- CLEAVABLE TETRAZINE USED IN BIO-ORTHOGONAL DRUG ACTIVATION
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Disclosed is an advancement in provoked chemical cleavage. Thereby the invention provides the use of a diene as a chemically cleavable group attached to a Construct, and the use of a dienophile to provoke the release of the Construct by allowing the diene to react with a dienophile capable of undergoing an inverse electron demand Diels Alder reaction with the diene. The invention includes a kit for releasing a Construct CA bound to a Trigger TR, the kit comprising a tetrazine and a dienophile, wherein the Trigger is the tetrazine. The invention also includes the use of the formation of a pyridazine by reacting a tetrazine comprising a Construct CA bound thereto and a dienophile, as a chemical tool for the release, in a chemical, biological or physiological environment, of said Construct.
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Page/Page column 176-179
(2018/02/03)
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- METHOD FOR TREATING CHRONIC PAIN USING MEK INHIBITORS
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The invention features a method for treating chronic pain using a compound selected from formulae (I), (II)A, (I)B and (I)C.
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- Benzenesulfonamide derivatives and their use as MEK inhibitors
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Benzenesulfonamides of formula (I), in which W is OR1, NR2OR1, NRARB, NR2NRARB, or NR2(CH2)2-4NRARBand the other variables as defined in the claims, are inhibitors of MEK and are effective in the treatment of proliferative diseases, cancer, stroke, heart failure, xenograft rejection, arthritis, cystic fibrosis, hepatomegaly, cardiomegaly, Alzheimer's disease, complications of diabetes, septic shock, and viral infection.
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- Discovery of non-peptidic P2-P3 butanediamide renin inhibitors with high oral efficacy
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A new series of non-peptidic renin inhibitors having a 2-substituted butanediamide moiety at the P2 and P3 positions has been identified. The optimized inhibitors have IC50 values of 0.8 to 1.4nM and 2.5 to 7.6nM in plasma renin assays at pH 6.0 and 7.4, respectively. When evaluated in the normotensive cynomolgus monkey model, two of the most potent inhibitors were orally active at a dose as low as 3mg/kg. These potent renin inhibitors are characterized by oral bioavailabilities of 40 and 89% in the cynomolgus monkey. Inhibitor 3z (BILA 2157 BS) was selected as candidate for pre-development. Copyright (C) 1999 Elsevier Science Ltd.
- Simoneau, Bruno,Lavallee, Pierre,Anderson, Paul C.,Bailey, Murray,Bantle, Gary,Berthiaume, Sylvie,Chabot, Catherine,Fazal, Gulrez,Halmos, Ted,Ogilvie, William W.,Poupart, Marc-Andre,Thavonekham, Bounkham,Xin, Zhili,Thibeault, Diane,Boelger, Gordon,Panzenbeck, Maret,Winquist, Raymond,Jung, Grace L.
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p. 489 - 508
(2007/10/03)
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- Cu(II) CATALIZED HYDROLYSIS OF AN UNACTIVATED ESTER BASED ON REVERSIBLE CONJUGATE ADDITION.
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Cu(II) catalysis provides a 16,000-fold acceleration in the hydrolysis of methyl acrylate when a removable vicinal diamine ligand is used to increase the stability of the required copper chelate.
- Duerr, Brook F.,Czarnik, Anthony W.
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p. 6951 - 6954
(2007/10/02)
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- N-N-disubstituted alkenamides and phenylalkenamides
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Compounds of the formula STR1 where n is 0 or 1, R is alkyl, phenyl or R4 -substituted phenyl, R2 and R3 are, independently, alkyl or R2 and R3 together with N is STR2 m is 1, 2 or 3, R1 and R4 are, independently hydrogen, halo, alkyl or alkoxy, and R5 is hydrogen or alkyl of 1 to 6 carbon atoms or their pharmaceutically acceptable salts are useful as anti-diabetic agents, in particular, as hypoglycemic agents or inhibitors of post-prandial hypoglycemia.
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- 1-[(aminoalkyl and aminoalkylamino)carbonyl and thiocarbonyl]-α,α-diarylpyrrolidine, piperidine and homopiperidineacetamides and acetonitriles
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Novel 1-[(aminoalkyl and aminoalkylamino)carbonyl and thiocarbonyl]-α,α-diaryl-pyrrolidine, piperidine and homopiperidineacetamides and acetonitriles having the formula: STR1 wherein; n is zero, one or two; X is oxygen or sulfur; Z is STR2 p is 0 to 5 inclusive with the proviso that when Z is STR3 p is at least one; Y is aminocarbonyl or cyano; Ar1 and Ar2 are 2, 3 or 4-pyrido, phenyl or substituted phenyl; R is hydrogen or loweralkyl; R1, R2 and R3 are hydrogen, cycloalkyl, loweralkyl, phenyl, substituted phenyl, phenylloweralkyl, and R2 and R3 taken with the adjacent nitrogen may form a heterocyclic residue, and diastereoisomers when possible and pharmaceutical salts; and the method and pharmaceutical compositions for treating cardiac arrhythmias therewith are disclosed.
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