- Discovery and synthesis of 6,7,8,9-tetrahydro-5H-pyrido[4,3-c]azepin-5-one-based novel chemotype CCR2 antagonists via scaffold hopping strategy
-
The chemokine CC receptor subtype 2 (CCR2) has attracted intensive interest for drug development in diverse therapeutic areas, including chronic inflammatory diseases, diabetes, neuropathic pain, atherogenesis and cancer. By employing a cut-and-sew scaffold hopping strategy, we identified an active scaffold of 3,4-dihydro-2,6-naphthyridin-1(2H)-one as the central pharmacophore to derive novel CCR2 antagonists. Systematic structure–activity relationship study with respect to the ring size and the substitution on the naphthyridinone ring gave birth to 1-arylamino-6-alkylheterocycle-6,7,8,9-tetrahydro-5H-pyrido[4,3-c]azepin-5-ones as a brand new chemotype of CCR2 antagonists with nanomolar inhibitory activity. The best antagonism activity in this series was exemplified by compound 13a, which combined the optimal substitutions of 3,4-dichlorophenylamino at C-1 and 3-(4-(N-methylmethylsulfonamido)piperidin-1-yl)propyl at N-6 position, leading to an IC50 value of 61 nM and 10-fold selectivity for CCR2 over CCR5. Efficient and general synthesis was established to construct the innovative core structure and derive the compound collections. This is the first report on our designed 6,7,8,9-tetrahydro-5H-pyrido[4,3-c]azepin-5-one as novel CCR2 antagonist scaffold and its synthesis.
- Qin, Li-Huai,Wang, Zhi-Long,Xie, Xin,Long, Ya-Qiu
-
p. 3559 - 3572
(2018/05/28)
-
- COMPOUNDS USEFUL AS FAAH MODULATORS AND USES THEREOF
-
Compounds are disclosed that have formula (I): where A, B, L1, X, W, Y, R1, R3, and nlare as defined herein. The compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, anxiety, depression, inflammation, cognitive disorders, weight and eating disorders, Parkinson's disease, Alzheimer's disease, spasticity, addiction, glaucoma, and others.
- -
-
Page/Page column 57
(2009/03/07)
-
- DIKETOPIPERIDINE DERIVATIVES AS HIV ATTACHMENT INHIBITORS
-
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, diketopiperidine derivatives that possess unique antiviral activity are provided. These compounds are useful for the treatment of HIV and AIDS.
- -
-
Page/Page column 83-84
(2010/01/30)
-
- 4-Piperidinecarboxamide modulators of vanilloid VR1 receptor
-
This invention is directed to vanilloid receptor VR1 ligands. More particularly, this invention relates to hetero isonipecotic amides that are potent modulators of VR1 which are useful for the treatment and prevention of disease conditions in mammals.
- -
-
Page/Page column 55
(2010/11/08)
-
- Condensed Heteroaromatic Ring Systems. III. Synthesis of Naphthyridine Derivatives by Cyclization of Ethynylpyridinecarboxamides
-
Four kinds of naphthyridinones, i.e. 1,6-naphthyridin-5-one, 1,7-naphthyridin-8-one, 2,6-naphthyridin-2-one, and 2,7-naphthyridin-1-one derivatives, were commonly synthesized by the intramolecular cyclization of pyridinecarboxamides having an ethynyl group or β,β-dimethoxyethyl group adjacent to the carbamoyl group.The syntheses of the starting pyridine derivatives were easily accomplished by cross-coupling of the corresponding halopyridines with acetylenes.Keywords-intramolecular cyclization; palladium catalyst; trimethylsilylacetylene; naphthyridinone; pyridineacetaldehyde; 1(2H)-isoquinolone
- Sakamoto, Takao,Kondo, Yoshinori,Yamanaka, Hiroshi
-
p. 626 - 633
(2007/10/02)
-
- Amination of 2,6- and 2,7-Naphtyridine. An NMR Study on ?-Adducts of Heterocyclic Systems with Amide Ions
-
A facile synthesis of 2,6-naphtyridine is described.Both 2,6- and 2,7-naphtyridine undergo with potassium amide under kinetically and thermodynamically controlled conditions ?-adduct formation at position 1.Chichibabin amination of 2,6-naphtyridine yields 1-amino-2,6-naphtyridine in 54percent yield.
- Haak, Henk J. W. van den,Plas, Henk C. van der,Veldhuizen, Beb van
-
p. 1349 - 1352
(2007/10/02)
-