Immunosuppressants following organ

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine dmgs, such as 6-mercaptopurine (6-MP), 6-thioguanine and azathioprine, to inactive metabolites [29-32]. Thiopurines form part of the routine treatment for patients with acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune diseases such as SLE and Crohn s disease, and are used as an immunosuppressant following organ transplantation. 

Utility Immunosuppressants Following Organ Transplant Procedures... 

Diaryl sulfide, (I) and (II), prepared by the authors (2) and Marsilje (3), respectively, were effective in mediating by lymphocyte interactions with EDG receptors and used as immunosuppressants following organ transplant procedures. 

D.M. Armistead et al, US Patent 6,967,214 (November 22, 2005) Assignee Vertex Pharmaceuticals Incorporated Utility Immunosuppressants Following Organ Transplant Procedures... 

Immunocompromised patients are at increased risk for the development of cutaneous melanoma. Immunodehciency includes those individuals with ataxia telangiectasia, chronic lymphocytic leukemia, Hodgkin s lymphoma, and immunosuppression following organ transplant. Acquired immunodehciency syndrome also has been shown to increase the risk of developing cutaneous melanoma. Personal history of nonmelanoma or melanoma skin cancers is a risk factor for subsequent melanoma. 

Muromonab-CD3 (Orthoclone OKT3) [Immunosuppressant/ Monoclonal Antibody] WARNING Can cause anaphylaxis monitor fluid status Uses Acute rejection following organ transplantation Action Murine Ab, blocks T-cell Fxn Dose Per protocol Adults. 5 mg/d IV for 10-14 d Peds. 0.1 mg/kg/d IV for 10-14 d Caution [C, /-] w/ Hx Szs, PRG, uncontrolled HTN Contra Murine sensitivity, fluid overload Disp Inj SE Anaphylaxis, pulm edema, fever/chills w/ 1st dose (premedicate w/ stCToid/APAP/antihistamine) Interactions t Effects W/ immunosuppressives t effects OF live virus vaccines t risk of CNS effects encephalopathy W/ indomethacin EMS Monitor for S/Sxs of Infxn monitor resp Fxn, known to... 

Azathioprine (Imuran) is an immunosuppressant drug that is often used to prevent tissue rejection following organ transplants. Because of its immunosuppressant properties, this drug has been employed in treating... 

Clinical Use. Cyclosporine (Neoral, Sandimmune) is one of the primary medications used to suppress immune function following organ transplantation.14 21 69 This medication can be used alone or combined with glucocorticoids, azathioprine, and other immunosuppressants to prevent the rejection of a kidney, lung, liver, heart, pancreas, and other organ transplants. 

Some phenylalanine-derived monocyclic azetidin-2-ones, for example, 564, have been reported as modest inhibitors of human cytomegalovirus (HCMV) serine protease <2004BML2253>. HCMV is a ubiquitous member of the herpes virus family. Severe manisfestations of HCMV can be seen in individuals with a weakened immune system due to late-stage cancer and AIDS, or by immunosuppressive therapy following organ transplantation. 

POST-TRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS Following organ transplantation and associated immunosuppression, a range of post-transplantation lymphoproliferative disorders can develop. Histologic,... 

The efficacy of tacrolimus as a primary immunosuppressant for the prophylaxis of rejection and for rescue therapy following failure of conventional cyclosporin-based rejection prophylaxis has been demonstrated in numerous clinical studies in adults and pediatrics using various types of combination therapy since 1989. Tacrolimus is now well established not only as a primary immunosuppressant in organ transplantation but also an excellent rescue agent for patients experiencing posttransplant rejection while on cyclosporin-based regimens [44]. 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

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