- Removable phosphine reagents for the Mitsunobu reaction
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We have developed a novel triphenylphosphine replacement for the Mitsunobu reaction. We have demonstrated that 4-diphenylphosphanyl-benzoic acid 2-trimethylsilanyl-ethyl ester (DPPBE) is an efficient reagent and greatly facilitates the isolation of the desired product.
- Yoakim, Christiane,Guse,O'Meara,Thavonekham
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- Discovery of (1R,6S)-5-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]-3,4- diaza-bicyclo[4.1.0]hept-4-en-2-one (R,S-4a): Histamine H3 receptor inverse agonist demonstrating potent cognitive enhancing and wake promoting activity
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A series of fused cyclopropyl-4,5-dihydropyridazin-3-one (3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one) phenoxypiperidine analogs was designed and synthesized, leading to the identification of (1R,6S)-5-[4-(1-cyclobutyl- piperidin-4-yloxy)-phenyl]-3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one (R,S-4a) as a second-generation pyridazin-3-one H3R antagonist. Compound R,S-4a was a potent H3R functional antagonist in vivo in the rat dipsogenia model, demonstrated potent wake activity in the rat EEG/EMG model, and enhanced short-term memory in the rat social recognition memory model at doses as low as 0.03-0.3 mg/kg po.
- Hudkins, Robert L.,Josef, Kurt A.,Becknell, Nadine C.,Aimone, Lisa D.,Lyons, Jacquelyn A.,Mathiasen, Joanne R.,Gruner, John A.,Raddatz, Rita
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.
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Page/Page column 113
(2020/08/13)
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- CONJUGATED PROTEINS AND USES THEREOF
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Disclosed herein, in certain embodiments, are protein-probe adducts and synthetic ligands that inhibit protein-probe adduct formation, in which the proteins are regulated by NRF2. In some instances, also described herein are protein-binding domains that interact with a probe and/or a ligand described herein, in which the proteins are regulated by NRF2.
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Paragraph 0387; 0391-0392
(2020/09/16)
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- Synthesis of 11C-labelled ureas by palladium(II)-mediated oxidative carbonylation
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Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [11C]carbon monoxide. Starting with amines and [11C]carbon monoxide, both symmetrical and unsymmetrical 11C-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [11C]carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/μmol-319 GBq/μ mol). DFT calculations were found to support a reaction mechanism proceeding through an 11C-labelled isocyanate intermediate.
- Roslin, Sara,Brandt, Peter,Nordeman, Patrik,Larhed, Mats,Odell, Luke R.,Erikssoni, Jonas
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- SUBSTITUTED THIAZOLE OR OXAZOLE P2X7 RECEPTOR ANTAGONISTS
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The present invention refers to novel substituted thiazole and oxazole compounds of formula (I) having P2X7 receptor (P2X7) antagonistic properties. The compounds are useful in the treatment or prophylaxis of diseases associated with P2X7 receptor activity in animals, in particular humans.
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Page/Page column 34
(2015/09/22)
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- Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors
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A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has been identified via molecular scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects.
- Xin, Zhili,Zhao, Hongyu,Serby, Michael D.,Liu, Bo,Liu, Mei,Szczepankiewicz, Bruce G.,Nelson, Lissa T.J.,Smith, Harriet T.,Suhar, Tom S.,Janis, Rich S.,Cao, Ning,Camp, Heidi S.,Collins, Christine A.,Sham, Hing L.,Surowy, Teresa K.,Liu, Gang
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scheme or table
p. 4298 - 4302
(2009/04/06)
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- Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors
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Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin
- Liu, Gang,Lynch, John K.,Freeman, Jennifer,Liu, Bo,Xin, Zhili,Zhao, Hongyu,Serby, Michael D.,Kym, Philip R.,Suhar, Tom S.,Smith, Harriet T.,Cao, Ning,Yang, Ruojing,Janis, Rich S.,Krauser, Joel A.,Cepa, Steven P.,Beno, David W. A.,Sham, Hing L.,Collins, Christine A.,Surowy, Teresa K.,Camp, Heidi S.
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p. 3086 - 3100
(2008/02/10)
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- Peptide compounds
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The present invention relates to a compound of the formula (I)wherein R1 is benzofuranyl substituted by halogen, or styryl substituted by halogen; R2 is substituted hydroxy, substituted mercapto or substituted sulfonyl; and X is or pharmaceutically acceptable salts thereof. The compound (1) of the present invention and pharmaceutically acceptable salts thereof possess a strong inhibitory activity on the production of nitric oxide (NO), and are useful for prevention and/or treatment of NO-mediated diseases in human being and animals.
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- Utility of azetidinium methanesulfonates for radiosynthesis of 3-[ 18F]fluoropropyl amines
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3-Methanesulfonyloxypropyl tertiary amines were observed to cyclize to form azetidinium methanesulfonate moieties. Heat-induced cyclization of 3-methanesulfonyloxypropyl amines was utilized for preparation of azetidinium methanesulfonates. The azetidinium methanesulfonates were found to incorporate radioactive [18F]fluoride (decay-corrected yields > 60%) efficiently, resulting in an efficient synthesis of 3-[18F] fluoropropyl tertiary amines. Copyright
- Kiesewetter, Dale O.,Eckelman, William C.
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p. 953 - 969
(2007/10/03)
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- Dipeptides which promote release of growth hormone
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Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis. STR1
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