- Design and synthesis of conformationally restricted inhibitors of active thrombin activatable fibrinolysis inhibitor (TAFIa)
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A series of 4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid and 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid derivatives designed as inhibitors of TAFIa has been prepared via a common hydrogenation-alkylation sequence starting from the appropriate benzimidazole and imidazopyridine system. We present a successful design strategy using a conformational restriction approach resulting in potent and selective inhibitors of TAFIa. The X-ray structure of compound 5 in complex with a H333Y/H335Q double mutant TAFI indicate that the conformational restriction is responsible for the observed potency increase.
- Brink, Mikael,Dahlen, Anders,Olsson, Thomas,Polla, Magnus,Svensson, Tor
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p. 2261 - 2268
(2014/04/17)
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- Acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase
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We report the discovery of novel uracil-based acyclic compounds as inhibitors of deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase), an enzyme involved in nucleotide metabolism that has been identified as a promising target for the development of
- Nguyen, Corinne,Ruda, Gian Filippo,Schipani, Alessandro,Kasinathan, Ganasan,Leal, Isabel,Musso-Buendia, Alexander,Kaiser, Marcel,Brun, Reto,Ruiz-Pérez, Luis M.,Sahlberg, Britt-Louise,Johansson, Nils Gunnar,González-Pacanowska, Dolores,Gilbert, Ian H.
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p. 4183 - 4195
(2007/10/03)
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- Anti-MRSA cephems. Part 2: C-7 cinnamic acid derivatives
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Forty-five novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described. The compounds contain novel cinnamic acid moieties at C-7 that were synthesized using a key Heck reaction followed by nucleophilic aromatic substitution reactions. The most active compound (41) displayed an MIC90 against MRSA of 1.0 μg/mL, and a PD50 of 0.8 mg/kg. Compound 14 was found to be very safe in a mouse model of acute toxicity.
- Springer, Dane M.,Luh, Bing-Yu,Goodrich, Jason,Bronson, Joanne J.
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p. 265 - 279
(2007/10/03)
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- Pharmaceuticals
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The present invention provides compounds of formula (I) as well as the use of such compounds in pharmaceutical compositions and methods of treatment. The compounds described herein represent a class of TAFIla inhibitors suitable for use in treating condit
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- Efficient synthesis of azetidine through N-trityl- or N- dimethoxytritylazetidines starting from 3-amino-1-propanol or 3- halopropylamine hydrohalides
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Efficient synthetic routes for the preparation of azetidine starting from commercially available 3-amino-1-propanol or 3-halopropylamine hydrohalides are reported. First, the appropriate N-trityl- or N-dimethoxytrityl protected tosyloxy- or halopropylamines were prepared. These precursors were then cyclized into the N-trityl- or N-dimethoxytritylazetidines. The N-protecting groups were removed in the presence of perchloric acid giving the hydrogen perchlorate salt of azetidine. The latter compound was transformed into its free base using a strong base under anhydrous conditions. The relatively expensive 4,4'-dimethoxytrityl chloride and less expensive trityl chloride used in these synthetic procedures were recycled in good yields. Azetidine hydrogenperchlorate can be used to prepare N-substituted azetidines without the need to isolate the free azetidine.
- Huszthy,Bradshaw,Krakowiak,Wang,Dalley
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p. 1197 - 1207
(2007/10/02)
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- 2-AMINOPYRIMIDINE-4-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION IN URINARY THERAPEUTICS
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A compound of formula (I) STR1 in which n denotes 2, 3, 4, or 5, p denotes 0 or 1,m denotes 0, 1, 2, 3, 4, or 5, and R 1 denotes a hydrogen atom or a methyl group,each X, which may be identical or different to any other X if m is greater than 1, denotes fluorine, chlorine, methoxy, isopropyl or cyclopropyl,in the form of a free base or an acid addition salt.
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- AMINOALKYL AND RELATED SUBSTITUTED PHOSPHINIC ACID ANGIOTENSIN CONVERTING ENZYME INHIBITORS
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Compounds of the structure STR1 are provided which are inhibitors of angiotensin converting enzyme and are useful in the treatment of hypertension.
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