Academic literature on the topic 'Sels de thiazolium'

Two hydrate pseudopolymorphs of 3-[(4-amino-2-methylpyrimidin-1-ium-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl hydrogen pyrophosphate (TPP),viz.a dihydrate, C12H18N4O7P2S·2H2O, (I), and a trihydrate, C12H18N4O7P2S·3H2O, (II), were obtained during a structural study of vitamin B1 coenzyme. In both compounds, TPP is a neutral zwitterion, with its pyrophosphate group doubly deprotonated and its pyrimidine ring protonated, and it assumes the usual `F' conformation in terms of the two torsion angles about the bonds by which the methylene group links the thiazolium and pyrimidinium rings [1.1 (3) and 79.7 (3)° for (I), and 2.0 (3) and 75.5 (3)° for (II)]. In (I), two TPP molecules are linked by a pair of O—H...O hydrogen bonds into a phosphate-pairing dimer. N—H...O hydrogen bonds connect the dimers into a sheet parallel to (101). In (II), the TPP molecules are self-assembled solely by N—H...O hydrogen bonds, generating a tape structure along [001]. A comparison of the four known hydrate pseudopolymorphs of TPP shows that the phosphate-pairing dimers are basic building units for the formation of two-dimensional networks.

Norovirus infection is a major cause of nonbacterial gastroenteritis and is a self-limited infection in immunocompetent patients. However, in immune compromised patients, norovirus has been reported to cause prolonged infection resulting in complications such as graft versus host disease and sepsis due to mucosal breakdown. Supportive care is the only current therapy for norovirus as attempts to treat norovirus with ribavirin or oral immunoglobulin have been unsuccessful. Nitazoxanide is a thiazolide antimicrobial with broad activity against anaerobic bacteria, protozoa, and a range of viruses in cell culture models. The antiviral activity of nitazoxanide may relate to activation of natural host antiviral defenses, but there is also evidence for a direct-acting antiviral effect on cellular processes possibly through inhibition of virus protein production/maturation and/or assembly. We report our experience treating norovirus gastroenteritis occurring in 12 patients after (9) or prior to (3) HSCT with Nitazoxanide. From November 2012 to July 2013, 12 patients (2 receiving chemotherapy, 1 autologous HSCT and 9 allogeneic HSCT) developed norovirus gastroenteritis. Ages ranged from 1 to 21 years (median 10) diagnoses included ALL/AML (6), aplastic anemia (2), and 1 each for osteopetrosis, Wiskott Aldrich, neuroblastoma, and brain tumor. Norovirus was detected by RNA RT-PCR test of stool performed by Focus Diagnostics, Cypress, Ca. The dose of Nitazoxanide was 100 mg po BID for ages 1 to 4 years, 200 mg po BID for age 4 to 11 years, and 500 mg po BID for greater than 11 years. One patient, 33 months post HSCT with normal immune studies was not treated as his symptoms resolved prior to availability of test results. All other patients clinically responded with improvements in diarrhea, nausea, and abdominal pain within 2-4 days (median 2 days). Three patients were pre-HSCT on chemo/immunotherapy and 8 patients were 1 day to 34 months after HSCT. All of the treated patients were on immune suppression or chemotherapy. Eight allogeneic HSCT patients were on immunosuppression and four of these patients had GVHD at onset of symptoms. Immune suppression included tacrolimus/solumedrol (3), cellcept/solumedrol (2) plus infliximab (1), tacrolimus (1), cyclosporine (1). Three patients were receiving immunotherapy (1), or chemotherapy for solid tumors (2) prior to planned HSCT. Clearance of stool virus was variable. Two of 3 patients treated prior to HSCT became negative on stool study within 3-14 days of treatment (1 unknown duration). Among patients treated after HSCT 5 of 8 had persistent viral shedding, 2 received drug until death (1 adenovirus, 1 congestive heart failure) both were treated greater than 2 months, 3 with GVHD continue to shed virus after 6 months of treatment, and 3 have come off therapy and remain negative for norovirus RNA. One HSCT patient with clinical resolution but persistent viral shedding stopped treatment resulting in re-occurrence of clinical symptoms. This patient responded clinically to reinstitution of therapy within 2 days but continues to shed virus. UGI endoscopy and colonoscopy were performed in 5 patients at the time of clinical infection, all showed inflammation and edema but no GVHD was seen on histology. Peripheral blood CD4 counts among those with persistent viral shedding ranged from<50-445/ul and for those that cleared virus 143-1222/ul. Nitazoxinide is effective therapy for norovirus gastroenteritis in immune compromised patients. Therapy needs to be continued until stool RNA studies become negative. Disclosures: Off Label Use: Nitazoxide is a thiazolide antimicrobial that is FDA approved for treatment of cryptosporidium and is known to have broad spectrum activity to bacteria and viral infections. We used it to treat norovirus infections in immune compromised SCT patients.

L'objectif de ce travail est l'etude de la reactivite des isonitriles avec les sels d'iminium afin d'acceder a de nouveaux heterocycles. L'addition des chlorothioimidates de methyle sur les aldimines, en presence d'un isonitrile, conduit aisement aux chlorures d'amino-4 methylthio-2 imidazolium. Par un procede identique, des chlorures de diamino-4,5 methylthio-2 thiazolium ont ete obtenus en remplacant les aldimines par le dimethylthioformamide. Nous avons montre que ces cyclocondensations a trois composants font intervenir des sels de n--(methylthio) formimidoyl iminium ou de n-(dithiomethoxycarbonyl) formamidinium qui sont rapidement pieges par l'isonitrile selon une cycloaddition 4#++1. La reactivite des sels d'imidazolium et de thiazolium a ete examinee: hydrolyse, decomposition par perte d'isobutene ou de chlorure de methyle, comportement en presence d'une base et d'un dipolarophile. Les iodures de n--(methylthio) benzylidene ou ethylidene amidinium et de (methylthio)-3 propene-2 iminium-1 sont connus dans la litterature. Nous les avons opposes aux isonitriles. Nous pouvons degager les resultats suivants: 1) les iodures de formamidinium additionnent aisement un ou deux equivalents d'isonitrile pour donner des imidazoles ou des azetidines; 2) quelques sels de 2h-pyrrolium ont ete isoles au depart des iodures d'acetamidinium. Les mecanismes reactionnels ont ete etablis. D'une facon generale, les imidazoles, les thiazoles et les thiophenes prepares au cours de ce travail s'oxydent par simple contact avec l'oxygene atmospherique. Ils donnent des heterocycles hydroxyles ou des polyenes conjugues comportant une ou deux fonctions carbonylees

La première partie de notre thèse concerne les traitements actuels du paludisme et les différentes approches de développement de nouveaux médicaments. Dans une seconde partie , nous présenterons la série chimique sur laquelle nous avons travaillé. Il s'agit de molécules inhibant le métabolisme phospholipidique de Plasmodium. La troisième partie concerne la mise au point et la validation d'une méthode de dosage de deux composés bi-cationiques et de deux prodrogues dans le plasma et les érythrocytes. Cette méthode a été validée conformément aux recommandations de la FDA. Dans une quatrième partie, nous présenterons les études d'activité in-vitro et in-vivo ainsi que les études de conversion prodrogue-drogue in vitro. La détermination du pourcentage de liaison aux protéines plasmatiques des deux composés bi-cationiques fera l'objet de la cinquième partie. Les deux dernières parties concernent les études pharmacocinétiques des composés T3 et T4 de la prodrogue TE3 réalisées chez le rat.