HETEROBICYCLO-SUBSTITUTED [1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-5-AMINE COMPOUNDS WITH A2A ANTAGONIST PROPERTIES

Disclosed are compounds of Formula G1: where “R G3 ”. “R d1 ” to “R d4 ”, “n”, “m”, “p”, “W”, “X”, “Y”, and “Z” are defined herein, which compounds are antagonists of A 2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A 2A receptor in the potential treatment or prevention of neurological disorders and diseases in which A 2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions.

Heterocyclic-substituted benzofuran derivatives and methods of use thereof for the treatment of viral diseases

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis C

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Heterocyclic compounds and methods of use thereof for the treatment of hepatitis C

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.(I)

Piperazine derivatives as HIV protease inhibitors

The present invention is directed to piperazine derivatives, pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.

Piperazine-substituted [1,2,4]triazolo[1,5-C]quinazolin-5-amine compounds with A2A antagonist properties

Disclosed are compounds of Formula A: (structurally represented) where “RG1”, “RG2a”, “RG4”, “RG5”, “MG1”, “n” and “m” are defined herein which compounds are antagonists of A2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A2a receptor in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions.

BICYCLIC COMPOUNDS AS INHIBITORS OF DIACYGLYCEROL ACYLTRANSFERASE

The present invention relates to novel heterocyclic compounds as diacylglycerol acyltransferase (“DGAT”) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the invention is shown below (I). 112-. (canceled)14. A pharmaceutical composition comprising at least one compound of and at least one pharmaceutically acceptable carrier.15. A method of inhibiting DGAT1 in a patient in need thereof comprising administering therapeutically effective amounts of at least one compound of to said patient.16. A method of treating obesity claim 13 , diabetes or metabolic syndrome in a patient in need thereof comprising administering therapeutically effective amounts of at least one compound of to said patient.19. A pharmaceutical composition comprising at least one compound of and at least one pharmaceutically acceptable carrier.20. A method of inhibiting DGAT1 in a patient in need thereof comprising administering therapeutically effective amounts of at least one compound of to said patient.21. A method of treating obesity claim 18 , diabetes or metabolic syndrome in a patient in need thereof comprising administering therapeutically effective amounts of at least one compound of to said patient. The present invention relates to certain heterocyclic compounds useful as diacylglycerol acyltransferase (“DGAT”) inhibitors, especially diacylglycerol acyltransferase 1 (“DGAT1”) inhibitors, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat or prevent various diseases including cardiovascular disease, dyslipidemia, obesity and diabetes (e.g., Type 2 diabetes).There is a need for additional ways of treating diseases ...

HETEROCYCLIC-SUBSTITUTED BENZOFURAN DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. 2. The compound of claim 1 , wherein Ris —N(CH)SOCH.3. The compound of claim 1 , wherein A is pyridyl claim 1 , pyridazinyl claim 1 , pyrimidinyl claim 1 , thiophenyl or pyrazinyl claim 1 , each of which can be optionally substituted as set forth in .4. The compound of claim 1 , wherein B is an 8-membered bicyclic heteroaryl group claim 1 , which can be optionally substituted as set forth in .5. The compound of claim 1 , wherein B is a 9-membered bicyclic heteroaryl group claim 1 , which can be optionally substituted as set forth in .6. The compound of claim 1 , wherein B is a 10-membered bicyclic heteroaryl group claim 1 , which can be optionally substituted as set forth in .7. The compound of claim 1 , wherein A is pyridyl or pyrazinyl claim 1 , each of which can be optionally substituted with halo or a —O—(C-Calkyl) group claim 1 , and B is selected from indolyl claim 1 , benzoxazolyl or oxazolo[4 claim 1 ,5-b]pyridinyl claim 1 , each of which can be optionally substituted with a halo group.10. The compound of which is selected from the compounds numbered 1-297 in the above specification claim 1 , or a pharmaceutically acceptable salt thereof.11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.12. The pharmaceutical composition of claim 11 , further comprising a second therapeutic agent selected from the group consisting of HCV antiviral agents claim 11 , immunomodulators claim 11 , and anti-infective agents.13. The pharmaceutical composition of claim 12 , wherein the second ...

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of viral diseases

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

SUBSTITUTED BENZOFURAN COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R claim 1 , Rand Rare methyl.32. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , claim 2 , wherein D is N(CH)SOCH.43. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , claim 3 , wherein each halo is F.5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein B is —CH—Ar claim 4 , —CHCH—Ar claim 4 , —CH(CH)—Ar claim 4 , or —C(CH)—Ar.8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein Ris hydrogen or methyl and Ris hydrogen.9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein B ishydrogen;phenyl;fluorophenyl;{'sub': 2', '1-2, '—(CH)-phenyl;'}{'sub': '2', '—CH-fluorophenyl;'}{'sub': '3', '—CH(CH)-fluorophenyl;'}{'sub': 3', '2, '—C(CH)-fluorophenyl;'}{'sub': '2', '—CH-chlorophenyl;'}{'sub': 2', '3, '—CH-phenyl-OCH;'}{'sub': '2', '—CH-phenyl-cyano;'}{'sub': '2', '—CH-fluoropyridine;'}thiophene;cyclopropyl;{'sub': 2', '3, '—CH(CHOCH)-fluorophenyl;'}{'sub': '2', '—CH(CHOH)-phenyl;'}{'sub': '2', '—CH(CHOH)-fluorophenyl;'}{'sub': 2', '2, '—CH(CHCHOH)-fluorophenyl;'}{'sub': '2', '—CH-4-fluoro-2-methoxyphenyl; or'}{'sub': '2', '—CH-difluorophenyl.'}11. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an effective amount of the compound of or a pharmaceutically acceptable salt thereof.12. The pharmaceutical composition of claim 11 , further comprising a second therapeutic agent selected from the group ...

DIMERIC COMPOUNDS

The present invention provides a compound of formula I which act as inhibitors of SMAC protein binding to Inhibitor of Apoptosis Proteins (IAPs), and/or inhibitors of activated caspase protein binding to IAPs (I) their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances, alone or in combination with DR5/FAP agonist antibodies. The active compound of the present invention is useful in the amelioration, treatment or control of cancer, especially solid tumors. 2. The compound according to claim 1 , wherein Ris F.4. The compound according to claim 1 , wherein A is A-2 and Ris F or wherein A is A-4 and Ris F.5. The compound according to claim 1 , wherein L is L-1 claim 1 , L-2 claim 1 , or L-3.6. The compound according to claim 1 , wherein L is L-4 or L-6.7. The compound according to claim 1 , wherein L is L-5 and k is 3.8. The compound according to claim 1 , selected from the group consisting of:N—((S)-3-((2,6-difluorophenyl)carbamoyl)-2-((S)-2-((S)-2-(methylamino)propanamido)-2-(tetrahydro-2H-pyran-4-yl)acetyl)isoindolin-5-yl)-6-(4-fluorobenzyl)-3-methyl-1-(2-((2R,5R)-5-methyl-2-(((R)-3-methylmorpholino)methyl)piperazin-1-yl)acetyl)indoline-3-carboxamide trihydrochloride,(3R)—N-[2-[[(3S)-3-[(2,6-difluorophenyl)carbamoyl]-2-[(2S)-2-[[(2 S)-2-(methylamino)propanoyl]amino]-2-(oxan-4-yl)acetyl]-1,3-dihydroisoindol-5-yl]amino]-2-oxoethyl]-6-[(4-fluorophenyl)methyl]-3-methyl-1-[2-[(2R,5R)-5-methyl-2-[[(3R)-3-methylmorpholin-4-yl]ethyl]piperazin-1-yl]acetyl]-2H-indole-3-carboxamide trihydrochloride,(3S)—N-[2-[[(3S)-3-[(2,6-difluorophenyl)carbamoyl]-2-[(2 S)-2 [[(2 S)-2-(methylamino)propanoyl]amino]-2-(oxan-4-yl)acetyl]-1,3-dihydroisoindol-5-yl]amino]-2-oxoethyl]-6-[(4-fluorophenyl)methyl]-3-methyl-1-[2-[(2R,5R)-5-methyl-2-[[(3R)-3-methylmorpholin-4-yl]methyl]piperazin-1-yl]acetyl]-2H-indole-3-carboxamide trihydrochloride,(3 S)-2-[(2 S)-3,3-dimethyl-2-[[(2 S)-2-(methylamino)propanoyl]amino]butanoyl]-7-[[2-[[(3 S)-6-[(4- ...

HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF HEPATITIS C

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.(I) 3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein R claim 2 , Rand Rare methyl.4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein D is N(CH)SOCH.5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein each halo is F.8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein B is Ar claim 7 , —C(O)—Ar claim 7 , or —SO—Ar; wherein Ar is a 9-membered bicyclic ring with 1 claim 7 , 2 claim 7 , or 3 heteroatom ring atoms selected from N claim 7 , O and S claim 7 , optionally substituted with 1 claim 7 , 2 or 3 substituents independently selected from C-Calkyl claim 7 , C-Calkoxy claim 7 , F claim 7 , CF claim 7 , and cyano.10. The compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein B is —SO—Ar claim 7 , —SOCH—Ar claim 7 , —SOCHCH—Ar claim 7 , —C(O)—Ar; or —C(O)CH—Ar; wherein Ar is phenyl claim 7 , methylphenyl claim 7 , fluorophenyl claim 7 , difluorophenyl claim 7 , pyridine claim 7 , or fluoropyridine.13. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an effective amount of the compound of or a pharmaceutically acceptable salt thereof.14. The pharmaceutical composition of claim 13 , further comprising a second therapeutic agent selected from the group consisting of HCV antiviral agents claim 13 , immunomodulators claim 13 , and anti-infective agents.15. The pharmaceutical composition of claim 14 , wherein the second therapeutic agent is selected from the group consisting of HCV ...

PIPERAZINE DERIVATIVES AS HIV PROTEASE INHIBITORS

The present invention is directed to piperazine derivatives, pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. 6. The compound according to wherein Q is —S(O)—.7. The compound according to wherein Q is —C(O)—.10. The compound according to wherein X is selected from: H claim 9 , —OH claim 9 , —NHand —N(H)—C(O)—OCalkyl.12. The compound according to wherein Zis Calkyl claim 1 , optionally substituted with 1 to 3 fluoro groups.1314-. (canceled)15. The compound according to wherein Zis phenyl or benzyl claim 1 , each optionally substituted with 1 to 3 substituents independently selected from methyl claim 1 , formyl claim 1 , —CF claim 1 , —OCF claim 1 , —N(H) claim 1 , —N(H)(Calkyl) claim 1 , —N(Calkyl) claim 1 , —N(H)—S(O)—Calkyl claim 1 , —C(O)—O—Calkyl and —S(O)—Calkyl claim 1 , wherein each Calkyl in the aforementioned list is optionally substituted with 1 to 3 halo groups.16. The compound according to wherein Zis Ccycloalkyl or Ccycloalkyl-methyl.1718-. (canceled)19. The compound according to wherein Zis HetA selected from pyridine claim 1 , pyrrole claim 1 , furan claim 1 , thiophene claim 1 , pyrazole claim 1 , imidazole claim 1 , thiazole claim 1 , oxazole claim 1 , isoxazole claim 1 , pyrazine claim 1 , pyrimidine claim 1 , pyrdazine claim 1 , triazole claim 1 , oxadiazole claim 1 , thiadiazole claim 1 , dithiazole claim 1 , or a benzo analog of any of the foregoing claim 1 , each optionally substituted with 1 to 3 substituents independently selected from methyl claim 1 , formyl claim 1 , —CF claim 1 , —OCF claim 1 , —N(H) claim 1 , —N(H)(Calkyl) claim 1 , —N(Calkyl) claim 1 , —N(H)—C(O)—Calkyl claim 1 , —N(H)—S(O)—Calkyl claim 1 , —C(O)—O—Calkyl and —S(O)—Calkyl claim 1 , wherein each Calkyl in the aforementioned list is optionally ...

PIPERAZINE-SUBSTITUTED [1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-5-AMINE COMPOUNDS WITH A2A ANTAGONIST PROPERTIES

Disclosed are compounds of Formula A: (structurally represented) where “RG1”, “RG2a”, “RG4”, “RG5”, “MG1”, “n” and “m” are defined herein which compounds are antagonists of A2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A2a receptor in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions. 11. A method of treating a central nervous system disease by administering a compound of .12. A pharmaceutical composition that comprises an inert carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.13. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , for use in medicine.14. Use of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , for the manufacture of a medicament for the treatment or prevention of a central nervous system disorder.15. A method of treating a central nervous system disorder in a mammalian patient in need thereof by administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.16. The method of wherein said central nervous system disorder is a movement disorder associated with Parkinson's disease or the treatment thereof using dopaminergic therapy. The present application claims the benefit of PCT International patent application serial no. PCT/CN2012/087851, filed Dec. 28, 2012, hereby incorporated by reference herein.Adenosine is known to be an endogenous modulator of a number of physiological functions. At the cardiovascular system level, adenosine is a strong vasodilator and a cardiac depressor. On the central nervous system, adenosine induces sedative, anxiolytic and antiepileptic effects. On the respiratory system, adenosine induces bronchoconstriction. At the kidney level, ...

HETEROBICYCLO-SUBSTITUTED [1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-5-AMINE COMPOUNDS WITH A2A ANTAGONIST PROPERTIES

Disclosed are compounds of Formula G1 (structurally represented): where “RG3” “Rd1” to “Rd4”, “n”, “m”, “p”, “W”, “X”, “Y”, and “Z” are defined herein which compounds are antagonists of A2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A2a receptor in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions. 3. A compound of or a pharmaceutically acceptable salt thereof wherein claim 1 , when X claim 1 , Y claim 1 , or Z is —C(R)═ claim 1 , and Ris selected to be a halogen substituted C-alkyl moiety claim 1 , the halogen is F or Cl.4. A compound of or a pharmaceutically acceptable salt thereof wherein at least one of X claim 1 , Y claim 1 , or Z is —N═ claim 1 , and at least one of X claim 1 , Y claim 1 , or Z is —O— or —S—.12. A compound of wherein Ris —CH(CH)—CH—; —CH—CH—; or —CH—.13. A compound which is:7-methoxy-2-(2-(3-(methylthio)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)ethyl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine;7-(2-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)ethyl)-N-tert-butyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine-3-carboxamide;2-(2-(3-bromo-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)ethyl)-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine;ethyl 7-(2-(5-amino-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-2-yl)ethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine-3-carboxylate;2-(2-(2-chloro-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)ethyl)-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine;2-(2-(4-bromo-5,6-dihydro-1,7-naphthyridin-7(8H)-yl)ethyl)-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine;2-(2-(1-cyclopropyl-6,7-dihydro-1H-pyrazolo[4,3-c]pyridin-5(4H)-yl)ethyl)-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine;2-(2-(3-isopropyl-5,6-dihydroimidazo[1,5-a]pyrazin-7(8H)-yl)ethyl)- ...

TETRACYCLIC HETEROCYCLE COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF HEPATITIS C

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. 2. The compound of claim 1 , wherein Rand Rare C-Calkyl.3. The compound of claim 2 , wherein R claim 2 , Rand Rare methyl.4. The compound of claim 3 , wherein one of Rand Ris hydrogen.5. The compound of claim 3 , wherein Ris F.8. The compound of claim 6 , wherein A is C-Ccycloalkyl claim 6 , or a 5-6 membered aromatic monocyclic ring with 0 claim 6 , 1 claim 6 , 2 or 3 heteroatom ring atoms selected from N and S claim 6 , optionally substituted with 1 or 2 substituents independently selected from C-Calkyl claim 6 , C-Calkoxy claim 6 , C-Chaloalkyl claim 6 , oxo claim 6 , halo claim 6 , and —O—C-Chaloalkyl.13. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an effective amount of the compound of or a pharmaceutically acceptable salt thereof.14. The pharmaceutical composition of claim 13 , further comprising a second therapeutic agent selected from the group consisting of HCV antiviral agents claim 13 , immunomodulators claim 13 , and anti-infective agents.15. The pharmaceutical composition of claim 14 , wherein the second therapeutic agent is selected from the group consisting of HCV NS3 and NS3/4A protease inhibitors claim 14 , HCV NS5A inhibitors and HCV NS5B polymerase inhibitors.1617-. (canceled)18. A method of treating a patient infected with HCV claim 1 , the method comprising administering to the patient the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , in an amount effective to prevent and/or treat infection by HCV in the patient.19. The method of claim 18 , further comprising administering to said patient an effective amount ...

TETRACYCLIC HETEROCYCLE COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF HEPATITIS C

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. I 2. The compound of claim 1 , wherein Rand Rare independently C-Calkyl.3. The compound of claim 2 , wherein R claim 2 , Rand Rare methyl.4. The compound of claim 3 , wherein two or three of R claim 3 , Rand Rare hydrogen.5. The compound of claim 4 , wherein each halo is F.7. The compound of claim 4 , wherein A is{'sub': 3', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'C-Ccycloalkyl, or a 5-6 membered aromatic monocyclic ring with 0, 1, 2 or 3 heteroatom ring atoms independently selected from N and S, optionally substituted with 1 or 2 substituents independently selected from C-Calkyl, C-Calkoxy, C-Chaloalkyl, oxo, halo, and —O—C-Chaloalkyl.'}14. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) an effective amount of the compound of or a pharmaceutically acceptable salt thereof.15. The pharmaceutical composition of claim 14 , further comprising a second therapeutic agent selected from the group consisting of HCV antiviral agents claim 14 , immunomodulators claim 14 , and anti-infective agents.16. The pharmaceutical composition of claim 15 , wherein the second therapeutic agent is selected from the group consisting of HCV NS3 and NS3/4A protease inhibitors claim 15 , HCV NS5A inhibitors and HCV NS5B polymerase inhibitors.1718-. (canceled)19. A method of treating a patient infected with HCV claim 1 , the method comprising administering to the patient the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , in an amount effective to prevent and/or treat infection by HCV in the patient.20. The method of claim 19 , further comprising ...

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. I

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. I

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. I

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Inhibitors of diacylglycerol acyltransferase

The present invention relates to novel heterocyclic compounds as diacylglycerol acyltransferase ("DGAT") inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the invention is shown below: formula (I).

Heterocyclic compounds and methods of use thereof for the treatment of hepatitis c

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.(I)

Dimeric compounds

The present invention provides a compound of formula I which act as inhibitors of SMAC protein binding to Inhibitor of Apoptosis Proteins (IAPs), and/or inhibitors of activated caspase protein binding to IAPs (I) their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances, alone or in combination with DR5/FAP agonist antibodies. The active compound of the present invention is useful in the amelioration, treatment or control of cancer, especially solid tumors.

BENZODIAZEPINE DERIVATIVES LIKE GABA A GAMMA1 PAMS

DERIVADOS DE BENZODIAZEPINA COMO GABA A GAMMA1 PAMS. A presente invenção refere-se a compostos tendo a fórmula geral (I) em que R1, R2, R3, R4, R5 e X são como descritos no presente documento, composições incluindo os compostos e métodos de uso dos compostos. BENZODIAZEPINE DERIVATIVES SUCH AS GABA A GAMMA1 PAMS. The present invention relates to compounds having the general formula (I) wherein R1, R2, R3, R4, R5 and X are as described herein, compositions including the compounds and methods of using the compounds.

Pyridazinone derivatives useful as glucan synthase inhibitors

Benzodiazepine derivatives as gaba a gamma1 pams

La invención proporciona compuestos novedosos que tienen la fórmula general (I) en donde R¹, R², R³, R⁴, R⁵y X son como se describe en la presente, en donde las composiciones incluyen los compuestos y métodos de uso de los compuestos.

Pyridazinone derivatives useful as glucan synthase inhibitors

In its many embodiments, the present invention provides -substituted pyridazinone compounds as glucan synthase inhibitors, methods of preparing such compounds, pharmaceutical including one or more of such compounds, methods of preparing pharmaceutical formulations including one or more such compounds or one or more such compounds along with other antifungal agents, and methods of treatment, prevention, inhibition, or amelioration of one or more fungal infections associated with glucan synthase using such compounds or pharmaceutical compositions.

Heterobicyclo-substituted-[1,2,4]triazolo[1,5-c]quinazolin-5-amine compounds with a2a antagonist properties

Benzodiazepine derivatives as gaba a gamma1 pams

The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5 and X are as described herein, compositions including the compounds and methods of using the compounds.

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. I

Bicyclic compounds as inhibitors of diacylglycerol acyltransferase

The present invention relates to novel heterocyclic compounds as diacylglycerol acyltransferase (“DGAT”) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the invention is shown below: formula (I).

Dimeric compounds

The present invention provides a compound of formula I which act as inhibitors of SMAC protein binding to Inhibitor of Apoptosis Proteins (IAPs), and/or inhibitors of activated caspase protein binding to IAPs (I) their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances, alone or in combination with DR5/FAP agonist antibodies. The active compound of the present invention is useful in the amelioration, treatment or control of cancer, especially solid tumors.

COMPOUND AND PHARMACEUTICAL COMPOSITION

COMPOSTO, E, COMPOSIÇÃO FARMACÊUTICA. São descritos compostos da Fórmula G1 (estruturalmente representados): onde "RG3", "Rd1" a "Rd4", "n", "m", "p", "W", "X", "Y" e "Z" são aqui definidos, compostos estes que são antagonistas do receptor de A2A. Também são aqui descritos os usos dos compostos aqui descritos como antagonistas do receptor de A2a no tratamento ou prevenção potenciais de distúrbios e doenças neurológicas em que os receptores de A2A estão envolvidos. Também são aqui descritas composições farmacêuticas compreendendo estes compostos e usos destas composições farmacêuticas. COMPOUND AND PHARMACEUTICAL COMPOSITION. Compounds of Formula G1 are described (structurally shown): where "RG3", "Rd1" to "Rd4", "n", "m", "p", "W", "X", "Y" and "Z " are defined herein, which compounds are A2A receptor antagonists. Also described herein are the uses of the compounds described herein as A2a receptor antagonists in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions are also described herein.

Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. (I)

Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis C

The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Benzodiazepine derivatives as gaba a gamma1 pam

Compounds having the general formula (I)wherein R1, R2, R3, R4, R5 and X are as described herein, compositions including the compounds and methods of using the compounds.

Benzodiazepine derivatives as gaba a gamma1 pams

The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 and X are as described herein, compositions including the compounds and methods of using the compounds.

Derivados de benzodiazepinas como moduladores alostericos positivos (pam) de acido gamma-aminobutirico (gaba) a gamma1.

La invención proporciona compuestos novedosos que tienen la fórmula general (I) (ver Fórmula) (I) en donde R1, R2, R3, R4, R5 y X son como se describe en la presente, en donde las composiciones incluyen los compuestos y métodos de uso de los compuestos.

SUBSTITUTED BENZO[f][l ,2,4JTRIAZOL0[4,3-a][l ,4JDIAZEPINES AS GABA A GAMMA! POSITIVE ALLOSTERIC MODULATORS

Compounds having the general formula (I)wherein R1, R2, R3, R4, R5 and X are as described herein, compositions including the compounds and methods of using the compounds.

Benzodiazepine derivatives as gaba a gamma1 pam

The invention provides novel compounds having the general formula (I) wherein R1, R3, R4, R5 and X are as described herein, compositions including the compounds and methods of using the compounds.

Benzodiazepine derivatives as gaba a gamma1 pam

Benzodiazepine derivatives as gaba a gamma1 pam

DERIVADOS DE BENZODIAZEPINA COMO PAM DE GABAA g1

Compuestos derivados de 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepina como moduladores alostéricos positivos (PAM) de GABAA g1, un proceso para su preparación, una composición farmacéutica que comprende a uno de éstos compuestos y el uso de los mismos para el tratamiento o profilaxis del trastorno del espectro autista, el síndrome de Rett, trastornos de estrés postraumático y el síndrome del cromosoma X frágil. Reivindicación 1: Un compuesto de la fórmula (1) en donde R¹ se selecciona de i) H, ii) C₁₋₆-alquilo, iii) C₁₋₆-alcoxi, iv) C₁₋₆-alcoxi-C₁₋₆-alquilo, v) hidroxi, vi) hidroxi-C₁₋₆-alquilo, vii) C₃₋₈-cicloalquilo opcionalmente sustituido con R⁷, R⁸ y R⁹, viii) amino-C₁₋₆-alquilo, ix) heteroarilo opcionalmente sustituido con R⁷, R⁸ y R⁹, y x) heterocicloalquilo opcionalmente sustituido con R⁷, R⁸ y R⁹; R³ se selecciona de i) Cl, y ii) F; X se selecciona de i) CR⁶, y ii) N; R⁶ se selecciona de i) H, ii) Cl, y iii) F; R⁴ se selecciona de i) Br, y ii) Cl; R⁵ se selecciona de i) C₁₋₆-alquilo, ii) C₁₋₆-alcoxi, iii) halógeno, iv) halo-C₁₋₆-alquilo, v) ciano, y vi) C₃₋₈-cicloalquilo; R⁷, R⁸ y R⁹ se seleccionan independientemente de i) C₁₋₆-alquilo, y ii) C₁₋₆-alcoxi; o sales aceptables desde el punto de vista farmacéutico.

Benzodiazepine derivatives as gaba a gamma1 pam

The invention provides novel compounds having the general formula (I) wherein R 1 , R 3 , R 4 , R 5 and X are as described herein, compositions including the compounds and methods of using the compounds.

Benzodiazepine derivatives as gaba a gamma1 pams

New cyclopenta-thieno-diazepine derivatives as gaba a gamma1 pam

The invention provides novel heterocyclic compounds having the general formula (I), and pharmaceutically acceptable salts thereof, wherein the variables are as described herein (formula (I)). Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, inparticular methods of using the compounds for the treatment or prevention of acute neurological disorders, chronic neurological disorders and/or cognitive disorders.

New cyclopenta-thieno-diazepine derivatives as gaba a gamma1 positive allosteric modulators

The invention provides heterocyclic compounds having the general formula (1), and pharmaceutically acceptable salts thereof, wherein the variables are as described herein.Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds for the treatment or prevention of acute neurological disorders, chronic neurological disorders and/or cognitive disorders. release wednesday

Derivados de benzodiazepinas como pam de gaba a gamma1

Referido a un compuesto de formula I, en donde R1 se selecciona de H, alquil C1-6, alcoxi C1-6, entre otros; R2 se selecciona de alquil C1-6, hidroxi, hidroxi-alquil C1-6 y alcoxi C1-6-alquil C1-6; R3 se selecciona de Cl y F; X se selecciona de CR6 y N; R4 se selecciona de Br y Cl; R5 se selecciona de alquil C1-6, alcoxi C1-6, halogeno, halo-alquil C1-6, entre otros. Un compuesto seleccionado es (4S)-8-bromo-7-cloro-6-(2-fluorofenil)-4-metil-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepina. Estos compuestos derivados de benzodiazepinas son moduladores alostericos positivos (PAM) de GABA A gamma1. Tambien se refiere a procesos para la preparacion de dicho compuesto y su uso en el trastorno o profilaxis de enfermedades relacionadas con el receptor GABA A gamma1, tales como trastorno del espectro autista (ASD) dirigidos a los sintomas centrales y comorbilidades asociadas que incluye ansiedad e irritabilidad, sindrome de Angelman, entre otros.

Substituted benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepines as GABA A GAMMA1 positive allosteric modulators

Compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 and X are as described herein, compositions including the compounds and methods of using the compounds.