Substituted 1,4-benzodiazepines and uses thereof

The present invention is directed to novel 1,4-benzodiazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have Formula I: or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein: X and Y are independently -C(O)-, -CH₂- or -C(S)-; R¹, R², R³, R⁴, R⁷, R⁸, R^b, R^c, R^d and M are defined herein; R⁵ is hydrogen, alkyl, cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, aminocarbonyl, aminocarbonylalkyl, alkylaminocarbonyl or alkylaminocarbonylalkyl; R⁶ is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; R⁹ is cycloalkyl ...

HETEROARYL LINKED QUINOLINYL MODULATORS OF RORgammat

The present invention comprises compounds of Formula I. 4. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.5. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.6. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.7. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .8. The method of claim 7 , wherein the disease is selected from the group consisting of:inflammatory bowel diseases, rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disorder, psoriatic arthritis, ankylosing spondylitis, neutrophilic asthma, steroid resistant asthma, multiple sclerosis, and systemic lupus erythematosus.9. The method of claim 7 , wherein the disease is psoriasis.10. The method of claim 7 , wherein the disease is rheumatoid arthritis.11. The method of claim 8 , wherein the inflammatory bowel disease is ulcerative colitis.12. The method of claim 8 , wherein the inflammatory bowel disease is Crohn's disease.13. The method of claim 7 , wherein the disease is multiple sclerosis.14. The method of claim 7 , wherein the disease is neutrophilic asthma.15. The method of claim 7 , wherein the disease is steroid resistant asthma.16. The method of claim 7 , wherein the disease is psoriatic arthritis.17. The method of claim 7 , wherein the disease is ankylosing spondylitis.18. The method of claim 7 , wherein the disease is systemic lupus erythematosus.19. The method of claim 7 , wherein the disease is chronic obstructive pulmonary disorder.20. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising administering to the subject an effective amount of a compound of or composition or medicament ...

METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 4. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.5. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.6. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.7. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .8. The method of claim 7 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 7 , rheumatoid arthritis claim 7 , psoriasis claim 7 , chronic obstructive pulmonary disorder claim 7 , psoriatic arthritis claim 7 , ankylosing spondylitis claim 7 , neutrophilic asthma claim 7 , steroid resistant asthma claim 7 , multiple sclerosis claim 7 , and systemic lupus erythematosus9. The method of claim 7 , wherein the disease is psoriasis.10. The method of claim 7 , wherein the disease is rheumatoid arthritis.11. The method of claim 8 , wherein the inflammatory bowel disease is ulcerative colitis.12. The method of claim 8 , wherein the inflammatory bowel disease is Crohn's disease.13. The method of claim 7 , wherein the disease is multiple sclerosis.14. The method of claim 7 , wherein the disease is neutrophilic asthma.15. The method of claim 7 , wherein the disease is steroid resistant asthma.16. The method of claim 7 , wherein the disease is psoriatic arthritis.17. The method of claim 7 , wherein the disease is ankylosing spondylitis.18. The method of claim 7 , wherein the disease is systemic lupus erythematosus.19. The method of claim 7 , wherein the disease is chronic obstructive pulmonary disorder.20. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising administering to ...

ALKYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 5. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.6. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.7. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.8. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .9. The method of claim 12 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 12 , rheumatoid arthritis claim 12 , psoriasis claim 12 , chronic obstructive pulmonary disorder claim 12 , psoriatic arthritis claim 12 , ankylosing spondylitis claim 12 , neutrophilic asthma claim 12 , steroid resistant asthma claim 12 , multiple sclerosis claim 12 , and systemic lupus erythematosus.10. The method of claim 8 , wherein the disease is psoriasis.11. The method of claim 8 , wherein the disease is rheumatoid arthritis.12. The method of claim 9 , wherein the inflammatory bowel disease is ulcerative colitis.13. The method of claim 9 , wherein the inflammatory bowel disease is Crohn's disease.14. The method of claim 8 , wherein the disease is multiple sclerosis.15. The method of claim 8 , wherein the disease is neutrophilic asthma.16. The method of claim 8 , wherein the disease is steroid resistant asthma.17. The method of claim 8 , wherein the disease is psoriatic arthritis.18. The method of claim 8 , wherein the disease is ankylosing spondylitis.19. The method of claim 8 , wherein the disease is systemic lupus erythematosus.20. The method of claim 8 , wherein the disease is chronic obstructive pulmonary disorder.21. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising ...

SECONDARY ALCOHOL QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 6. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.7. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.8. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.9. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .10. The method of claim 9 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 9 , rheumatoid arthritis claim 9 , psoriasis claim 9 , chronic obstructive pulmonary disorder claim 9 , psoriatic arthritis claim 9 , ankylosing spondylitis claim 9 , neutrophilic asthma claim 9 , steroid resistant asthma claim 9 , multiple sclerosis claim 9 , and systemic lupus erythematosus.11. The method of claim 9 , wherein the disease is psoriasis.12. The method of claim 9 , wherein the disease is rheumatoid arthritis.13. The method of claim 10 , wherein the inflammatory bowel disease is ulcerative colitis.14. The method of claim 10 , wherein the inflammatory bowel disease is Crohn's disease.15. The method of claim 9 , wherein the disease is multiple sclerosis.16. The method of claim 9 , wherein the disease is neutrophilic asthma.17. The method of claim 9 , wherein the disease is steroid resistant asthma.18. The method of claim 9 , wherein the disease is psoriatic arthritis.19. The method of claim 9 , wherein the disease is ankylosing spondylitis.20. The method of claim 9 , wherein the disease is systemic lupus erythematosus.21. The method of claim 9 , wherein the disease is chronic obstructive pulmonary disorder.22. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising ...

PHENYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 4. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.5. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.6. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.7. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .8. The method of claim 8 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 8 , rheumatoid arthritis claim 8 , psoriasis claim 8 , chronic obstructive pulmonary disorder claim 8 , psoriatic arthritis claim 8 , ankylosing spondylitis claim 8 , neutrophilic asthma claim 8 , steroid resistant asthma claim 8 , multiple sclerosis claim 8 , and systemic lupus erythematosus.9. The method of claim 7 , wherein the disease is psoriasis.10. The method of claim 7 , wherein the disease is rheumatoid arthritis.11. The method of claim 8 , wherein the inflammatory bowel disease is ulcerative colitis.12. The method of claim 8 , wherein the inflammatory bowel disease is Crohn's disease.13. The method of claim 7 , wherein the disease is multiple sclerosis.14. The method of claim 7 , wherein the disease is neutrophilic asthma.15. The method of claim 7 , wherein the disease is steroid resistant asthma.16. The method of claim 7 , wherein the disease is psoriatic arthritis.17. The method of claim 7 , wherein the disease is ankylosing spondylitis.18. The method of claim 7 , wherein the disease is systemic lupus erythematosus.19. The method of claim 7 , wherein the disease is chronic obstructive pulmonary disorder.20. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising administering ...

QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I.

HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 6. A method of claim 4 , wherein in the compound claim 4 , Ris H.7. The method of claim 1 , wherein the disease is psoriasis.8. The method of claim 1 , wherein the disease is rheumatoid arthritis.9. The method of claim 1 , wherein the inflammatory bowel disease is ulcerative colitis.10. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease.11. The method of claim 1 , wherein the disease is multiple sclerosis.12. The method of claim 1 , wherein the disease is neutrophilic asthma.13. The method of claim 1 , wherein the disease is steroid resistant asthma.14. The method of claim 1 , wherein the disease is psoriatic arthritis.15. The method of claim 1 , wherein the disease is ankylosing spondylitis.16. The method of claim 1 , wherein the disease is systemic lupus erythematosus.17. The method of claim 1 , wherein the disease is chronic obstructive pulmonary disorder. This application is a divisional of U.S. application Ser. No. 14/513,426, filed on Oct. 14, 2014, which claims priority from provisional U.S. Application No. 61/890,889, filed on Oct. 15, 2013, which are all incorporated herein by reference.The invention is directed to substituted quinoline compounds, which are modulators of the nuclear receptor RORγt, pharmaceutical compositions, and methods for use thereof. More particularly, the RORγt modulators are useful for preventing, treating or ameliorating an RORγt mediated inflammatory syndrome, disorder or disease.Retinoic acid-related nuclear receptor gamma t (RORγt) is a nuclear receptor, exclusively expressed in cells of the immune system, and a key transcription factor driving Th17 cell differentiation. Th17 cells are a subset of CD4 T cells, expressing CCR6 on their surface to mediate their migration to sites of inflammation, and dependent on IL-23 stimulation, through the IL-23 receptor, for their maintenance and expansion. Th17 cells produce several proinflammatory ...

ALKYL LINKED QUINOLINYL MODULATORS OF RORγt

The present invention comprises compounds of Formula I. 12-. (canceled)3. The method of claim 17 , wherein the disease is psoriasis.41. The method of claim claim 17 , wherein the disease is rheumatoid arthritis.52. The method of claim claim 17 , wherein the inflammatory bowel disease is ulcerative colitis.62. The method of claim claim 17 , wherein the inflammatory bowel disease is Crohn's disease.71. The method of claim claim 17 , wherein the disease is multiple sclerosis.81. The method of claim claim 17 , wherein the disease is neutrophilic asthma.91. The method of claim claim 17 , wherein the disease is steroid resistant asthma.101. The method of claim claim 17 , wherein the disease is psoriatic arthritis.111. The method of claim claim 17 , wherein the disease is ankylosing spondylitis.121. The method of claim claim 17 , wherein the disease is systemic lupus erythematosus.131. The method of claim claim 17 , wherein the disease is chronic obstructive pulmonary disorder.14. A method of treating or ameliorating a syndrome claim 17 , disorder or disease claim 17 , in a subject in need thereof comprising administering to the subject an effective amount of a compound of or composition or medicament thereof in a combination therapy with one or more anti-inflammatory agents claim 17 , or immunosuppressive agents claim 17 , wherein said syndrome claim 17 , disorder or disease is selected from the group consisting of: rheumatoid arthritis claim 17 , and psoriasis.15. (canceled)20. A method of wherein the disease is selected from the group consisting of: rheumatoid arthritis and psoriasis. This application is a divisional of U.S. application Ser. No. 14/513,455, filed on Oct. 14, 2014, which claims priority from U.S. Application No. 61/890,890, filed on Oct. 15, 2013, each of which is incorporated herein by reference.The invention is directed to substituted quinoline compounds, which are modulators of the nuclear receptor RORγt, pharmaceutical compositions, and methods for ...

PHENYL LINKED QUINOLINYL MODULATORS OF RORgammat

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

SECONDARY ALCOHOL QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. Formula I wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Secondary alcohol quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Methylene linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Heteroaryl linked quinolinyl modulators of RORgammat

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Alkyl linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Phenyl linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Alkyl linked quinolinyl modulators of RORγt

The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Quinolinyl modulators of ror(gamma)t

Secondary alcohol quinolinyl modulators of ror gamma t

The present invention comprises compounds of FormulaI.wherein:R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹are defined in the specification.The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Phenyl linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Quinolinyl modulators of RORγt

The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Alkyl linked quinolinyl modulators of RORyt

The present invention comprises compounds of Formula I. wherein: R

Protease inhibitors

The present invention provides C 1-6 alkyl-4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease; and parasitic diseases, including malaria, by administering to a patient in need thereof one or more compounds of the present invention.

Secondary alcohol quinolinyl modulators of roryt

The present invention comprises compounds of Formula I. Formula I wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR?t activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Phenyl linked quinolinyl modulators of ror-gamma-t

The present invention comprises compounds of Formula I. Formula I wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR?t activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Triazolopyridazine compounds

The invention is directed to triazolopyridazine compounds of Formula I: where R 1 , R 5 , R 6 , R 7 , R 8 , and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

TRIAZOLOPYRIDAZINES AS MODULATORS OF TYROSINE KINASE

La invención está dirigida a compuestos de triazolopiridazinas de la fórmula (I): donde R1, R5, R6, R7, R8, y A son como se definen aquí, el uso de dichos compuestos como moduladores de la proteína de tirosina cinasa, particularmente inhibidores de c-Met, y el uso de tales compuestos para reducir o inhibir la actividad de la cinasa de c-Met en una célula o un sujeto, y modular la expresión c-Met en una célula o sujeto, y el uso de tales compuestos para prevenir o tratar en un sujeto un trastorno de proliferación celular y/o trastornos relacionados con c-Met. La presente invención también esta dirigida a composiciones farmacéuticas que comprenden los compuestos de la presente invención y a métodos para tratar condiciones tales como cánceres y otros trastornos de proliferación celular.

Protease inhibitors

The present invention provides C1-6alkyl-4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease; and parasitic diseases, including malaria, by administering to a patient in need thereof one or more compounds of the present invention.

Peptide deformylase inhibitors

ALKYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR t activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Heteroaryl linked quinolinyl modulators of ror.gamma.t

The present invention comprises compounds of Formula I wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification, The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR?t activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

INHIBITORS OF THE PEPTIDE DESFORMILASA.

Un compuesto de acuerdo con la fórmula (I) o una sal suya farmacéuticamente aceptable en la que: R1 se selecciona del grupo formado por alquilo C1-6, alquil-C1-2-Ar y Ar; R2 se selecciona del grupo formado por hidrógeno, alquilo C1-6, -(CH2)mOH, -(CH2)nAr'', -(CH2)nHet, -Ar'', - SO2R3, -C(O)R3, -C(O)NHR3, -C(O)OR3, -CH(R4)CONR5R6 y - CH(R4)CO2R7; R3 se selecciona del grupo formado por alquilo C1-6, alquil-C1-2-Ar'' y Ar''; R4 es hidrógeno o alquilo C1-6; R5 y R6 se seleccionan independientemente del grupo formado por hidrógeno, alquilo C1-6, alquil-C1-2-Ar'' y Ar''; o R5 y R6 forman juntos un anillo cicloalquílico de cinco o seis miembros que opcionalmente está monosustituido con - CH2OR7; R7 se selecciona del grupo formado por hidrógeno y alquilo C1-3; Ar se selecciona del grupo formado por fenilo, furilo y tienilo, que pueden estar sustituidos todos ellos opcionalmente con uno o más grupos Z1; Ar'' se selecciona del grupo formado por fenilo, naftilo, furilo, piridilo, tienilo, tiazolilo, isotiazolilo, pirazolilo, triazolilo, tetrazolilo, imidazolilo, imidazolidinilo, benzofuranilo, indolilo, tiazolidinilo, isoxazolilo, oxadiazolilo, tiadiazolilo, morfolinilo, piperidinilo, piperazinilo, pirrolilo y pirimidilo, que pueden estar sustituidos todos ellos opcionalmente con uno o más grupos Z2; Het se selecciona del grupo formado por tetrahidrofuranilo y piperidinilo; Z1 se selecciona independientemente del grupo formado por hidrógeno, alquilo C1-3, -CN, F, Cl, Br e I; Z2 se selecciona independientemente del grupo formado por hidrógeno, alquilo C1-6, alcoxi C1-6, -(CH2)nCO2R4, - C(O)NR5R6, -CN, -(CH2)nOH, -NO2, F, Cl, Br, I, -NR5R6 y - NHC(O)R1; m es 2 a 5; y n es 0 a 5. A compound according to formula (I) or a pharmaceutically acceptable salt thereof in which: R1 is selected from the group consisting of C1-6 alkyl, C1-2 alkyl-Ar and Ar; R2 is selected from the group consisting of hydrogen, C1-6 alkyl, - (CH2) mOH, ...

Methods of treatment

Triazolopyridazines as tyrosine kinase modulators.

La invención está dirigida a compuestos de triazolopiridazina de la fórmula (I): (ver fórmula (I) en donde R1, R5, R6, R7, R8, y A son como se define aquí, el uso de dichos compuestos como moduladores de proteína tirosina cinasa, particularmente inhibidores de c-Met, y el uso de dichos compuestos para reducir o inhibir la actividad de cinasa de c-Met en una célula o un sujeto, y modular la expresión de c-Met en una célula o un sujeto, y el uso de dichos compuestos para prevenir o tratar en un sujeto un trastorno proliferativo de células y/o trastornos relacionados con c-Met; la presente invención está dirigida además a composiciones farmacéuticas que comprenden los compuestos de la presente invención y a métodos para tratar condiciones tales como cánceres y otros trastornos proliferativos de células.

Protease inhibitors.

The present invention provides C1-6alkyl-4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease; and parasitic diseases, including malaria, by administering to a patient in need thereof one or more compounds of the present invention.

Protease inhibitors

The present invention provides 4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease, comprising inhibiting said bone loss or excessive cartilage or matrix degradation by administering to a patient in need thereof a compound of the present invention.

Triazolopyridazines as kinase modulators

Protease inhibitors

The present invention provides C1-6alkyl-4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease; and parasitic diseases, including malaria, by administering to a patient in need thereof one or more compounds of the present invention.

Triazolopyridazines as kinase modulators

The invention is directed to triazolopyridazine compounds of Formula I: where R 1 , R 5 , R 6 , R 7 , R 8 , and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

Triazolopyridazines as tyrosine kinase modulators

The invention is directed to triazolopyridazine compounds of Formula (I): where R1, R5, R6, R7, R8, and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

Peptide deformylase inhibitors

PDF inhibitors and novel methods for their use are provided.

Peptid-deformylase-hemmer

Peptide deformylase inhibitors

Novel PDF inhibitors and novel methods for their use are provided.

Inhibidores de proteasas

Inhibidores de proteasas del tipo 4-amino-azepan-3-ona y sus sales , hidratos y solvatos farmacéuticamente aceptables que inhiben proteasas, con inclusión de catepsina K, composiciones farmacéuticas de los compuestos, nuevos compuestos intermedios de los compuestos referidos y métodos para tratar enfermedades de pérdida ósea excesiva o degradación excesiva de cartílago o matriz con inclusión de osteoporosis, enfermedad gingival con inclusión de gengivitis y periodontitis, artritis, más especificamente osteoartritis y artritis reumatoide, enfermedad de Paget, hipercalcemia de carácter maligno, y enfermedad metabólica ósea, que comprende inhibir dicha pérdida ósea com degradación excesiva de cartílago o matriz por administración de un compuesto de la presente invención a un paciente que se encuentra en necesidad de eelo.

Peptiddeformylase-hemmer

4-amino-azepan-3-one derivatives as protease inhibitors and a method for obtaining thereof