Patent classifications
C07D207/50
2-PHENYL-3,4-DIHYDROPYRROLO[2,1 -F] [1,2,4]TRIAZINONE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS AND USES THEREOF
The present invention relates to compounds of formula I
##STR00001##
or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein R.sub.1 is C.sub.1-C.sub.3alkyl optionally substituted with F, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3alkoxy; X represents a bond or C.sub.1-C.sub.3alkylene optionally substituted with OH, ONO, ONO.sub.2; R.sub.2 is H, OH, ONO, ONO.sub.2, C(O)OH, C(O)OC.sub.1-C.sub.3alkyl, CHO, CN, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl, CR.sub.8NOR.sub.9, CR.sub.8NNR.sub.10R.sub.11, CR.sub.8NR.sub.12 or CR.sub.8NONO.sub.2; R.sub.3 is C.sub.1-C.sub.6alkyl optionally substituted with F, OH, ONO, ONO.sub.2, C.sub.1-C.sub.3alkoxy, C.sub.3-C.sub.6cycloalkyl; C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl; R.sub.4 is C.sub.1-C.sub.6alkyl optionally substituted with C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6alkoxy, F, ONO, ONO.sub.2; C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl; R.sub.5 is H, SO.sub.2NR.sub.13R.sub.14, NHSO.sub.2NR.sub.13R.sub.14; R.sub.6 is H or C.sub.1-C.sub.3alkyl; R.sub.7 is H, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3alkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C.sub.1-C.sub.3alkyl, F; R.sub.8 is H, CH.sub.3 or C.sub.2H.sub.5; R.sub.9: H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl; R.sub.10 and R.sub.11 are each independently H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C.sub.1-C.sub.3 alkyl; R.sub.12 is C.sub.1-C
Methods of preparing tecovirimat
Disclosed are methods for the preparation of Tecovirimat for the treatment or prophylaxis of viral infections and diseases associated therewith, particularly those viral infections and associated diseases caused by the orthopoxvirus.
Methods of preparing tecovirimat
Disclosed are methods for the preparation of Tecovirimat for the treatment or prophylaxis of viral infections and diseases associated therewith, particularly those viral infections and associated diseases caused by the orthopoxvirus.
MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE
Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases such as chronic viral infection, chronic bacterial infections, cancer, sepsis or a neurological disorder.
##STR00001##
MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE
Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases such as chronic viral infection, chronic bacterial infections, cancer, sepsis or a neurological disorder.
##STR00001##
2-phenyl-3,4-dihydropyrrolo[2,1 -F] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof
The present invention relates to compounds of formula I ##STR00001##
or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein
R.sub.1 is C.sub.1-C.sub.3alkyl optionally substituted with F, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3alkoxy;
X represents a bond or C.sub.1-C.sub.3alkylene optionally substituted with OH, ONO, ONO.sub.2;
R.sub.2 is H, OH, ONO, ONO.sub.2, C(O)OH, C(O)OC.sub.1-C.sub.3alkyl, CHO, CN, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl, CR.sub.8NOR.sub.9, CR.sub.8NNR.sub.10R.sub.11, CR.sub.8NR.sub.12 or CR.sub.8NONO.sub.2;
R.sub.3 is C.sub.1-C.sub.6alkyl optionally substituted with F, OH, ONO, ONO.sub.2, C.sub.1-C.sub.3alkoxy, C.sub.3-C.sub.6cycloalkyl; C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl;
R.sub.4 is C.sub.1-C.sub.6alkyl optionally substituted with C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6alkoxy, F, ONO, ONO.sub.2; C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl;
R.sub.5 is H, SO.sub.2NR.sub.13R.sub.14, NHSO.sub.2NR.sub.13R.sub.14;
R.sub.6 is H or C.sub.1-C.sub.3alkyl;
R.sub.7 is H, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3alkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C.sub.1-C.sub.3alkyl, F;
R.sub.8 is H, CH.sub.3 or C.sub.2H.sub.5;
R.sub.9: H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl;
R.sub.10 and R.sub.11 are each independently H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C.sub.
2-phenyl-3,4-dihydropyrrolo[2,1 -F] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof
The present invention relates to compounds of formula I ##STR00001##
or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein
R.sub.1 is C.sub.1-C.sub.3alkyl optionally substituted with F, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3alkoxy;
X represents a bond or C.sub.1-C.sub.3alkylene optionally substituted with OH, ONO, ONO.sub.2;
R.sub.2 is H, OH, ONO, ONO.sub.2, C(O)OH, C(O)OC.sub.1-C.sub.3alkyl, CHO, CN, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl, CR.sub.8NOR.sub.9, CR.sub.8NNR.sub.10R.sub.11, CR.sub.8NR.sub.12 or CR.sub.8NONO.sub.2;
R.sub.3 is C.sub.1-C.sub.6alkyl optionally substituted with F, OH, ONO, ONO.sub.2, C.sub.1-C.sub.3alkoxy, C.sub.3-C.sub.6cycloalkyl; C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl;
R.sub.4 is C.sub.1-C.sub.6alkyl optionally substituted with C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6alkoxy, F, ONO, ONO.sub.2; C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl;
R.sub.5 is H, SO.sub.2NR.sub.13R.sub.14, NHSO.sub.2NR.sub.13R.sub.14;
R.sub.6 is H or C.sub.1-C.sub.3alkyl;
R.sub.7 is H, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3alkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C.sub.1-C.sub.3alkyl, F;
R.sub.8 is H, CH.sub.3 or C.sub.2H.sub.5;
R.sub.9: H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl;
R.sub.10 and R.sub.11 are each independently H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C.sub.
COMPOUNDS CONTAINING S-N-VALERYL-N-{[2'-(1H-TETRAZOLE-5-YL)-BIPHENYL-4-YL]-METHYL}-VALINE AND (2R,4S)-5-BIPHENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-PENTANOIC ACID ETHYL ESTER MOIETIES AND CATIONS
A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na.sup.+ useful for the treatment of hypertension and/or heart failure.
COMPOUNDS CONTAINING S-N-VALERYL-N-{[2'-(1H-TETRAZOLE-5-YL)-BIPHENYL-4-YL]-METHYL}-VALINE AND (2R,4S)-5-BIPHENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-PENTANOIC ACID ETHYL ESTER MOIETIES AND CATIONS
A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na.sup.+ useful for the treatment of hypertension and/or heart failure.
COMPOUNDS CONTAINING S-N-VALERYL-N-{[2'-(1H-TETRAZOLE-5-YL)-BIPHENYL-4-YL]-METHYL}-VALINE AND (2R,4S)-5-BIPHENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-PENTANOIC ACID ETHYL ESTER MOIETIES AND CATIONS
A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na+ useful for the treatment of hypertension and/or heart failure.