- Synthesis and SAR Studies of 1 H-Pyrrolo[2,3- b]pyridine-2-carboxamides as Phosphodiesterase 4B (PDE4B) Inhibitors
-
Herein we report the synthesis, SAR, and biological evaluation of a series of 1H-pyrrolo[2,3-b]pyridine-2-carboxamide derivatives as selective and potent PDE4B inhibitors. Compound 11h is a PDE4B preferring inhibitor and exhibited acceptable in vitro ADME and significantly inhibited TNF-α release from macrophages exposed to pro-inflammatory stimuli (i.e., lipopolysaccharide and the synthetic bacterial lipopeptide Pam3Cys). In addition, 11h was selective against a panel of CNS receptors and represents an excellent lead for further optimization and preclinical testing in the setting of CNS diseases.
- Vadukoot, Anish K.,Sharma, Swagat,Aretz, Christopher D.,Kumar, Sushil,Gautam, Nagsen,Alnouti, Yazen,Aldrich, Amy L.,Heim, Cortney E.,Kielian, Tammy,Hopkins, Corey R.
-
supporting information
p. 1848 - 1854
(2020/11/09)
-
- THIENOPYRAZINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to thienopyrazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 28
(2016/09/26)
-
- THIENO (2, 3B) PYRAZINE COMPOUNDS AS B-RAF INHIBITORS
-
The invention relates to compounds according to general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of cancer.
- -
-
Paragraph 0110
(2013/04/10)
-
- Design, synthesis, and structure-activity relationships of novel spiro-piperidines as acetyl-CoA carboxylase inhibitors
-
Spiro-lactone (S)-1 is a potent acetyl-CoA carboxylase (ACC) inhibitor and was found to be metabolically liable in human hepatic microsomes. To remove one of the risk factors in human study by improving the metabolic stability, we focused on modifying the
- Kamata, Makoto,Yamashita, Tohru,Kina, Asato,Funata, Masaaki,Mizukami, Atsushi,Sasaki, Masako,Tani, Akiyoshi,Funami, Miyuki,Amano, Nobuyuki,Fukatsu, Kohji
-
scheme or table
p. 3643 - 3647
(2012/07/17)
-
- THIENO (2, 3B) PYRAZINE COMPOUNDS AS B - RAF INHIBITORS
-
The invention relates to compounds according to general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of cancer.
- -
-
Page/Page column 27
(2011/12/14)
-
- Application of the aza-Wittig reaction to the synthesis of pyrazinothienotriazolopyrimidinones: a new tetracyclic ring system
-
A simple one-pot and efficient method is described for the synthesis of pyrazinothienopyrimidines 6 by domino processes involving aza-Wittig/intermolecular nucleophilic addition/intramolecular cyclization. A tandem aza-Wittig reaction of phosphazenes 7, derived from 6, with heterocumulenes (isocyanates, carbon disulfide or carbon dioxide) generates the pyrazinothienotriazolopyrimidinones 9, 11 and 12, respectively. Pyrazino[2′,3′:4,5]thieno[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidin-4(3H)-ones 15 and bis(pyrazinothienotriazolopyrimidinones) 17 were synthesized by the intermolecular aza-Wittig reaction of phosphazenes 7 with acyl chlorides or α,ω-dichlorides followed by heterocyclization via imidoyl chloride intermediate 16. Further S-alkylation of 11 and reaction of 6 with phosgeniminium chloride produce 2-alkylthio- and 2-N,N-dimethylaminopyrazinothienotriazolopyrimidinones 13 and 19, respectively.
- Blanco, Gerardo,Quintela, José M.,Peinador, Carlos
-
p. 1333 - 1344
(2008/09/17)
-
- A practical one-pot procedure for the synthesis of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinones by a tandem aza-Wittig/heterocumulene-mediated annulation strategy
-
A simple one-pot and efficient method is described for the synthesis of pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidinone derivatives 6 via a tandem aza-Wittig/heterocumulene-mediated annulation process. The iminophosphorane 3 reacted with aryl isocyanates, fo
- Blanco, Gerardo,Seguí, Natalia,Quintela, José M.,Peinador, Carlos,Chas, Marcos,Toba, Rosa
-
p. 11124 - 11135
(2007/10/03)
-
- Benzopyranopyrrole and benzopyranopyridine alpha -1 adrenergic compounds
-
The present invention relates to a compound of the formula and the pharmaceutically acceptable salts thereof wherein W is a bicyclic heterocyclic ring system. The compounds are alpha -1 adrenergic antagonists and are useful in the treatment of BPH; also disclosed are alpha -1 antagonist compositions and a method for antagonizing alpha -1 adrenoreceptors and treating BPH.
- -
-
-
- 3-phenylpyrrolidine alpha-1 adrenergic compounds
-
Compounds having the formula are alpha 1 adrenoreceptor antagonists. Processes for making these compounds, synthetic intermediates employed in these processes and a method for inhibiting alpha 1 adrenoreceptors and treating benign prostatic hyperplasia (also called benign prostatic hypertrophy or BPH) and other urological diseases such as BOO (bladder outlet obstruction), neurogenic bladder and gynecological syndromes such as dysmenorrhea are disclosed.
- -
-
-
- Benzopyranopyrrole and benzopyranopyridine α-1 adenergic compounds
-
The present invention relates to a compound of the formula STR1 and the pharmaceutically acceptable salts thereof wherein W is a bicyclic heterocyclic ring system. The compounds are α-1 adrenergic antagonists and are useful in the treatment of BPH; also disclosed are α-1 antagonist compositions and a method for antagonizing α-1 adrenoreceptors and tr
- -
-
-