1,14-Dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone

Base Information Edit

Chemical Name:1,14-Dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone
CAS No.:104987-11-3
Molecular Formula:C44H69NO12
Molecular Weight:804.031
Hs Code.:29349990
European Community (EC) Number:627-021-3,658-056-2
Wikipedia:Tacrolimus
Wikidata:Q105222713
Mol file:104987-11-3.mol

1,14-Dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone

Synonyms:104987-11-3;1,14-dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone;144490-63-1;MFCD00869853;129212-35-7;QJJXYPPXXYFBGM-UHFFFAOYSA-N;SY069910;FT-0626431;17-allyl- 1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone;17-allyl-1,14-di-hydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9] octacos-18-ene-2,3,10,16-tetraone;17-Allyl-1,14-di-hydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone;17-allyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxy -cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone;17-allyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,-27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone;17-allyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone;17-allyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]-octacos-18-ene-2,3,10,16-tetraone

Suppliers and Price of 1,14-Dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone

Supply Marketing:Edit

Business phase:: The product has achieved commercial mass production^*data from LookChem market partment

Manufacturers and distributors:

Manufacture/Brand
Chemicals and raw materials
Packaging
price

TRC
FK-506(Tacrolimus)
100mg
$ 165.00

Sigma-Aldrich
Tacrolimus United States Pharmacopeia (USP) Reference Standard
150 mg
$ 1730.00

Sigma-Aldrich
Tacrolimus solution 1.0?mg/mL in acetonitrile, ampule of 1?mL, certified reference material, Cerilliant?
1 mL
$ 203.00

Sigma-Aldrich
Tacrolimus Pharmaceutical Secondary Standard; Certified Reference Material
150 mg
$ 396.00

Sigma-Aldrich
Tacrolimus solution 1.0mg/mL in acetonitrile, ampule of 1mL, certified reference material
049-1ml
$ 197.00

Sigma-Aldrich
Tacrolimus solution Immunosuppressant that blocks T cell proliferation
5mg
$ 175.00

Frontier Specialty Chemicals
Tacrolimus
10mg
$ 124.00

Frontier Specialty Chemicals
Tacrolimus
50mg
$ 413.00

DC Chemicals
FK-506(Tacrolimus) 99%
250 mg
$ 250.00

DC Chemicals
FK-506(Tacrolimus) 99%
100 mg
$ 150.00

Total 259 raw suppliers

Chemical Property of 1,14-Dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone Edit

Chemical Property:

Appearance/Colour:White or off-white crystalline powder
Vapor Pressure:1.73E-35mmHg at 25°C
Melting Point:113-115 °C
Refractive Index:1.549
Boiling Point:871.7 °C at 760 mmHg
PKA:9.97±0.70(Predicted)
Flash Point:481 °C
PSA：178.36000
Density:1.19 g/cm³
LogP:4.57690
Storage Temp.:−20°C
Solubility.:DMSO: >3 mg/mL
Water Solubility.:Freely soluble in DMSO or ethanol. Poorly soluble in water.Soluble in dimethyl sulfoxide, ethanol, water, acetone, chloroform, e
XLogP3:2.7
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:12
Rotatable Bond Count:7
Exact Mass:803.48197664
Heavy Atom Count:57
Complexity:1480

Purity/Quality:

99%min ^*data from raw suppliers

FK-506(Tacrolimus) ^*data from reagent suppliers

Safty Information:

Pictogram(s): T,Xi
Hazard Codes:T,Xi,Xn,F
Statements: 25-36/37/38-36-20/21/22-11
Safety Statements: 45-36-26-36/37-16-60-20

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

Canonical SMILES:CC1CC(C2C(CC(C(O2)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C(CC(=O)C(C=C(C1)C)CC=C)O)C)C(=CC4CCC(C(C4)OC)O)C)O)C)OC)OC
Recent EU Clinical Trials:Phase-I/II trial to assess the safety and efficacy of Venetoclax in addition to sequential conditioning with Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for allogeneic blood stem cell transplantation in patients with MDS, CMML or sAML (FLAMSAClax)
Description FK-506 is a potent immunosuppressant in the same molecular class as cyclosporin A and rapamycin . Its mechanism of action involves the formation of a high affinity complex (Ki = 0.2 nM) with FK-506 binding protein 12 (FKBP12). This complex then inhibits the activity of the calcium/calmodulin-dependent protein phosphatase, calcineurin, leading to disruption of T cell activation. The physiological effects of FK-506 also include regulation of nitric oxide neurotoxicity, neurotransmitter release, and regulation of Ca2+ release via the ryanodine and inositol-(1,4,5)-trisphosphate (IP3) receptors. In the latter case, FKBP12 forms a tight complex with both ryanodine and IP3 receptors which can be disrupted by FK-506, thereby rendering the receptors leaky to Ca2+. Tacrolimus, isolated from the microorganism Streptomyces tsukubaensis, is a macrolide immunosuppressant developed by Fujisawa for organ transplantation. It displays similar but more potent immunosuppressive activity than cyclosporin. It inhibits both cell mediated and humoral immune responses. In animal models of organ transplantation, tacrolimus has been shown to prolong survival of hepatic, renal, cardiac, small intestine, pancreatic and skin allografts and to reverse cardiac and renal allograft rejection. It has been used effectively in humans as rescue or primary immunosuppressant therapy in liver or kidney transplantation. Compared to cyclosporin, tacrolimus causes reduced incidence of infectious complications and of hypertension and hypercholesterolemia for the allograft recipients. In common with cyclosporin, tacrolimus binds with high affinity to a family of cytoplasmic immunosuppressant binding proteins, the immunophilins. This tight complex is proposed as the biologically active moiety that interacts with intracellular molecules involved in signal transduction.It inhibits phosphatase activity of calcineurin, an action that may impair the generation and/or activation of nuclear transcription factors required for lymphokine (particularly interleukin-2) gene expression. Tacrolimus has also been reported to have potential in multiple sclerosis, psoriasis, rheumatoid arthritis and uveitis associated with Behcet‘s disease.
Uses An immunosuppressant that blocks T cell proliferation in vitro by inhibiting the generation of several lymphokines, especially IL-2. Shown to inhibit the activity of FK-506 binding protein, thereby reversing its effects on sarcoplasmic reticulum Ca+2 release. FK-506 (Tacrolimus) is a macrolide immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system Tacrolimus (fujimycin) was discovered as a potent inhibitor of IL2 production in a targeted search for novel immunosuppressants. Tacrolimus acts by blocking T cell proliferation in vitro by inhibiting the generation of several lymphokines, notably the original target IL-2. Tacrolimus inhibits the activity of FK-506 binding protein, Ca2+-dependent phosphatase and calcineurin, and activates NF-κB through phosphorylation and degradation of IκBα. treatment of Cushing's syndrome For use after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It was first approved by the FDA in 1994 for use in liver transplantation, this has been extended to include kidney, heart,
Indications Tacrolimus is a macrolide lactone originally derived from Streptomyces tsukubaensis. Although structurally unrelated to cyclosporine, tacrolimus has a very similar mechanism of action; that is, it blocks the production of proinflammatory cytokines by T lymphocytes by inhibiting calcineurin.Tacrolimus, however, appears to be 10 to 100 times as potent as an immunosuppressive. Oral tacrolimus (FK506) is used for prevention of organ rejection in recipients of renal and hepatic transplants. Tacrolimus (Prograf) is a second-generation immunosuppressive agent that has been approved for use in liver transplantation. Its efficacy for other transplantations is being evaluated. It has properties similar to those of cyclosporine except that weight for weight it is 10 to 100 times more potent. It is a macrolide antibiotic that selectively inhibits transcription of a specific set of lymphokine genes in T lymphocytes (e.g., IL-2, IL-4, and interferon-) and binds to cytoplasmic proteins in lymphocytes. Although the binding proteins (cytophilins) for cyclosporine and tacrolimus are different, they share similar functions in that the cytophilins are important for the intracellular folding of proteins. It is speculated that these proteins are important in regulating gene expression in T lymphocytes and that both drugs somehow interfere in this process. Absorption of tacrolimus from the gastrointestinal (GI) tract is variable. It is extensively metabolized in the liver and excreted in the urine.As with cyclosporine, nephrotoxicity is its principal side effect.
Therapeutic Function Immunosuppressive
Clinical Use A topical formulation (Protopic) has recently been approved for treatment of moderate to severe atopic dermatitis in children and adults who have not responded to other therapies. Levels of systemic absorption are low even when applied to a relatively large body surface area.
Drug interactions Potentially hazardous interactions with other drugs Ciclosporin: may increase the half-life of ciclosporin and exacerbate any toxic effects. The two should not be prescribed concomitantly. Care should be taken when converting from ciclosporin to tacrolimus. Tacrolimus levels increased by: amlodipine, atazanavir, basiliximab, boceprevir, bromocriptine, chloramphenicol, cimetidine, cortisone, danazol, dapsone, diltiazem, ergotamine, ethinyloestradiol, felodipine, fosamprenavir, gestodene, grapefruit juice, imidazole and triazole antifungals, lidocaine, lansoprazole, possibly levofloxacin, macrolides, midazolam, nicardipine, nifedipine, norethisterone, omeprazole, pantoprazole, posaconazole, ranolazine; ritonavir, saquinavir, Chinese herbal remedies containing extracts of Schisandra sphenanthera, tamoxifen, theophylline, verapamil and voriconazole. Tacrolimus levels decreased by: carbamazepine, caspofungin, fosphenytoin, isoniazid, phenobarbital, phenytoin (fosphenytoin and phenytoin levels possibly increased), primidone, rifampicin, possibly rifabutin and St John’s wort. Increased nephrotoxicity with: aminoglycosides, amphotericin, NSAIDs, sulfamethoxazole, trimethoprim and vancomycin. Increased risk of hyperkalaemia with: potassiumsparing-diuretics and potassium salts. Anticoagulants: possibly increases concentration of dabigatran - avoid. Antipsychotics: avoid with droperidol, increased risk of ventricular arrhythmias. Antivirals: increased risk of nephrotoxicity with acyclovir, ganciclovir, valaciclovir and valganciclovir; concentration affected by efavirenz; concentration of both drugs increased with telaprevir; concomitant use with dasabuvir and ombitasvir/paritaprevir/ ritonavir is not recommended unless the benefits outweigh the risks, if used concomitantly, tacrolimus should not be administered on the day dasabuvir and ombitasvir/paritaprevir/ritonavir are initiated. Beginning the day after dasabuvir and ombitasvir/ paritaprevir/ritonavir are initiated; reinitiate tacrolimus at a reduced dose based on tacrolimus levels. The recommended tacrolimus dosing is 0.5 mg every 7 days, monitor levels at initiation and throughout treatment. Clotrimazole: more than doubles the bioavailability of tacrolimus (US-based researchers report that concomitant clotrimazole substantially increases the relative oral bioavailability of tacrolimus in renal transplant recipients. Inpharma. 2005 Dec 10; 1517: 15). Cytotoxics: concentration of afatinib possibly increased - separate dose by 6-12 hours; use crizotinib with caution; concentration increased by imatinib.

Technology Process of 1,14-Dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone

There total 36 articles about 1,14-Dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%