- OXADIAZOLE TRANSIENT RECEPTOR POTENTIAL CHANNEL INHIBITORS
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The invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof wherein A, X, R1, R4 and n are as defined herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
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- INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND/OR TRYPTOPHAN 2,3-DIOXYGENASE
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The present invention relates to compounds of Formula (I) inhibiting indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO) enzymes. Further, their synthesis and their use as medicaments in inter alia cancer is disclosed.
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Page/Page column 66; 72
(2019/03/05)
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- INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND/OR TRYPTOPHAN 2,3-DIOXYGENASE
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The present invention relates to compounds of Formula (I) inhibiting indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO) enzymes. Further, their synthesis and their use as medicaments in inter alia the treatment of cancer is disclosed. Formula (I)
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Page/Page column 76; 79
(2019/08/20)
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- OXADIAZOLONES AS TRANSIENT RECEPTOR POTENTIAL CHANNEL INHIBITORS
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The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
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- OXAZOLE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the oxazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
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- OXAZOLE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the oxazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 48
(2015/02/25)
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- Synthesis and structure-activity relationships of novel zwitterionic compounds as peroxisome proliferator activated receptor α/γ dual agonists with improved physicochemical properties
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We describe herein the design, syntheses and structure-activity relationships (SAR) of novel zwitter-ionic compounds as non-thiazolidinedion (TZD) based peroxisome proliferator activated receptor (PPAR) α/γ dual agonists. In the previous report, we obtained compound 1 showing potent PPARα/γ dual agonistic activities, together with a great glucose lowering effect in the db/db mice. However, this compound possessed fatal issues such as potent cytochrome P450 (CYP)3A4 direct inhibitory activity. Thus, we carried out the medicinal optimization to improve these while maintaining the potent PPAR agonistic activity. As a result, the issues were addressed by changing the furan ring to a low lipophilic 1,3,4-oxadiazole ring. Additionally, these oxadiazole derivatives exhibited a significant decrease in plasma glucose and plasma triglyceride levels without marked weight gain.
- Shibata, Yoshihiro,Kagechika, Katsuji,Yamaguchi, Mitsuhiro,Yoshikawa, Kenji,Chiba, Kiyoshi,Takano, Hiromichi,Akiyama, Chiyuki,Ono, Mayumi,Nishi, Mina,Kubo, Hideo,Kobayashi, Yoshimasa,Usui, Hiroyuki
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p. 1248 - 1263
(2014/01/06)
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- 3-AZA-BICYCLO[3.1.0]HEXANE DERIVATIVES
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The invention relates to 3-aza-bicyclo[3.1.0]hexane derivatives of formula (I) wherein A, B, n, X, and R1 are as described in the description, and salts thereof, and their use as orexin receptor antagonists.
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Page/Page column 41
(2010/02/17)
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- TRANS-3-AZA-BICYCLO[3.1.0]HEXANE DERIVATIVES
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The invention relates to novel trans-3-aza-bicyclo[3.1.0]hexane derivatives of formula (I), wherein A, B, n and R1 are as described in the description, and to the use of such compounds, or of pharmaceutically acceptable salts of such compounds, as medicaments, especially as orexin receptor antagonists.
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Page/Page column 77
(2009/03/07)
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- 2-AZA-BICYCLO[3.1.0]HEXANE DERIVATIVES
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The invention relates to novel 2-aza-bicyclo[3.1.0]hexane derivatives of Formula (I) wherein A, B, n and R1 are as described in the description, and to the use of such compounds, or of pharmaceutically acceptable salts of such compounds, as medicaments, especially as orexin receptor antagonists.
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Page/Page column 66-67
(2008/12/07)
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- Bromobenzofuran-based non-peptide antagonists of angiotensin II: GR138950, a potent antihypertensive agent with high oral bioavailability
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We have identified GR138950, a potent antagonist of the angiotensin II receptor with high oral bioavailability, as our second drug candidate to GR117289. Using GR117289, a compound with moderate bioavailability (20%) in man as a lead, we pursued a strategy aimed at enhancing bioavailability. The strategy was based on SAR established around the diacid GR117289, and from this, it was proposed that a monoacid, in particular a trifluoromethanesulfonamide, should be better absorbed after oral administration and have enhanced oral bioavailability. This led to the identification of GR138950, a potent antihypertensive agent in the renal hypertensive rat, causing sustained falls in blood pressure after oral administration. Oral bioavailability of GR138950 in rats and dogs is high, confirming that GR138950 is well absorbed after oral administration. Moreover, the low plasma clearance and long plasma half-life suggest that this compound will be suitable for once a day administration. Furthermore, the preliminary data indicate that the high bioavailability of GR138950 seen in rats and dogs translates to man. These results demonstrate clearly that GR138950 has the potential to be a clinically effective antihypertensive agent. Further studies are in progress to evaluate GR138950 in the treatment of hypertension.
- Judd,Dowle,Middlemiss,Scopes,Ross,Jack,Pass,Tranquillini,Hobson,Panchal,Stuart,Paton,Hubbard,Hilditch,Drew,Robertson,Clark,Travers,Hunt,et al.
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p. 3108 - 3120
(2007/10/02)
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- An Enantioselective Synthesis of L-Threonine
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An enantioselective synthesis of L-threonine (1) is described.Racemic ethyl 2-acetamido-3-oxobutyrate (6) was synthesized from ethyl acetoacetate (2) (4) (5) and then transformed to the epimeric optically active alcohols 7a and 7b by microbiological reduction with Saccharomyces rouxii.The mixture 7a/7b could be converted to 1 by slightly modified, known methods in a yield of ca. 52percent with respect to 7a/7b.
- Soukup, Milan,Wipf, Beat,Hochuli, Erich,Leuenberger, Hans G. W.
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p. 232 - 236
(2007/10/02)
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