- Substrate Profiling of the Cobalt Nitrile Hydratase from Rhodococcus rhodochrous ATCC BAA 870
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The aromatic substrate profile of the cobalt nitrile hydratase from Rhodococcus rhodochrous ATCC BAA 870 was evaluated against a wide range of nitrile containing compounds (>60). To determine the substrate limits of this enzyme, compounds ranging in size from small (90 Da) to large (325 Da) were evaluated. Larger compounds included those with a biaryl axis, prepared by the Suzuki coupling reaction, Morita–Baylis–Hillman adducts, heteroatomlinked diarylpyridines prepared by Buchwald–Hartwig crosscoupling reactions and imidazo[1,2a]pyridines prepared by the Groebke–Blackburn–Bienaymé multicomponent reaction. The enzyme active site was moderately accommodating, accepting almost all of the small aromatic nitriles, the diarylpyridines and most of the biaryl compounds and Morita–Baylis–Hillman products but not the Groebke–Blackburn–Bienaymé products. Nitrile conversion was influenced by steric hindrance around the cyano group, the presence of electron donating groups (e.g., methoxy) on the aromatic ring, and the overall size of the compound.
- Mashweu, Adelaide R.,Chhiba‐Govindjee, Varsha P.,Bode, Moira L.,Brady, Dean
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- PYRIMIDINE AND TRIAZINE DERIVATIVES AND THEIR USE AS AXL INHIBITORS
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Compounds of the general formula(I): (I) processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
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Page/Page column 53-54
(2016/07/05)
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- Carboxamide Derivatives and Use Thereof
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The present disclosure provides substituted pyridyl-, pyrimidinyl-, pyrazinyl-, pyridazinyl-, and triazinyl-based carboxamides of Formula I-A: R10 Z-HET-E I-A and the pharmaceutically acceptable salts and solvates thereof, wherein Z, HET, Rsup
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Paragraph 0971; 0972
(2016/02/21)
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- As opioid receptor antagonists or inverse agonists of the novel compounds
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Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
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Paragraph 0346-0348; 0350; 0352
(2016/10/08)
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- BICYCLIC HETEROCYCLYL DERIVATES AS IRAK4 INHIBITORS
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The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors, wherein A, Y, Z, X1, X2, R1, R3, ‘m’, ‘n’ and ‘p’ have the meanings given in the specification and pharmaceutically acceptable salt or stereoisomer thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
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Paragraph 0135; 0136; 0214; 0215
(2016/12/16)
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- BICYCLIC HETEROCYCLYL DERIVATIVES AS IRAK4 INHIBITORS
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The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors. wherein A, Y, Z, X1, X2, X3, R1, R3, 'm', 'n' and 'p' have the meanings given in the specification and pharmaceutically acceptable salt or stereoisomer thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
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Page/Page column 23-24
(2015/07/23)
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- 2-Cyano-pyrimidines: A new chemotype for inhibitors of the cysteine protease cathepsin K
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Starting from the purine lead structure 1, a new series of cathepsin K inhibitors based on a pyrimidine scaffold have been explored. Investigations of P3 and P2 substituents based on molecular modeling suggestions resulted in potent cathepsin K inhibitors
- Altmann, Eva,Aichholz, Reiner,Betschart, Claudia,Buhl, Thomas,Green, Jonathan,Irie, Osamu,Teno, Naoki,Lattmann, René,Tintelnot-Blomley, Marina,Missbach, Martin
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p. 591 - 594
(2007/10/03)
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- BENZOFURAN DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS
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The invention relates to novel heterocycles of formula (I), processes for their preparation and their use for preparing medicaments for the treatment or prophylaxis of disorders, especially of hyperproliferative disorders.
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Page/Page column 91
(2008/06/13)
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- Phenoxyphenyl pyridines as novel state-dependent, high-potency sodium channel inhibitors
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In the search for more efficacious drugs to treat neuropathic pain states, a series of phenoxyphenyl pyridines was designed based on 4-(4-flurophenoxy) benzaldehyde semicarbazone. Through variation of the substituents on the pyridine ring, several potent state-dependent sodium channel inhibitors were identified. From these compounds, 23 dose dependently reversed tactile allodynia in the Chung model of neuropathic pain. Administered orally at 10 mg/kg the level of reversal was ca. 50%, comparable to the effect of carbamazepine administered orally at 100 mg/kg.
- Shao, Bin,Victory, Sam,Ilyin, Victor I.,Goehring, R. Richard,Sun, Qun,Hogenkamp, Derk,Hodges, Diane D.,Islam, Khondaker,Sha, Deyou,Zhang, Chongwu,Nguyen, Phong,Robledo, Silvia,Sakellaropoulos, George,Carter, Richard B.
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p. 4277 - 4285
(2007/10/03)
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- Aryl substituted pyridines, pyrimidines, pyrazines and triazines and the use thereof
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This invention relates aryl substituted pyridines, pyrimidines, pyrazines and triazines of Formula I: or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein A1, A2, A3, R1-R4, X and Y are set in the specification. The invention is also directed to the use of compounds of Formula I for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, as antitinnitus agents, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy.
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