Adenosine A₁ receptor (A₁R) Antagonist

Derenofylline (SLV 320) is a potent, selective and orally active adenosine A₁ receptor antagonist, with K_i values of 1 nM, 200 nM and 398 nM for human A₁, A₃ and A_2A receptors respectively. Derenofylline suppresses cardiac fibrosis and attenuates albuminuria without affecting blood pressure in rats.

PSB36 is a highly selective A₁ adenosine receptor antagonist, with a K_i of 0.12 nM and a K_d of 0.7 nM. Systemic administration of PSB36 reduces formalin- and Carrageenan (HY-125474)-induced edema in mice and decreases pain-related behaviors, with no local paw activity. PSB36 prolongs the APD₉₀ of rat and human atria, produces a frequency-dependent prolongation of rat atrial ERP, increases the diastolic threshold of rat atria, and shortens the duration of atrial fibrillation episodes. PSB36 can be used in research related to inflammatory pain, inflammatory hyperalgesia, edema and atrial fibrillation.

FR194921 is a potent, selective and orally active and cross the blood-brain barrier Adenosine A1 antagonist with K_i value of 6.6, 5400 nM for A1, A2A, respectively. FR194921 shows cognitive-enhancing and anxiolytic activity.

KF20274 is an orally active adenosine A₁ receptor antagonist. KF20274 increases the fecal pellet output in rats, and does not affect small intestinal propulsion or gastric emptying at defecation-increasing doses. KF20274 does not induce diarrhea at defecation-increasing doses. KF20274 can be used for the research of constipation.

MRS1334 is a potent and selective human adenosine A₃ receptor antagonist with K_is of 2.69 nM, >100 nM, >100 nM for hA₃, rA₁, rA_2A, respectively. MRS1334 blocks the protective effect of Cl-IB-MECA leading to significant bradycardia and elevated ST segment. MRS1334 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

A1AR antagonist 6 (compound 15) is a potent and selective A1AR (A1 adenosine receptor) antagonist, with a pIC₅₀ of 6.38 and a pK_i of 7.13.

DMPX (3,7-Dimethyl-1-propargylxanthine) is a selective A_2A adenosine receptor (A_2A AR) antagonist that crosses the blood-brain barrier, with a K_i of 11 μM for rat A₂ adenosine receptor and a K_i of 45 μM for rat A₁ adenosine receptor. By blocking A2A receptors in specific brain regions, DMPX protects dopaminergic and GABAergic neurons from mitochondrial dysfunction. DMPX is applicable to research related to depression, Parkinson's disease and Huntington's disease.

A2A receptor antagonist 3 (Example 92) is an adenosine A2a receptor antagonist with a K_i of 0.4 nM. A2A receptor antagonist 3 also binds to A2b, A1 and A3 receptor with K_is of 37, 107 and 1467 nM, respectively.

A1AR antagonist 5 (compound 20) is a potent and selective A1AR (A1 adenosine receptor) antagonist, with a pIC₅₀ of 5.83 and a pK_i of 6.11.

A1AR antagonist 4 (compound 22) is a potent and selective A1AR (A1 adenosine receptor) antagonist, with a pIC₅₀ of 5.51 and a pK_i of 6.29.

LAS38096 is a potent, selective, and efficacious A2B Adenosine Receptor antagonist, with a K_i of 17 nM.

FK-352 is a selective adenosine A1 receptor antagonist. FK-352 significantly improves intradialytic hypotension in chronic hemodialysis. FK-352 can be used for the study of intradialytic hypotension.

Adenosine receptor antagonist 7 is an orally active triple A1/A2A/A2B adenosine receptor antagonist with K_i values of 1.5, 0.6 and 21 nM. Adenosine receptor antagonist 7 shows potent inhibitory activity (IC₅₀ = 0.8 nM) of cAMP production in A2AR-HEK293 cells. Adenosine receptor antagonist 7 can enhance infiltration of effector T cells and increase the CD8+/Treg ratio companied with Avelumab (HY-108730). Adenosine receptor antagonist 7can be used for the research of cancer, such as colon cancer.

A2AAR antagonist 4 is an orally active A_2A Adenosine receptor antagonist with a K_i of 0.36 nM and a K_B of 1 nM at hA_2AAR. A2AAR antagonist 4 fully inhibits hA_2AAR and hA_2bAR at 10 μM. A2AAR antagonist 4 can be used for research of cancer, such as MC38 tiumor.

A3AR antagonist 3 (compound 21) is a selective A3 adenosine receptor (A3AR) antagonist with a K_i of 37 nM. A3AR antagonist 3 shows >60-fold selectivity in comparison to A1 and A2A adenosine receptors.

MK-1088 is an orally active A_2A/A_2B adenosine receptor antagonist with human A_2A K_i of 0.31 nM, human A_2B K_i 5.3 nM. MK-1088 blocks receptor downstream signaling, inhibits CREB phosphorylation and reverses adenosine-mediated immunosuppression. MK-1088 restores TNF−α release and enhances tumor immune surveillance. MK-1088 can be used for the research of cancer^[1].

ATL444 is a adenosine receptor antagonist, with K_i values of 7.0, 2.5, 61.8, >1000 nM for rA₁AR, rA_2AAR, rA_2BAR, rA₃AR, respectively.

hA2A/hCA XII modulator 1 (compound 14), a triazolopirazine, is a potent hA_2A adenosine receptor (hA_2AAR) antagonist with K_is of 6.4 nM, 4.819 μM, >30 μM for hA_2AAR, hA₁AR, hA₃AR, respectively. hA2A/hCA XII modulator 1 is a potent human carbonic anhydrase XII (hCA XII) inhibitor with K_is of 6.2 nM, 46 nM, 466 nM, 8.351 μM for hCA XII, hCA II, hCA IX and hCA I, respectively. hA2A/hCA XII modulator 1 has the potential for cancer research.

LUF5437 is a potent and selective adenosine A₁ receptor antagonist with a rat K_i of 7.3 nM. LUF5437 can be used for research on cardiovascular and neurological diseases.

Adenosine receptor antagonist 6 is an orally active and selective A_2A adenosine receptor (A_2AAR) antagonist, with a K_i of 19.18 nM. Adenosine receptor antagonist 6 inhibits 5’-N-ethylcarboxamide adenosine (NECA) (HY-103173)-mediated cAMP production (IC₅₀ = 0.089 μM) and immunosuppression, while promoting IL-2 and IFN-γ secretion. Adenosine receptor antagonist 6 abolishes the immunosuppressive effects of adenosine on T-cell activation and cytokine release. Adenosine receptor antagonist 6 inhibits tumor growth in a CT26/MC38 xenograft model. Adenosine receptor antagonist 6 can be used for the study of colon cancer.