Discovery of FK453, a novel non-xanthine adenosine A1 receptor antagonist

Akahane, Atsushi; Katayama, Hirohito; Mitsunaga, Takafumi; Kita, Yasuhiro; Kusunoki, Takahiro; Terai, Takao; Yoshida, Keizo; Shiokawa, Youichi

doi:10.1016/0960-894x(96)00368-x

Cited by 27 publications

(18 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A seven-step synthesis of C,N,N-cyclic azomethine imines, 7substituted 2-oxo-Δ 7 -hexahydropyrazolo [1,5-a]pyridin-8-ium-1-ides 12, from δ-acyl butyric acids 14 was developed as an alternative to the previously described three-step process starting with acid chlorides 7 and pent-4-en-1-ylmagnesium bromide (8). 18 Though requiring a longer synthesis time, the present method allows large-scale preparation of cyclic dipoles 12, while the shorter and more elegant three-step synthesis 18 has a scale limitation (<0.5 mmol).…”

Section: Discussionmentioning

confidence: 99%

“…In this context, pyrazolo[1,5- a ]pyridine ( 1 ) belongs to a group of well-explored systems with over 100000 hits and over 2500 references according to a SciFinder substructure search. Derivatives of 1 exhibit different biological activities, such as antiviral activity, inhibition of reverse transcriptase, dopamine D3 and D4 antagonist, dopamine D3 agonist, diuretic adenosine A1 antagonist, and intercalating activity . A phosphodiesterase inhibitor, ibudilast ( 2 ), is an approved anti-inflammatory drug .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a¹-diazacyclopenta[cd]inden-2-ones

et al. 2016

View full text Add to dashboard Cite

Two cyclic azomethine imines, 7-methyl- and 7-phenyl-2-oxo-Δ-hexahydropyrazolo[1,5-a]pyridin-8-ium-1-ide, were prepared in seven steps from the respective commercially available δ-keto acids. The addition of Grignard reagents followed by N-alkylation at position 1 afforded the 1,7,7-trisubstituted hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones, whereas 1,3-dipolar cycloadditions of these dipoles to typical acetylenic and olefinic dipolarophiles gave 4a-substituted 2a,2a-diazacyclopenta[cd]indene derivatives as the first representatives of a novel heterocyclic system. Regio- and stereoselectivity as well as the mechanism of these [3 + 2]-cycloadditions were evaluated using computational and experimental methods. The data obtained were in agreement with the polar concerted cycloaddition mechanism via the energetically favorable syn/endo-transition states.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a¹-diazacyclopenta[cd]inden-2-ones

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Akahane and coworkers reported a series of pyrazolo-[1,5- a ]pyridine derivatives as potent and selective A 1 AR antagonists. FK453 ( 45 in Figure 9 ) [ 47 ] and FK838 ( 46 ) [ 48 ] were the typical examples of such derivatives, and they also showed diuretic activity both in vivo and in vitro . Nevertheless, there were some limitations in these two compounds.…”

Section: Pyrazolo Derivatives As Potent Ar Antagonistsmentioning

confidence: 99%

Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships

Cheong

Venkatesan

Paira

et al. 2011

International Journal of Medicinal Chemistry

View full text Add to dashboard Cite

In the past few decades, medicinal chemistry research towards potent and selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3) has been evolving rapidly. These antagonists are deemed therapeutically beneficial in several pathological conditions including neurological and renal disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of compounds have been successfully synthesized and identified as potent human adenosine receptor antagonists. In this paper, an overview of the structure-activity relationship (SAR) profiles of promising nonxanthine pyrazolo derivatives is reported and discussed. We have emphasized the SAR for some representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3-d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This overview not only clarifies the structural requirements deemed essential for affinity towards individual adenosine receptor subtypes, but it also sheds light on the rational design and optimization of existing structural templates to allow us to conceive new, more potent adenosine receptor antagonists.

show abstract

“…Subsequent condensation of the immediate cycloaddition product with hydrazine would then complete the formation of the dihydropyridazinone ring in just one additional step to form 8 (R 2 = H). We also considered that use of an alkynyl pyridazinone dipolarophile (9) might enable direct access to target compounds of type 10 in a single step. These routes might thus provide complementary access to both pyridazinone and dihydropyridazinone analogues whilst facilitating convenient multiple parallel synthesis of a wide range of pyridine ringsubstituted variants through combination of the dipolarophile with a set of substituted pyridine N-imines (11).…”

Section: Introductionmentioning

confidence: 99%

Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones

et al. 2008

View full text Add to dashboard Cite

Cycloaddition of pyridine N-imine with 6-alkyl-4-oxohex-5-ynoates followed by condensation with hydrazine provides concise access to pharmacologically active 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazinones. For the first time alkynyl heterocycles are also shown to be effective dipolarophiles for pyridine N-imine, and analogous compounds can be accessed directly in modest yields through the reaction of 6-(alkyn-1-yl)pyridazin-3-one derivatives.

show abstract

Discovery of FK453, a novel non-xanthine adenosine A1 receptor antagonist

Cited by 27 publications

References 15 publications

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a¹-diazacyclopenta[cd]inden-2-ones

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a¹-diazacyclopenta[cd]inden-2-ones

Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships

Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones

Contact Info

Product

Resources

About

Discovery of FK453, a novel non-xanthine adenosine A1 receptor antagonist

Cited by 27 publications

References 15 publications

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a1-diazacyclopenta[cd]inden-2-ones

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a1-diazacyclopenta[cd]inden-2-ones

Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships

Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones

Contact Info

Product

Resources

About

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a¹-diazacyclopenta[cd]inden-2-ones

Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a¹-diazacyclopenta[cd]inden-2-ones