- 2-(2-ACRYLOYL-2,6-DIAZASPIRO[3.4]OCTAN-6-YL)-6-(1H-INDAZOL-4-YL)-BENZONITRILE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF G12C MUTANT KRAS PROTEIN FOR INHIBITING TUMOR METASTASIS
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The present invention provides e.g. 2-(2-acryloyl-2,6- diazaspiro[3.4]octan-6-yl)-6-(lH-indazol-4-yl)-benzonitrile and e.g. 2-(2-acryloyl-2,7-diazaspiro[3.5]nonan-7-yl)-6-(1H-indazol-4-yl)- benzonitrile derivatives and related compounds of formula (I) as inhibitors of G12C mutant KRAS protein for treating tumor metastasis. The present description discloses exemplary compounds (e.g. pages 53 to 90; table 1; compounds I-1 to I-141), pharmacological data (e.g. page 125 to 128; table 2; example 1) and synthesis thereof (e.g. pages 129 to 143; examples 2 to 7). Exemplary compounds are e.g. 2-(2-acryloyl-2,6- diazaspiro[3.4]octan-6-yl)-6-(5-methyl-1H-indazol-4-yl)-4- morpholinobenzonitrile (example 2; compound I-1) and 6-(2- acryloyl-2,7-diazaspiro[3.5]nonan-7-yl)-3-methoxy-2-(5-methyl-1H- indazol-4-yl)-4-morpholinobenzonitrile (example 7; compound I-84).
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Page/Page column 137; 138
(2020/05/28)
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- NOVEL THYROMIMETICS
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Compounds are provided having the structure of Formula (I): or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein A, X1, X2, Q, R1, R2 and n are as defined herein. Such compounds function as thyromimetics and have utility for treating diseases such as neurodegenerative disorders and fibrotic diseases. Pharmaceutical compositions containing such compounds are also provided, as are methods of their use and preparation.
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Page/Page column 101-102
(2020/09/19)
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- DERIVATIVES OF SOBETIROME
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Compounds are provided that function as thyromimetics, which compounds have utility for treating diseases such as neurodegenerative disorders. Pharmaceutical compositions containing such compounds are also provided, as are methods of their use and preparation. Such compounds have the structure of Formula (I) as shown herein, or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof.
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Page/Page column 40
(2019/09/04)
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- DERIVATIVES OF SOBETIROME
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Disclosed are halo substituted derivative compounds of sobetirome with improved pharmacological characteristics relative to sobetirome, pharmaceutical compositions that include those compounds and methods of treating diseases such as neurodegenerative dis
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Paragraph 0127
(2017/12/15)
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- Increasing Thyromimetic Potency through Halogen Substitution
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Sobetirome is one of the most studied thyroid hormone receptor β (TRβ)-selective thyromimetics in the field due to its excellent selectivity and potency. A small structural change—replacing the 3,5-dimethyl groups of sobetirome with either chlorine or bro
- Devereaux, Jordan,Ferrara, Skylar J.,Banerji, Tania,Placzek, Andrew T.,Scanlan, Thomas S.
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p. 2459 - 2465
(2016/11/13)
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- CYCLOHEXYLPYRAZOLE-LACTAM DERIVATIVES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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The present invention discloses novel compounds of Formula (I): having 11β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compound
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- OXADIAZOLE- AND OXAZOLE-SUBSTITUTED BENZIMIDAZOLE- AND INDOLE-DERIVATIVES AS DGAT1 INHIBITORS
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The present invention provides oxadiazolyl- substituted benzimidazole- and idole-derivates that are useful for treating conditions or disorders associated with DGAT1 activity in animals, particularly humans.
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Page/Page column 100
(2009/05/29)
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- TETRACYCLIC INHIBITORS OF JANUS KINASES
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The present invention provides compounds that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.
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Page/Page column 106-107
(2008/06/13)
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- INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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The present invention discloses novel compounds of Formula (I): having 11β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11β-HSD type 1 activity.
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Page/Page column 38-39
(2008/06/13)
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- PIERIDINYL SUBSTITUTED PYRROLIDINONES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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ABSTRACT The present invention discloses novel compounds of Formula I: ( I ) having 11-Beta-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11-Beta-HSD type 1 activity. X-17433 PCT -1-
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Page/Page column 41
(2008/06/13)
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- CYCLOHEXYL SUBSTITUTED PYRROLIDINONES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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The present invention discloses novel compounds of Formula I: having 11β -HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11β-HSD type 1 activity.
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Page/Page column 26-27
(2008/06/13)
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- CYCLOHEXYLIMIDAZOLE LACTAM DERIVATIVES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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The present invention discloses novel compounds of Formula I: ( I ) having 11β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds
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Page/Page column 37
(2008/06/13)
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- SUBSTITUTED PYRROLIDINONES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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The present invention discloses novel compounds of Formula I: ( I ) possessing 11β -HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, cognitive disorders, and other conditions associated with 11 β -HSD type 1 activity.
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Page/Page column 28
(2008/06/13)
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- INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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The present invention discloses novel compounds of Formula I: ( I ) possessing 11β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, cognitive disorders, and other conditions associated with 11β-HSD type 1 activity.
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Page/Page column 28-29
(2008/06/13)
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- INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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The present invention discloses novel compounds of Formula I: having 11 Beta-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11Beta-HSD type 1 activity. X-17377
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Page/Page column 38
(2008/06/13)
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- INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
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The present invention discloses novel compounds of Formula I: (I) having 11 -HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11 -HSD type 1 activity.
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Page/Page column 43
(2008/06/13)
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- Novel triarylimidazoles
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Compounds of the general formula (I) are presented and are valuable therapeutics for the treatment of cancer and cancer related diseases.
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Page/Page column 7
(2010/02/11)
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- NOVEL IMIDAZOLE DERIVATIVES AND THEIR USE AS PHARMACEUTICAL AGENTS
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Compounds of the general formula (I) are valuable therapeutics for the treatment of cancer and cancer related diseases.
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Page/Page column 24
(2008/06/13)
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- Simple, short and efficient procedure for the preparation of hydroxyl- and hydroxymethyl-substituted 2,6-dichlorobenzaldehydes
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Hydroxyl- and hydroxymethyl-substituted 2,6-dichlorobenzaldehydes 1-4 have been obtained by lithiation of the corresponding TIPS-protected dichlorophenols or dichlorobenzylic alcohols followed by reaction with DMF and subsequent deprotection of the hydroxy group. Yields are high and formation of regioisomers is not observed.
- Von Hirschheydt, Thomas,Voss, Edgar
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p. 2062 - 2065
(2007/10/03)
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- HYDROXY-BIPHENYL-CARBALDEHYDE OXIME DERIVATIVES AND THEIR USE AS ESTROGENIC AGENTS
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This invention provides estrogen receptor modulators having the structure formula (I): wherein R1 to R6 and R8 are as defined in the specification; or a pharmaceutically acceptable salt thereof.
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Page 18; 36-37
(2008/06/13)
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- ERbeta ligands. Part 1: the discovery of ERbeta selective ligands which embrace the 4-hydroxy-biphenyl template.
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The synthesis and structure-activity relationships of a series of simple biphenyls is described. Optimization of the 4-hydroxy-biphenyl template led to compounds with ERbeta selectivity on the order of 20-70-fold.
- Edsall Jr., Richard J,Harris, Heather A,Manas, Eric S,Mewshaw, Richard E
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p. 3457 - 3474
(2007/10/03)
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- 2-(2,6-dichlorophenyl)-diarylimidazoles
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The invention is directed to compounds of formula (I), which are valuable therapeutics for the treatment of cancer and related diseases.
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Page/Page column 6
(2010/11/29)
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- On the verge of axial chirality: Atroposelective synthesis of the AB-biaryl fragment of vancomycin
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(figure presented) Using the "lactone concept", differently substituted AB-biaryl fragments (P)-2 (R = Me, t-Bu) of vancomycin have been synthesized atroposelectively. Their otherwise configurational instability was remedied by inclusion of two chlorine atoms in the B ring to give (M)-29. Starting from a still configurationally unstable lactone-bridged precursor, we obtained this biaryl with high atroposelectivity (dr 94:6) by ring cleavage with dynamic kinetic diastereomeric resolution.
- Bringmann, Gerhard,Menche, Dirk,Muehlbacher, Joerg,Reichert, Matthias,Saito, Nozomi,Pfeiffer, Steven S.,Lipshutz, Bruce H.
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p. 2833 - 2836
(2007/10/03)
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- BETA-BLOCKING SUBSTITUTED IMIDAZOLES
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Novel substituted imidazoles and methods for their preparation are disclosed. These imidazoles, and their salts, exhibit pharmacological activity which includes antihypertensive activity and β-adrenergic blocking activity.
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- BETA-ADRENERGIC BLOCKING IMIDAZOLYLPHENOXY PROPANOLAMINES
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Substituted imidazoles and methods for their preparation are disclosed. These imidazoles, and their salts, exhibit pharmacological activity which includes antihypertensive activity and β-adrenergic blocking activity. STR1
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- 3-AMINO-2-HYDROXYPROPOXYARYL IMIDAZOLE DERIVATIVES
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Novel substituted imidazoles of the formula STR1 and methods for their preparation are disclosed. These imidazoles, and their salts, exhibit pharmacological activity which includes antihypertensive activity and β-adrenergic blocking activity.
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- Synthesis and Spectroscopic Data of Chlorinated 4-Hydroxybenzaldehydes
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All chlorinated 4-hydroxybenzaldehydes including three hitherto unknown compounds have been synthesized from chlorinated phenols by applying the Reimer-Tiemann method. (1)H NMR, (13)C NMR, and mass-spectral data on all compounds are reported.
- Knuutinen, Juha S.,Kolehmainen, Erkki T.
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p. 139 - 141
(2007/10/02)
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- β-Adrenergic blocking agents with acute antihypertensive activity
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Modification of the pharmacological profile of the vasodilating/β-adrenergic blocking agent 2-[4-[3-(tert-butyl-amino)-2-hydroxypropoxy]phenyl]-4-(trifluoromethyl)imidazole (1) has been investigated. Introduction of selected substitutents onto the imidazo
- Baldwin,Engelhardt,Hirschmann,Lundell,Ponticello,Ludden,Sweet,Scriabine,Share,Hall
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p. 687 - 694
(2007/10/07)
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- 3-AMINO-2-OR-PROPOXYARYL SUBSTITUTED IMIDAZOLES
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Novel 3-amino-2-OR-propoxyaryl substituted imidazoles and methods for their preparation are disclosed. These imidazoles, and their salts, exhibit pharmacological activity which includes antihypertensive activity and β-adrenergic blocking activity.
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