Design and synthesis of 1-(1-benzothiophen-7-yl)-1H-pyrazole, a novel series of G protein-coupled receptor 52 (GPR52) agonists

Nakahata, Takashi; Tokumaru, Kazuyuki; Ito, Yoshikatsu; Ishii, Naoki; Setoh, Masaki; Shimizu, Yūji; Harasawa, Toshiya; Aoyama, Kazunobu; Hamada, Takashi; Kori, Masakuni; Aso, Kazuyoshi

doi:10.1016/j.bmc.2018.02.005

Cited by 21 publications

(22 citation statements)

References 16 publications

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“…Surprisingly, two G protein-coupled receptors were found among the upregulated genes by RNA-seq analysis: GPR52 and GPR35 (Supplementary Table 2 ). GPR52 is a Gs protein-coupled receptor 39 , 40 , whereas GPR35 is a Gi/o protein-coupled receptor 41 , 42 . Therefore, we speculated that GPR35 was involved in DP7 signaling.…”

Section: Resultsmentioning

confidence: 99%

Rational design of innate defense regulator peptides as tumor vaccine adjuvants

Tian

Zhang

et al. 2021

npj Vaccines

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The development of adjuvants has been an empirical process. Efforts to develop a new design and evaluation system for novel adjuvants are not only desirable but also necessary. Moreover, composite adjuvants that contain two or more types of adjuvants to synergistically enhance the immune response are important for adjuvant and vaccine design. Innate defense regulator peptides (IDRs) are promising adjuvants for clinical immunotherapy because they exhibit multifaceted immunomodulatory capabilities. However, the rational design and discovery of IDRs that have improved immunomodulatory activities have been hampered by the lack of screening techniques and the great challenges in the identification of their interaction partners. Here, we describe a screening and evaluation system for IDR design. On the basis of in vitro screening, the optimized IDR DP7 recruited neutrophils, monocytes and macrophages to the site of infection. The adjuvant, comprising the DP7 and CpG oligonucleotide (CpG), induced chemokine/cytokine expression, enhanced the antigen uptake by dendritic cells and upregulated surface marker expression in dendritic cells. Vaccination with the NY-ESO-1 or OVA antigens combined with the adjuvant alum/CpG/DP7 strongly suppressed tumor growth in mice which was due to the improvement of antigen-specific humoral and cellular immunity. Regarding the mechanism of action, GPR35 may be the potential interaction partner of DP7. Our study revealed the potential application of the screening and evaluation system as a strategy for rationally designing effective IDRs or composite adjuvants and identifying their mechanism of action.

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Section: Resultsmentioning

confidence: 99%

Rational design of innate defense regulator peptides as tumor vaccine adjuvants

Tian

Zhang

et al. 2021

npj Vaccines

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“…The synthesis of designed analogue is shown in Scheme-I. Chalcone analogues (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) were synthesized from dehydroacetic acid (1) and substituted benzaldehydes (2) via condensation reaction as earlier reported procedure.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of New Dihydropyrazoles of Designed Curcumin Analogues

Tripathi

2019

Asian J. Chem.

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Present work demonstrates a facile synthesis of a series of 20 dihydropyrazole derivatives from well designed curcumin analogues by reaction of chalcone derivatives with phenylhydrazine. All the synthesized compounds were characterized by spectroscopic (1H and 13C NMR, IR spectra), spectrometric (Mass spectra) data and elemental analysis. Synthesized dihydropyrazoles have diversity points on attached phenyl ring. Effect of substituent on reactivity was explained on the basis of electronic effect generated due to groups on phenyl ring. Presence of dd (double doublet) in 1H NMR spectrum of dihydropyrazoles was also explained due to presence of optically active carbon of pyrazole ring.

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“…Because of this segregated expression pattern, it was hypothesized that the GPR52 activation of Gαs could stimulate cAMP production, counteracting the effect of Gαi-activation by dopamine D2 receptors [ 81 ]. Such a hypothesis led to the development of many synthetic ligands to be potentially used in the treatment of schizophrenia [ 181 , 182 , 183 ].…”

Section: Systematic Analysis Of Ogpcrs In Anxiety and Mood Disordementioning

confidence: 99%

Orphan G Protein Coupled Receptors in Affective Disorders

Watkins

Orlandi

2020

Genes

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G protein coupled receptors (GPCRs) are the main mediators of signal transduction in the central nervous system. Therefore, it is not surprising that many GPCRs have long been investigated for their role in the development of anxiety and mood disorders, as well as in the mechanism of action of antidepressant therapies. Importantly, the endogenous ligands for a large group of GPCRs have not yet been identified and are therefore known as orphan GPCRs (oGPCRs). Nonetheless, growing evidence from animal studies, together with genome wide association studies (GWAS) and post-mortem transcriptomic analysis in patients, pointed at many oGPCRs as potential pharmacological targets. Among these discoveries, we summarize in this review how emotional behaviors are modulated by the following oGPCRs: ADGRB2 (BAI2), ADGRG1 (GPR56), GPR3, GPR26, GPR37, GPR50, GPR52, GPR61, GPR62, GPR88, GPR135, GPR158, and GPRC5B.

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Design and synthesis of 1-(1-benzothiophen-7-yl)-1H-pyrazole, a novel series of G protein-coupled receptor 52 (GPR52) agonists

Cited by 21 publications

References 16 publications

Rational design of innate defense regulator peptides as tumor vaccine adjuvants

Rational design of innate defense regulator peptides as tumor vaccine adjuvants

Synthesis of New Dihydropyrazoles of Designed Curcumin Analogues

Orphan G Protein Coupled Receptors in Affective Disorders

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