyl]-5-oxo-, butyl ester 7H-Pyrrolo[2,3-d]pyrimidine-7-propanenitrile, 4-[[(3R,4R)-1-(2-cyanoacetyl)-4-methyl-3-piperidinyl]methylamino]-β-oxo- Nilotinib hydrochloride anhydrous GZD 824 Axitinib Cabozantinib Palbociclib Trametinib Dacomitinib (PF299804) Lenvatinib AZD 1480 Pictilisib Sunitinib Malate Ibrutinib

3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile

CP 690550

3-Piperidinamine, 1-(cyanoacetyl)-4-methyl-N-methyl-N-1H-pyrrolo(2,3-D)pyrimidin-4-yl-, (3R,4R)-

CP-690550(Tasocitinib,CP690550)

CP 690550(Tasocitinib)

Tasocitinib

3-((3R,4R)-4-Methyl-3-(Me...

Tasocitinib (CP 690550)

1-Piperidinepropanenitrile, 4-Methyl-3-(Methyl-7H-pyrrolo[2,3-d]pyriMidin-4-ylaMino)-β-oxo-, (3R,4R)-

1-Piperidinepropanenitrile, 4-Methyl-3-(Methyl-7H-pyrrolo[2,3-d]pyriMidin-4-ylaMino)-beta-oxo-, (3R,4R)-

Tofacitinib

CP-690550 Tofacitinib

3-((3R,4R)-4-Methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropa

Tofaimpurity

Tofacitinib base

Tofacitinib citrate, ≥98% (HPLC)

CP 690550 - Tasocitinib | Tofacitinib

3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile, Tofacitinib

3-{(3R,4R)-4-Methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-1-piperidinyl}-3-oxopropanenitrile

CS-344

CP690550 (Tofacitinib, Tasocitinib was stopped use)

Tofacitinib ?Tasocitinib

TOFACITINIB;TASOCITINIB;CP-690550;CP690550

Tofacitinib (CP-690550,Tasocitinib)

3-((3R,4R)-4-Methyl-3-(Methyl(7H-pyrrolo[2,3-d]pyriMidin-4-yl)aMino)-2-oxopiperidin-1-yl)propanenitrile

Tropsch iMatinib

CP 690550 3-((3R,4R)-4-Methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile

(3R,4R)-4-methyl-3-(methyl-1H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-β-oxo-1-piperidinepropanenitrile

Tofacitinib,CP-690550

Tofacitinib, >=98%

3-[4(R)-Methyl-3(R)-[N-methyl-N-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]- 3-oxopropanenitrile

(3R,4R)-4-methyl-3-(methyl-1H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-β-oxo-2-piperidinepropanenitrile

3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile(CP-690550)

ofacitinib

Tofactinib

Tofacitinib USP/EP/BP

CP-690550 DISCONTINUED

Tofacitinib 13C D2 15N

Tofacitinib 13C3Q: What is Tofacitinib 13C3 Q: What is the CAS Number of Tofacitinib 13C3 Q: What is the storage condition of Tofacitinib 13C3 Q: What are the applications of Tofacitinib 13C3

Tofacitinib D3Q: What is Tofacitinib D3 Q: What is the CAS Number of Tofacitinib D3

1-Piperidinepropanenitrile, 4-methyl-3-(methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-β-oxo-, (3R,4R)-

Dapagliflozin Impurity 148

Tofatinib

Tofacitinb

477600-75-2

Inhibitors

Inhibitor

API

477600-75-2

LFQ