| 1. |
- Nilsson, Jonas W., et al.
(author)
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Solid-phase synthesis of libraries generated from a 4-phenyl-2-carboxy-piperazine Scaffold
- 2001
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In: Journal of Combinatorial Chemistry. - : American Chemical Society (ACS). - 2156-8952 .- 1520-4766 .- 1520-4774. ; 3:6, s. 546-553
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Journal article (peer-reviewed)abstract
- Strategies for finding novel structures of therapeutical interest are discussed. The rationale for the selection of the two scaffolds N4-(m-aminophenyl)-piperazine-2-carboxylic acid E and N4-(o-aminophenyl)-piperazine-2-carboxylic F is described. The synthesis of the appropriate precursors to scaffold E and F and their use in solid-phase chemistry are described. A 160-member library was produced combining these novel piperazine scaffolds with eight sulfonyl chlorides/acid chlorides and 10 amines. The compound library prepared was analyzed using LC-MS, showing the expected base peak in all wells at an average purity of 82%.
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| 2. |
- Nilsson, Jonas W., et al.
(author)
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Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold : Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex
- 2001
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 46:19, s. 3985-4001
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Journal article (peer-reviewed)abstract
- A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to mimic d-Phe-Pro in the thrombin inhibiting tripeptide d-Phe-Pro-Arg. The arginine in d-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of α-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 μM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with α-thrombin is discussed.
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| 3. |
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| 4. |
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| 5. |
- Dahlgren, Anders, et al.
(author)
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Novel morpholinone-based D-Phe-Pro-Arg mimics as potential thrombin inhibitors : design, synthesis, and X-ray crystal structure of an enzyme inhibitor complex
- 2002
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In: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 10:6, s. 1829-1839
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Journal article (peer-reviewed)abstract
- A morpholinone structural motif derived from d(+)- and l(−)-malic acid has been used as a mimic of d-Phe-Pro in the thrombin inhibiting tripeptide d-Phe-Pro-Arg. In place of Arg the more rigid P1 truncated p-amidinobenzylamine (Pab) or 2-amino-5-aminomethyl-3-methyl-pyridine have been utilized. The synthetic strategy developed readily delivers these novel thrombin inhibitors used to probe the α-thrombin inhibitor binding site. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 720 nM. The X-ray crystal structure of this candidate co-crystallized with α-thrombin is discussed.
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| 6. |
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| 7. |
- Nilsson, GA, et al.
(author)
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New halogen-specific detector applied to the analysis of chlorinated fatty acids
- 2001
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In: Journal of Chromatography A. - 0021-9673. ; 912:1, s. 99-106
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Journal article (peer-reviewed)abstract
- A new halogen-specific detection method (XSD) was tested for determination of chlorinated fatty acids in marine biota. In XSD, an increased emission of ions and electrons is caused by the high-temperature combustion of halogen-containing compounds. The detection limit of methyl dichlorooctadecanoate and the selectivity at a reactor temperature of 900 degreesC match those of electrolytic conductivity detection (ELCD). The relative standard deviation is less than 11% for greater than or equal to0.2 ng methyl dichlorooctadecanoate. An XSD chromatogram of a complex sample, chlorinated fatty acid methyl esters liberated from fish lipids, agreed with a previously obtained ELCD chromatogram. (C) 2001 Elsevier Science B.V. All rights reserved.
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| 8. |
- Nilsson, Ingemar, et al.
(author)
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Missfärgande mikroorganismer på råspont
- 2006
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Reports (peer-reviewed)abstract
- Oförklarlig missfärgande påväxt på råspont har uppstått i många vindar, på takutsprång och på fristående tak i carportar. En förklaring till denna påväxt skulle kunna vara att torkningen av virke orsakat en anrikning av näringsämnen på ytan och att dessa ämnen gynnat tillväxt av missfärgan¬de svampar. Projektet har genomförts med provvirke från olika sågverk som har torkats vid olika tempe¬raturer. Proven har analyserats dels med avseende på förekomst av näringsämnen dels med avseende på möglingsbenägenhet på ytor som torkat fritt och på ytor där uttork¬ningen har begränsats av strö. Resultaten tyder på att summahalten av lågmolekylära sockerarter är högre på ytor som torkat fritt än på ytor vid strö. Den mykologiska analysen visar större grad av påväxt på de ytor som torkat fritt. För att kunna ge svar på åtgärder för redan inträffade skador och framför allt på föränd¬ringar för att undvika framtida problem behöver kompletterande analyser av summahalten av lågmolekylära sockerarter göras i en profil i träytan.
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| 10. |
- Olsson-Strömberg, Ulla, et al.
(author)
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Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase
- 2006
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In: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 47:9, s. 1768-73
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Journal article (peer-reviewed)abstract
- The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.
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