- Discovery of novel heterocyclic factor VIIa inhibitors
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Structure-activity relationships and binding mode of novel heterocyclic factor VIIa inhibitors will be described. In these inhibitors, a highly basic 5-amidinoindole moiety has been successfully replaced with a less basic 5-aminopyrrolo[3,2-b]pyridine sca
- Rai, Roopa,Kolesnikov, Aleksandr,Sprengeler, Paul A.,Torkelson, Steven,Ton, Tony,Katz, Bradley A.,Yu, Christine,Hendrix, John,Shrader, William D.,Stephens, Robin,Cabuslay, Ronnell,Sanford, Ellen,Young, Wendy B.
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- HETEROARYLAMINOISOQUINOLINES, METHODS FOR THEIR PREPARATION AND THERAPEUTIC USES THEREOF
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The application is directed to compounds of formula (IA) : and specifically compounds of formula (I) and their salts and solvates, wherein R1, R11, R12, R13, R4, R5, n, A1, A2, and A3 are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of conditions associated with the alteration of the activity of β-galactosidase, specially galactosidase beta-1 or GLB1, including GM1 gangliosidoses and Morquio syndrome, type B.
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Page/Page column 103; 104
(2016/08/23)
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- Azonia Aromatic Cations by Ring-Closing Metathesis: Synthesis of Azaquinolizinium Cations
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A strategy based on a ring-closing metathesis (RCM) reaction of pyridinium azadienes in the presence of the second generation Grubbs catalyst was employed as a new approach to synthesize the 1-azaquinolizinium (pyrido[1,2-a]pyrimidin-5-ium) heterocycle and some simple derivatives. This method was also successfully applied to the first reported synthesis of the benzo-1-azaquinolizinium (pyrimido[2,1-a]isoquinolinium) cation by using the Hoveyda-Grubbs catalyst in Cl2CHCHCl2 at 130 C.
- Abeng?zar, Alberto,Abarca, Beatriz,Cuadro, Ana M.,Sucunza, David,álvarez-Builla, Julio,Vaquero, Juan J.
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p. 4214 - 4223
(2015/06/30)
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- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
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Paragraph 001167; 001168
(2015/09/28)
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- TRICYCLIC ALKYNES THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN
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The present invention relates to tricyclic alkyne compounds of formula I that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where gluco
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Page/Page column 68
(2014/03/25)
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- Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 3. Structure-activity relationships within the aryl carbinol region of the N-arylsulfonamido-N′-arylpiperazine series
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We have recently reported a novel approach to increase cytosolic glucokinase (GK) levels through the binding of a small molecule to its endogenous inhibitor, glucokinase regulatory protein (GKRP) these initial investigations culminated in the identification of 2-(4-((2S)-4-((6-amino-3- pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3, 3-hexafluoro-2-propanol (1, AMG-3969), a compound that effectively enhanced GK translocation and reduced blood glucose levels in diabetic animals. Herein we report the results of our expanded SAR investigations that focused on modifications to the aryl carbinol group of this series. Guided by the X-ray cocrystal structure of compound 1 bound to hGKRP, we identified several potent GK-GKRP disruptors bearing a diverse set of functionalities in the aryl carbinol region. Among them, sulfoximine and pyridinyl derivatives 24 and 29 possessed excellent potency as well as favorable PK properties. When dosed orally in db/db mice, both compounds significantly lowered fed blood glucose levels (up to 58%).
- Nishimura, Nobuko,Norman, Mark H.,Liu, Longbin,Yang, Kevin C.,Ashton, Kate S.,Bartberger, Michael D.,Chmait, Samer,Chen, Jie,Cupples, Rod,Fotsch, Christopher,Helmering, Joan,Jordan, Steven R.,Kunz, Roxanne K.,Pennington, Lewis D.,Poon, Steve F.,Siegmund, Aaron,Sivits, Glenn,Lloyd, David J.,Hale, Clarence,St. Jean, David J.
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supporting information
p. 3094 - 3116
(2014/05/06)
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- SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN
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The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
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Page/Page column 59; 60
(2013/08/28)
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- Imidazopyridine derivatives as PI3K inhibitors
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New imidazopyridine derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks)
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Page/Page column 41
(2012/11/13)
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- IMIDAZOPYRIDINE DERIVATIVES AS PI3K INHIBITORS
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New imidazopyridine derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks).
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Page/Page column 95
(2012/11/13)
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- PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY
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Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazoles of Formula I, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.
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Page/Page column 54
(2011/02/15)
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- SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
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Substituted cyclopropyl compounds of the formula I: are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.
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Page/Page column 111-112
(2011/02/24)
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- PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLE SULFONAMIDES AND THEIR USE IN CANCER THERAPY
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Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazole sulfonamides, e.g., compounds of Formulae IA, IB, and IC, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.
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Page/Page column 96-97
(2010/10/19)
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- QUINAZOLINONE AND FUSED PYRIMIDINONE COMPOUNDS AND THEIR USE IN TREATING SODIUM CHANNEL-MEDIATED DISEASES OR CONDITIONS
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This invention is directed to compounds of formula (I): wherein (A), n, R1, R2 and R3 are as defined herein, as a stereoisomer, enantiomer, tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.
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Page/Page column 101
(2008/12/07)
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- A Simple Method for the Protection of Aryl Amines as their t-Butylcarbamoyl (Boc) Derivatives
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It has been found that aryl amines can be directly protected as their Boc derivatives by treatment of the amine with two equivalents of NaHMDS in THF followed by one equivalent of di-t-butyldicarbonate.This procedure works on a wide variety of both electron-rich and electron-deficient aryl amines.
- Kelly, Terence A.,McNeil, Daniel W.
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p. 9003 - 9006
(2007/10/02)
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