Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitrooxyalkyl ethers and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors

A series of 3-substituted 1,5-diarylpyrroles bearing a nitrooxyalkyl side chain linked to different spacers were designed. New classes of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as COX-2 selective inhibitors and NO donors were synthesized and are herein reported. By taking into account the metabolic conversion of nitrooxyalkyl ethers (9, 10) into corresponding alcohols, derivatives 17 and 18 were also studied. Nitrooxy derivatives showed NO-dependent vasorelaxing properties, while most of the compounds proved to be very potent and selective COX-2 inhibitors in in vitro experimental models. Further in vivo studies on compounds 9a,c and 17a highlighted good anti-inflammatory and antinociceptive activities. Compound 9c was able to inhibit glycosaminoglycan (GAG) release induced by interleukin-1β (IL-1β), showing cartilage protective properties. Finally, molecular modeling and (1)H- and (13)C-NMR studies performed on compounds 6c,d, 9c, and 10b allowed the right conformation of nitrooxyalkyl ester and ether side chain of these molecules within the COX-2 active site to be assessed

Modification of rhenium carbonyls with thienyl nucleophiles

In the reaction between [Re(CO)5Br] and 2–lithiumthienyl, X–ligand substitution was expected. Li+{C4H3S}¯did not substitute Br¯, but an intermediate negatively charged complex was obtained (non–mobile on silica gel) and it was found that the thienyl had bonded to a carbonyl ligand, producing a dirhenium acylate complex. Such complexes are the precursors to neutral Fischer carbene complexes. After alkylation with Et3OBF4, [Re2 (CO) 9C(OEt)C4H3S] (1) was obtained, instead of a monorhenium monocarbene complex. Greater yields of 1 could be obtained, from reactions with [Re2(CO) 10] instead of [Re(CO) 5Br]. [Re2 (CO) 10] reacted with 5–lithium–2,2'–bithienyl and 2–lithium–3,6– dimethylthieno[3,2–b]thienyl and was then alkylated with Et3OBF4. The reactions proceeded smoothly and [Re2 (CO) 9C(OEt)C8H5S2] (2) and [Re2 (CO) 9C(OEt)C8H7S2] (3) were obtained. The substrates thiophene, 2,2'–bithiophene and 3,6–dimethylthieno[3,2–b]thiophene, can all be doubly lithiated under appropriate reaction conditions. These lithiated species were reacted with two equivalents of [Re2 (CO) 10]. In the case of bithiophene this produced, in good yield, the tetrametal biscarbene complex [Re2 (CO) 9C(OEt)C8H4S2C(OEt)Re2 (CO) 9] (8). In the thiophene and dimethylthieno[3,2–b]thiophene cases [Re2 (CO) 9C(OEt)C4H2SC(OEt)Re2 (CO) 9] (7) and [Re2 (CO) 9C(OEt)C8H6S2C(OEt)Re2 (CO) 9] (9) could be isolated in meagre quantities. This was ascribed to poor double lithiation (also steric hindrance in the case of 7). The carbene ligands reacted with water on the silica gel during column chromatography or in a control experiment with degassed water to produce aldehydes by reductive elimination from the metal. Protonation of the acylrhenate afforded rhenium hydrides which is also a potential precursor to aldehyde formation. This is believed to be a facile process for especially complex 9, isolated in very small quantity. Complexes 7–9 produced monocarbene aldehyde complexes [Re2(CO) 9C(OEt)C4H2SC(O)H] (12), [Re2 (CO) 9C(OEt)C8H4S2C(O)H] (13) and [Re2 (CO) 9C(OEt)C8H6S2C(O)H] (14), as well as dialdehyde compounds. Complexes 2 and 3 also produced aldehyde compounds. The formation of aldehydes from ethoxycarbene complexes is believed to involve hydroxycarbene intermediate species. Experiments were performed on [Re2 (CO) 10] and [Re(CO) 5Br]. They were reacted with 2–lithiumthienyl and then protonated. In the case of [Re2(CO) 10], hydride signals were observed on the 1H NMR spectrum, as well as aldehyde signals. In the case of [Re(CO) 5Br] there was strong NMR evidence indicating the formation of a hydroxycarbene complex. Complexes 1, 2, and 3 were reacted with Br2 (l). The metal–metal bonds were cleaved by the bromine to produce monorhenium carbene complexes [Re(CO) 4{C(OEt)C4H3S}Br] (4), [Re(CO) 4{C(OEt)C8H5S2}Br] (5), and [Re(CO) 4{C(OEt)C8H7S2}Br] 6) and [Re(CO) 5Br]. Complex 8 reacted with bromine to produce a monocleaved complex [Re2 (CO) 9C(OEt)C8H4S2C(OEt)Re(CO) 4Br] (11) and a biscleaved complex [Re(CO) 4Br{C(OEt)C8H4S2C(OEt)}Re2 (CO) 4Br] (10). Unique complexes [Re(CO) 4{C(OH)C4H3S}{μ–H}Re(CO) 4{C(O)C4H3S}] (15) and [Re(CO) 4{C(OH)C8H5S2}{μ–H}Re(CO) 4{C(O) C8H5S2}] (16) were obtained by starting with [Re(CO) 5Br] or [Re2 (CO) 10] and reacting them with 2–lithiumthienyl and 5–lithium–2,2'– bithienyl. These complexes were isolated from the column as very polar compounds after eluation of the aldehyde complexes. The dirhenium complex was obtained with a carbonyl– modified ligand (hydroxycarbene/acyl) on each of the metals. The complexes consist of two fragments held together by a hydrogen atom that bridges the two rhenium atoms (hydrido) and one that bridges the oxygen atoms of the carbene/acyl ligands (protonic).Thesis (PhD)--University of Pretoria, 2011.Chemistryunrestricte

Oxford, Bodleian Library, MS. Lat. Th. d.24 (30591): Aldhelm, "De laudibus virginitatis" ("Yale Aldhelm Fragments': 2 leaves) (with 92, 172, 1736, 330, 334a, 372,438)

395. Oxford, Bodleian Library, MS. Lat. th. d.24 (30591) Aldhelm, "De laudibus virginitatis" ("Yale Aldhelm Fragments': 2 leaves) (with 92, 172, 1736, 330, 334a, 372,438) [Ker 12; Gneuss 857] HISTORY: Two detached leaves, part of the dispersed 9c "Yale" Aldhelm (see 330). Folio 1 was first referenced in the Bodleian in 1893: it was "Part of a series of unreferenced fragments etc. arranged as Palaeographical Specimens which was broken up in 1895" (S.C. 30479; originally catalogued as MS. Lat. th. f. 2 (P)). Folio 2 was given to the Bodleian by H. W. Garrod in 1942, at which time the two leaves were bound together (Bodleian Library Record 1942: 66). &nbsp

Quonset Hut 7

Entry created by John H. Herrick October 17, 1973John H. Herrick Archives: Documenting Structures at The Ohio State UniversityThe University Archives has determined that this item is of continuing value to OSU's history.Quonset Hut 7 was located at 2332 Kenny Road. Never officially named by Board of Trustees action. Built under the name of "Veterans Educational Facilities, Building 9C, Farm Management Laboratory," alternate names include "Wood Working Shop". The building was razed in August 1984

Study of Dehydration of Ricinoleic of Castor Oil By P2O5

The aim of this research is to find out the best temperature, time and amount of dehydrator on dehyration of ricinoleic of castor oil by P2O5. Dehydration as means to obtain linoleic and CLA (conjugated linoleic acid) as glyseride forms. Dehydration was carried out using various temperature, time and amount of dehydrator. The reaction medium was maintained under vacuum through by silica gel to reduced water, gentle bubling with nitrogen thorough by Mg to prevent oxidation, and used Zn powder as an antipolymerization agent. Dehydration was followed by GC which the best result was caused the lowest ricinoleic and the highets linoleic and CLA. Identification was done by FTIR, UV and GC- MS and it was compared with the standard. The best dehydration was obtain for 200oC, 3% (w/w) P2O5, and 4 h with a convertion factor (yield) of 97,94%. The composition of best result was: 1.02% (9c – 12c) linoleic, 41.97% (9c/t – 12t/c) linoleic, 19.50% (9c/t-12t/c) CLA, 4.89% (9t – 12t)linoleic,19.79%(9t–11t)CLA and0.94%ricinoleic.TheratioofCLA:linoleicofdehydrated was 0.82 : 1 or 76.18 % compared to the standard CLA with the proportions of 1.45:1

Functional Studies of CCAAT/Enhancer Binding Protein Site Located Downstream of the Transcriptional Start Site.

Previous studies have identified a CCAAT/enhancer binding protein (C/EBP) site located downstream of the transcriptional start site (DS3). The role of the DS3 element with respect to HIV-1 transactivation by Tat and viral replication has not been characterized. We have demonstrated that DS3 was a functional C/EBPβ binding site and mutation of this site to the C/EBP knockout DS3-9C variant showed lower HIV-1 long terminal repeat (LTR) transactivation by C/EBPβ. However, it was able to exhibit similar or even higher transcription levels by Tat compared to the parental LTR. C/EBPβ and Tat together further enhanced the transcription level of the parental LAI-LTR and DS3-9C LTR, with higher levels in the DS3-9C LTR. HIV molecular clone viruses carrying the DS3-9C variant LTR demonstrated a decreased replication capacity and delayed rate of replication. These results suggest that DS3 plays a role in virus transcriptional initiation and provides new insight into C/EBP regulation of HIV-1

Computing Permutation Encodings

We consider some encodings of permutations of the first N natural numbers, discuss some relations among them and how one can be computed from others. We show a short proof of an existing efficient algorithm for one encoding, and present two new efficient algorithms for encoding permutations. One of these algorithms is constructed as the inverse of an existing algorithm for decoding, making it the first efficient permutation encoding algorithm obtained that way

Brou\'e's abelian defect group conjecture holds for the Harada-Norton sporadic simple group HNHN

In representation theory of finite groups, there is a well-known and important conjecture due to M. Brou\'e. He conjectures that, for any prime $p$, if a $p$-block $A$ of a finite group $G$ has an abelian defect group $P$, then $A$ and its Brauer corresponding block $B$ of the normaliser $N_G(P)$ of $P$ in $G$ are derived equivalent (Rickard equivalent). This conjecture is called Brou\'e's abelian defect group conjecture. We prove in this paper that Brou\'e's abelian defect group conjecture is true for a non-principal 3-block $A$ with an elementary abelian defect group $P$ of order 9 of the Harada-Norton simple group $HN$. It then turns out that Brou\'e's abelian defect group conjecture holds for all primes $p$ and for all $p$-blocks of the Harada-Norton simple group $HN$.Comment: 36 page