- Discovery of a new series of potent prostacyclin receptor agonists with in vivo activity in rat
-
The design and synthesis of two closely related series of prostacyclin receptor agonist compounds that showed excellent human IP receptor potency and efficacy is described. Compounds from this series showed in vivo activity after SC dosing in the monocrotaline model of PAH in rat.
- Tran, Thuy-Anh,Shin, Young-Jun,Kramer, Bryan,Choi, Juyi,Zou, Ning,Vallar, Pureza,Martens, Peter,Douglas Boatman,Adams, John W.,Ramirez, Juan,Shi, Yunqing,Morgan, Michael,Unett, David J.,Chang, Steve,Shu, Hsin-Hui,Tung, Shiu-Feng,Semple, Graeme
-
p. 1030 - 1035
(2015/02/19)
-
- Azabicyclic heterocycles as cannabinoid receptor modulators
-
The present application describes compounds according to Formula I, pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents and methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents. The compounds have the general Formula I and Formula II: including all prodrugs, pharmaceutically acceptable salts and stereoisomers, R1, R2, R3 and R4 are described herein.
- -
-
Page/Page column 12
(2008/06/13)
-
- Macrocyclic hepatitis C serine protease inhibitors
-
The present invention relates to compounds of Formula I, II or Ill, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: wherein W is a substituted or unsubstituted heterocyclic ring system. The compounds inhibit serine protease activity, particularly the activity of hepatitis c virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis c virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
- -
-
Page/Page column 165-166
(2008/06/13)
-
- Azabicyclic heterocycles as cannabinoid receptor modulators
-
The present application describes compounds according to Formula I, pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents and methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents. The compounds have the general Formula I: including all prodrugs, pharmaceutically acceptable salts and stereoisomers, R1, R2, R3, R6, R7, m and n are described herein.
- -
-
Page/Page column 79
(2008/06/13)
-
- Synthesis of 4-aryl-5-hydroxy- and 5-aryl-4-hydroxypyridazin-3(2H)-ones and their use in the preparation of 4,5-diarylpyridazin-3(2H)-ones and hitherto unknown isochromeno[3,4-d]pyridazinediones
-
Easily accessible 2-substituted 4-aryl-5-methoxy- and 2-substituted 5-aryl-4-methoxypyridazin-3(2H)-ones were transformed into the corresponding aryl-hydroxypyridazin-3(2H)-ones by alkaline hydrolysis. The use of these compounds in the synthesis of 2-substituted 4,5-diarylpyridazin-3(2H)-ones with two differently substituted aryl groups was investigated. Two aryl-hydroxypyridazin-3(2H)-ones, 2-(2-benzyl-5-hydroxy-3-oxo-2,3-dihydropyridazin-4-yl)benzaldehyde and 2-(1-benzyl-5-hydroxy-6-oxo-1,6-dihydropyridazin-4-yl)benzaldehyde, were transformed into 2-benzyl-1H-isochromeno[3,4-d]pyridazine-1,6(2H)-dione and 3-benzyl-3H-isochromeno[3,4-d]pyridazine-4,6-dione, respectively, via oxidation of the formyl group with KMnO4 followed by lactonization.
- Maes, Bert U.W,Monsieurs, Katrien,Loones, Kristof T.J,Lemière, Guy L.F,Dommisse, Roger,Mátyus, Péter,Riedl, Zsuzsanna,Hajós, Gy?rgy
-
p. 9713 - 9721
(2007/10/03)
-
- Synthesis of new pyridazino[4,5-c]isoquinolinones by Suzuki cross-coupling reaction
-
Suzuki cross-coupling reaction of 2-alkyl(methyl and benzyl)-5-chloro-4-methoxy- and 2-alkyl(methyl and benzyl)-4-chloro-5-methoxypyridazin-3(2H)-ones with 2-formylphenylboronic acid afforded the corresponding biaryl products which were cyclized with ammonia to yield hitherto undescribed pyridazino[4,5-c]isoquinolinones. Removal of the N-benzyl protective group in position 2 yielded the unsubstituted tricyclic pyridazinones.
- Riedl, Zsuzsanna,Maes, Bert U.W,Monsieurs, Katrien,Lemière, Guy L.F,Mátyus, Péter,Hajós, Gy?rgy
-
p. 5645 - 5650
(2007/10/03)
-