Tofacitinib

Tofacitinib Properties

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
FDA UNII	87LA6FU830
NCI Drug Dictionary	tofacitinib
ATC code	L04AA29

SAFETY

Risk and Safety Statements

Symbol(GHS)	GHS09
Signal word	Warning
Hazard statements	H410
Precautionary statements	P501-P273-P391
HS Code	29335990

Tofacitinib price

Manufacturer	Product number	Product description	CAS number	Packaging	Price	Updated	Buy
Usbiological	C7905-90	Tofacitinib	477600-75-2	25mg	$215	2021-12-16	Buy
Biosynth Carbosynth	FT32555	Tofacitinib	477600-75-2	500mg	$225	2021-12-16	Buy
Activate Scientific	AS17628-A	Tofacitinib 98%	477600-75-2	1g	$250	2021-12-16	Buy
Biosynth Carbosynth	FT32555	Tofacitinib	477600-75-2	1g	$300	2021-12-16	Buy
ChemScene	CS-0050	Tofacitinib 99.96%	477600-75-2	1g	$330	2021-12-16	Buy

Product number	Packaging	Price	Buy
C7905-90	25mg	$215	Buy
FT32555	500mg	$225	Buy
AS17628-A	1g	$250	Buy
FT32555	1g	$300	Buy
CS-0050	1g	$330	Buy

Tofacitinib Chemical Properties,Uses,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

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.

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.

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.

Synthesis_477600-75-2

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

Tofacitinib Suppliers

Global( 471)Suppliers

Supplier	Tel	Email	Country	ProdList	Advantage
Changsha Junyu Chemexpress.co., Ltd	+86-13723890100	info@csjyyy.cn	China	134	58
Changzhou Rokechem Technology Co., Ltd.	18758118018	sales001@rokechem.com	China	255	58
Senova Technology Co. Ltd.	+86-0755-86703119 +8618503098836	info@senovatech.com	China	351	58
HangZhou RunYan Pharma Technology Co.,LTD.	+8618882027439	sales2@runyanpharma.com	China	302	58
Hebei Weibang Biotechnology Co., Ltd	+8615531157085	abby@weibangbio.com	China	8812	58
Hebei Mojin Biotechnology Co., Ltd	+86 13288715578 +8613288715578	sales@hbmojin.com	China	12840	58
Henan Fengda Chemical Co., Ltd	+86-371-86557731 +86-13613820652	info@fdachem.com	China	20287	58
Hebei Mojin Biotechnology Co.,Ltd	+86-15028179902	angelia@hbmojin.com	China	1177	58
Cangzhou Kangrui Pharma Tech Co. Ltd.,	+86-18632776803 +86-13833998158	cangzhoukangrui@126.com	China	736	58
Capot Chemical Co.,Ltd.	+86-（0）57185586718 +86-13336195806	sales@capot.com	China	29791	60

Supplier	Advantage
Changsha Junyu Chemexpress.co., Ltd	58
Changzhou Rokechem Technology Co., Ltd.	58
Senova Technology Co. Ltd.	58
HangZhou RunYan Pharma Technology Co.,LTD.	58
Hebei Weibang Biotechnology Co., Ltd	58
Hebei Mojin Biotechnology Co., Ltd	58
Henan Fengda Chemical Co., Ltd	58
Hebei Mojin Biotechnology Co.,Ltd	58
Cangzhou Kangrui Pharma Tech Co. Ltd.,	58
Capot Chemical Co.,Ltd.	60

View Lastest Price from Tofacitinib manufacturers

Update time	Product	Price	Min. Order	Purity	Supply Ability	Manufacturer
2024-11-22	Tofacitinib 477600-75-2	US $0.00-0.00 / g	10g	99% HPLC	10000	HangZhou RunYan Pharma Technology Co.,LTD.
2024-11-19	Tofacitinib 477600-75-2	US $30.00-59.00 / mg		99.71%	10g	TargetMol Chemicals Inc.
2024-11-18	Tofacitinib 477600-75-2	US $1.00 / KG	1KG	99%	10 mt	Hebei Weibang Biotechnology Co., Ltd

Tofacitinib
477600-75-2
US $0.00-0.00 / g
99% HPLC
HangZhou RunYan Pharma Technology Co.,LTD.

Tofacitinib
477600-75-2
US $30.00-59.00 / mg
99.71%
TargetMol Chemicals Inc.

Tofacitinib
477600-75-2
US $1.00 / KG
99%
Hebei Weibang Biotechnology Co., Ltd

Tofacitinib Spectrum

Tofacitinib(477600-75-2)MS

477600-75-2(Tofacitinib)Related 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

1of4

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) 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) 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 ofacitinib 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 Tofaimpurity 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 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile Tasocitinib Tofacitinib (CP-690550,Tasocitinib) Tofactinib Tofacitinib base 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