BICYCLIC SULFONAMIDE COMPOUNDS AS SODIUM CHANNEL INHIBITORS

The present invention provides compounds of Formula I, 132-. (canceled)34. The compound in accordance with claim 33 , or a pharmaceutically acceptable salt thereof claim 33 , wherein each Ris independently H claim 33 , F or Cl.35. The compound in accordance with claim 33 , or a pharmaceutically acceptable salt thereof claim 33 , wherein Ris a 6 membered aryl or heteroaryl group claim 33 , where the heteroaryl group can have from 1 to 3 heteroatoms independently selected from O claim 33 , N or S claim 33 , and the aryl or heteroaryl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo claim 33 , —Calkyl claim 33 , —OCalkyl claim 33 , hydroxyCalkyl claim 33 , —CF claim 33 , —CHF claim 33 , —CHF claim 33 , —OCF claim 33 , —OCHF claim 33 , —OCHF claim 33 , CN claim 33 , —C(═O)NRR claim 33 , —C(═O)OR claim 33 , —OA or A; and{'sub': 1-6', '1-6', '1-6', '3', '2', '2', '3', '2', '2, 'sup': b', 'b, 'A is a 5 to 6 membered aryl or heteroaryl group, wherein the heteroaryl group can have from 1 to 3 heteroatoms independently selected from O, N or S, and the aryl or heteroaryl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —Calkyl, —OCalkyl, hydroxyCalkyl —CF, —CHF, —CHF, —OCF, —OCHF, —OCHF, —CN, or —C(═O)NRR.'}36. The compound in accordance with claim 33 , or a pharmaceutically acceptable salt thereof claim 33 , wherein Ris a phenyl ring or pyridyl ring claim 33 , wherein the ring can be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo claim 33 , —Calkyl claim 33 , —OCalkyl claim 33 , hydroxyCalkyl claim 33 , —CF claim 33 , —CHF claim 33 , —CHF claim 33 , —OCF claim 33 , —OCHF claim 33 , —OCHF claim 33 , CN claim 33 , —C(═O)NRR claim 33 , —C(═O)OR claim 33 , —OA or A.37. The compound in accordance with claim 33 , or a pharmaceutically acceptable salt thereof claim 33 , wherein A is a ring selected from cyclopropyl claim 33 , ...

Pyridine sulfonamides

The present invention provides compounds of Formula (I), as defined in the specification, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders, cough, or itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

COUPON AND CONTEST BUSINESS METHODS

A coupon and/or contest business method is described. Users can be given the opportunity to obtain and use a coupon that provides benefits such as discounts at a multitude of different stores. The users can also be entered into one or more contests. For instance, in one embodiment, the user is automatically entered into a first contest via use of the coupon, and can enter a second contest for a nominal fee, such as a fee of $0.25 /month. Periodic prizes, such as monthly giveaways, can be included. 1. A business method for providing discounts , comprising providing a user with a digital coupon usable at a plurality of stores to provide the user with a discount , further comprising entering the user into a contest after the user downloads or uses the digital coupon.2. The business method of claim 1 , wherein the digital coupon is provided via text message.3. The business method of claim 1 , wherein the digital coupon is provided via download of an app.4. The business method of claim 3 , wherein the app permits a user to become a character in a movie or show using facial recognition technology.5. The business method of claim 1 , further comprising asking the user one or more questions.6. The business method of claim 5 , wherein the user is provided a benefit if they answer one of said questions correctly.7. The business method of claim 1 , wherein the digital coupon provides at least a 10% discount.8. The business method of claim 1 , where the digital coupon provides at least a 25% discount online.9. A business method claim 1 , comprising:providing a website;contacting at least one user to provide the address of said website; providing said user with a coupon for use at a plurality of stores; and', 'entering said user into a first contest with a first prize., 'upon said user visiting said website and entering information10. The business method of claim 9 , wherein said contacting comprises contacting said user via ringless voicemail.11. The business method of claim 10 ...

BICYCLIC SULFONAMIDE COMPOUNDS AS SODIUM CHANNEL INHIBITORS

The present invention provides compounds of Formula I, 2. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Aand Ais claim 1 , independently claim 1 , CR.3. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently H or F.4. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', 'b', 'b', 'b', '1, 'sub': 1-6', '1-6', '1-6', '3', '2', '2', '3', '2', '2, 'Ris a ring selected from phenyl, pyridinyl or pyrimidinyl, wherein the ring is substituted with from 1 to 4 substituents independently selected from halo, —Calkyl, —OCalkyl, hydroxyCalkyl, —CF, —CHF, —CHF, —OCF, —OCHF, —OCHF, CN, —C(═O)NRR, —C(═O)OR, —OA or A, provided at least one substituent on Ris A or —OA; and'}{'sub': 1-6', '1-6', '1-6', '3', '2', '2', '3', '2', '2, 'sup': b', 'b, 'A is a 5 to 6 membered aryl or heteroaryl group, or a 4 to 6 membered N-linked heterocycloalkyl group, or a 3 to 6 membered cycloalkyl group, where the heteroaryl can have from 1 to 3 heteroatoms independently selected from O, N or S, the N-linked heterocycloalkyl can have 1 additional heteroatom independently selected from O, N or S, and the aryl, heteroaryl, heterocyclic and cycloalkyl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —Calkyl, —OCalkyl, hydroxyCalkyl —CF, —CHF, —CHF, —OCF, —OCHF, —OCHF, —CN, or —C(═O)NRR.'}5. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a phenyl ring or pyridyl ring claim 1 , wherein the ring is substituted with from 1 to 4 substituents independently selected from halo claim 1 , —Calkyl claim 1 , —OCalkyl claim 1 , hydroxyCalkyl claim 1 , —CF claim 1 , —CHF claim 1 , —CHF claim 1 , —OCF claim 1 , —OCHF claim 1 , —OCHF claim 1 , CN claim 1 , —C(═O)NRR—C(═O)OR claim 1 , —OA or A claim 1 , provided ...

Novel prmt5 inhibitors

Described herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, such as cancer, metabolic and blood disorders. Compounds of Formula (I) have the following structure of Formule (I).

Novel prmt5 inhibitors

Described herein are compounds of Formula I and pharmaceutically acceptable salt thereof, stereoisomers, tautomers as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure: (I)

Tricyclic carboxamide derivatives as prmt5 inhibitors

Described herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, such as cancer, metabolic and blood disorders. Compounds of Formula (I) have the following structure of Formula (I).

Inhibidores de prmt5 novedosos

Se describen en el presente documento compuestos de Fórmula I y sales farmacéuticamente aceptables de los mismos, así como composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, tales como cáncer, trastornos metabólicos y sanguíneos. Los compuestos de Fórmula I tienen la siguiente estructura:

Inhibidores de prmt5 novedosos

Described herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, such as cancer, metabolic and blood disorders. Compounds of Formula (I) have the following structure of Formule (I).

Derivados de carboxamida tricíclica como inhibidores de prmt5

Se describen en el presente documento compuestos de Fórmula I y sales farmacéuticamente aceptables de los mismos, así como composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, tales como cáncer, trastornos metabólicos y sanguíneos. Los compuestos de Fórmula I tienen la siguiente estructura:

Inhibidores de prmt5

Se describen en el presente documento inhibidores novedosos de PRMT5 de Fórmula I y sales farmacéuticamente aceptables de los mismos, así como composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, metabólicos y sanguíneos. Los compuestos de Fórmula I tienen la siguiente estructura:

Inhibidores de prmt5

Se describen en el presente documento inhibidores novedosos de PRMT5 de Fórmula I y sales farmacéuticamente aceptables de los mismos, así como composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, metabólicos y sanguíneos. Los compuestos de Fórmula I tienen la siguiente estructura:

PRMT5 inhibitors

Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:

Inhibidores de prmt5 novedosos.

Se describen en el presente documento compuestos de fórmula I y sales farmacéuticamente aceptables de los mismos, estereoisómeros, tautómeros así como composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, metabólicos y sanguíneos. Los compuestos de fórmula I tienen la siguiente estructura: (I) (Ver Fórmula I).

Inhibidores de prmt5.

Se describen en el presente documento inhibidores novedosos de PRMT5 de Fórmula I y sales farmacéuticamente aceptables de los mismos, así como composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, metabólicos y sanguíneos. Los compuestos de Fórmula I tienen la siguiente estructura: (ver Fórmula).

Tricyclic carboxamide derivatives as prmt5 inhibitors

Described herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, such as cancer, metabolic and blood disorders. Compounds of Formula (I) have the following structure of Formule (I).

Novel PRMT5 inhibitors

Described herein are compounds of Formula I and pharmaceutically acceptable salt thereof, stereoisomers, tautomers as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure: (I)

Novel prmt5 inhibitors

Described herein are compounds of Formula I and pharmaceutically acceptable salt thereof, stereoisomers, tautomers as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure: (I)

Derivados triciclicos de carboxamida como inhibidores de la prmt5

Referido a un compuesto de Formula I, un tautomero del mismo, un esteroisomero del mismo o una sal farmaceuticamente aceptable de cualquiera de los anteriores, en donde: R es un triciclo independientemente seleccionado de las formulas IA y IB, en donde la linea punteada es un enlace sencillo o doble; X1, X2, X6 y X7 son en cada caso N o C, en donde tanto X1 como X2 no pueden ser N al mismo tiempo, y en donde si X1 es C, puede estar opcionalmente sustituido con halo; X3, X4 y X5 se seleccionan en cada caso independientemente de un C, O, N y S opcionalmente sustituidos; R3 en cada caso se selecciona independientemente de H o alquilo C1-3; Ar1 es un arilo o heteroarilo opcionalmente sustituido de seis miembros; R1 en cada caso se selecciona independientemente de H, halo, alquilo C1-3 opcionalmente sustituido; entre otros; R2 en cada caso se selecciona independientemente de un alquilo C1-8 opcionalmente sustituido, ciclo o heterociclo de 5 o 6 miembros opcionalmente sustituido con hidroxi, amino, entre otros. Un compuesto seleccionado es 4-amino-N-(ciclopropilmetil)-N-((5-(trifluorometil)-2-piridinil)metil)-1,3-dihidrofuro[3,4-c]quinolin-8-carboxamida. Estos compuestos son derivados triciclicos de carboxamida, y son inhibidores de la PRMT5. Tambien se refiere a metodos de sintesis de dichos compuestos, productos intermedios, composiciones farmaceuticas que comprenden dichos compuestos, y su uso en el tratamiento de trastornos proliferativos, tales como cancer, trastornos metabolicos y sanguineos.

Inhibidores de prmt5 novedosos.

Se describen en el presente documento compuestos de Fórmula I y sales farmacéuticamente aceptables de los mismos, así como composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, tales como cáncer, trastornos metabólicos y sanguíneos. Los compuestos de Fórmula I tienen la siguiente estructura: (ver Fórmula).

Tricyclic-amido-bicyclic prmt5 inhibitors

Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:

Tricyclic-amido-bicyclic prmt5 inhibitors

Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:

Tricyclic-amido-bicyclic prmt5 inhibitors

Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:

Heterocyclic inhibitors of kras g12c mutant proteins and uses thereof

The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic, and colorectal cancer. In particular, the disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein the substituents are as described.

Inhibidores tricíclicos-amido-bicíclicos de prmt5.

Se describen en el presente documento inhibidores novedosos de PRMT5 de Fórmula I y sales farmacéuticamente aceptables de los mismos, así como las composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, metabólicos y sanguíneos. Los compuestos de fórmula I tienen la siguiente estructura (ver fórmula).

Heterocyclic inhibitors of kras g12c mutant proteins and uses thereof

The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic, and colorectal cancer. In particular, the disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein the substituents are as described.

Novel prmt5 inhibitors

Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:

Inhibidores de prmt5

Un compuesto de Formula I, en donde R1 , R2 y el atomo de nitrogeno al que estan unidos forman un anillo de cinco, seis o siete miembros que puede estar saturado o parcialmente saturado, y comprende 0, 1 o 2 heteroatomos adicionales, iguales o diferentes seleccionados de O, N o S, en donde el atomo de S esta opcionalmente sustituido con uno o dos grupos oxo; en donde el anillo formado por R1 , R2 y el atomo de nitrogeno al que estan unidos puede estar sustituido con 0, 1, 2 o 3 R3 ; en donde R3 se selecciona en cada caso de alquilo C1-6 , halo, haloalquilo C1-6 , -O-alquilo C1-6 , -O-haloalquilo C1-6 , -C(O)-alquilo C1-6 , -C(O)-haloalquilo C1-6 , -C(O)O-alquilo C1-6 , -C(O)Ohaloalquilo C1-6 y ciclo de cinco o seis miembros que puede estar saturado, parcialmente saturado o ser aromatico, y comprende 0, 1 o 2 heteroatomos, iguales o diferentes, seleccionados de O, N y S, en donde el ciclo puede estar opcionalmente sustituido con uno o mas Ra , en donde Ra se selecciona en cada caso de halo, CN, alquilo C1-6 , haloalquilo C1-6 , pentafluorosulfanilo, -O-alquilo C1-3 y -O-haloalquilo C1-3; en donde R es un triciclo seleccionado de las formulas IA y IB; X1 , X2 , X6 , X7 y X8 se seleccionan en cada caso de N y C opcionalmente sustituidos, en donde los sustituyentes se seleccionan de alquilo C1-3; en donde tanto X1 como X2 no pueden ser N al mismo tiempo, y X6 y X7 , y X7 y X8 no pueden ser N al mismo tiempo; ademas en donde si X1 es C, puede estar opcionalmente sustituido con halo; X3 , X4 y X5 se seleccionan en cada caso de C, O, N y S opcionalmente sustituidos, en donde los sustituyentes se seleccionan de alquilo C1-3 y alquil C1-3 (OH), en donde el alquilo puede estar opcionalmente sustituido con halo. Son compuestos preferidos: (4-amino-1-metil-1H-pirazolo[4,3-c][1,7]naftiridin-8-il)((3S)-3-(4-(trifluorometil)fenil)-4- morfolinil)metanona; (4-amino-1,3-dihidrofuro[3,4-c][1,7]naftiridin-8-il)((3S,5R)-3-(6-(ciclopropiloxi)-3- piridazinil)-5-metil-4-morfolinil)metanona ...

Inhibidores de prmt5 novedosos

Se describen en el presente documento compuestos de fórmula (1) y sales farmacéuticamente aceptables de los mismos, así como composiciones farmacéuticas de los mismos. Los compuestos de la presente invención son útiles para inhibir la actividad de PRMT5 y pueden tener uso en el tratamiento de trastornos proliferativos, metabólicos y sanguíneos. Los compuestos de fórmula (1) tienen la siguiente estructura. Reivindicación 1: Un compuesto de fórmula (1), un tautómero del mismo, un esteroisómero del mismo o una sal farmacéuticamente aceptable de cualquiera de los anteriores: en donde R¹, R² y el átomo de nitrógeno al que están unidos forman un anillo de cinco, seis o siete miembros que puede estar saturado o parcialmente saturado, y comprende 0, 1 ó 2 heteroátomos adicionales, iguales o diferentes, seleccionados de O, N o S, en donde el átomo de S está opcionalmente sustituido con uno o dos grupos oxo; en donde el anillo formado por R¹, R² y el átomo de nitrógeno al que están unidos puede estar sustituido con 0, 1, 2 o R³; en donde R³ se selecciona en cada caso de alquilo C₁₋₆, halo, haloalquilo C₁₋₆, -O-alquilo C₁₋₆, -O-haloalquilo C₁₋₆, -C(O)-alquilo C₁₋₆, -C(O)-haloalquilo C₁₋₆, -C(O)O-alquilo C₁₋₆, -C(O)O-haloalquilo C₁₋₆ y ciclo de cinco o seis miembros que puede estar saturado, parcialmente saturado o ser aromático, y comprende 0, 1 ó 2 heteroátomos, iguales o diferentes, seleccionados de O, N y S, en donde el ciclo puede estar opcionalmente sustituido con uno o más Rᵃ, en donde Rᵃ se selecciona en cada caso de halo, CN, alquilo C₁₋₆, haloalquilo C₁₋₆, pentafluorosulfanilo, -O-alquilo C₁₋₃ y -O-haloalquilo C₁₋₃; en donde R es un triciclo seleccionado de las fórmulas (2) y (3), en donde ⁻ ⁻ ⁻ ⁻ ⁻ es un enlace sencillo o doble, X¹, X², X⁶, X⁷ y X⁸ se seleccionan en cada caso de N y C opcionalmente sustituidos, en donde los sustituyentes se seleccionan de alquilo C₁₋₃; en donde tanto X¹ como X² no pueden ser N al mismo tiempo, y X⁶ y X⁷ y X⁷ y X⁸ no pueden ser N al ...

Prmts inhibitors

Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:

Tricyclic carboxamide derivatives as prmt5 inhibitors

Described herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, such as cancer, metabolic and blood disorders. Compounds of Formula (I) have the following structure of Formule (I).

Universal connection for piston rods

Biaryl derivatives and related uses

The present disclosure relates to compounds of Formula (I), and to their prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for modulating DNA polymerase Q activity and may be used in the treatment of disorders in which DNA polymerase Q activity is implicated, such as cancer.

PRMT5 inhibitors

Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:

Semi-saturated bicyclic derivatives and related uses

The present disclosure relates to compounds of Formula (I): and to their prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for modulating DNA polymerase Θ activity and may be used in the treatment of disorders in which DNA polymerase Θ activity is implicated, such as cancer.

Bicyclic sulfonamide compounds as sodium channel inhibitors

The present invention provides compounds of Formula I, and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.