TDI-11861

TDI-11861 is an inhibitor of soluble adenylyl cyclase (sAC, IC50 = 3.3 nM), a bicarbonate-regulated cytosolic enzyme also known as AC10. It is selective for sAC over the transmembrane ACs (tmACs) AC1, AC2, AC5, AC8, and AC9 at 100 nM, a panel of 322 kinases (IC50s = >1,000 nM for all), and 46 other targets, including G protein-coupled receptors (GPCRs), nuclear receptors, and ion channels, with 50% response concentration values (RC50s) of greater than 9 µM. TDI-11861 has an increased residence time when binding to sAC in a surface plasmon resonance (SPR) assay and a slower dissociation rate in a jump dilution recovery assay compared with the sAC inhibitor TDI-10229 (Cay-37674), indicating a lower risk of post-copulation female genital tract dilution. It inhibits capacitation-induced cAMP accumulation in isolated mouse and human sperm when used at a concentration of 5 µM and reduces sodium bicarbonate-induced increases in mouse and human sperm beat frequency. Oral administration of a single dose of TDI-11861 (50 mg/kg) induces temporary infertility in male mice without affecting mating behavior.Formal Name: (3R)-4-[2-[2-[[3-(2-amino-6-chloro-4-pyrimidinyl)-1-(difluoromethyl)-1H-pyrazol-4-yl]methyl]phenoxy]ethyl]-3-morpholinemethanol. CAS Number: 2857049-72-8. Molecular Formula: C22H25ClF2N6O3. Formula Weight: 494.9. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble. SMILES: NC1=NC(Cl)=CC(C2=NN(C(F)F)C=C2CC3=C(OCCN4[C@H](CO)COCC4)C=CC=C3)=N1. InChi Code: InChI=1S/C22H25ClF2N6O3/c23-19-10-17(27-22(26)28-19)20-15(11-31(29-20)21(24)25)9-14-3-1-2-4-18(14)34-8-6-30-5-7-33-13-16(30)12-32/h1-4,10-11,16,21,32H,5-9,12-13H2,(H2,26,27,28)/t16-/m1/s1. InChi Key: XVGSKZXXLKUEIO-MRXNPFEDSA-N.