ChemInform Abstract: STRUCTURE‐ACTIVITY RELATIONS OF HISTAMINE ANALOGS. XXII. ABSOLUTE CONFIGURATION AND HISTAMINE‐LIKE EFFECT OF THE ENANTIOMERIC α,Nα‐DIMETHYLHISTAMINES

Abstract

Wie im Formelschema skizziert, werden das S‐(J‐Dimethylhistamin (VI) und das R‐(+)‐ Dimethylhistamin (VIII) synthetisiert.

Synthesis, X-ray Crystallography, and Pharmacokinetics of Novel Azomethine Prodrugs of (R)-.alpha.-Methylhistamine: Highly Potent and Selective Histamine H3 Receptor Agonists

“…(fi)-(-)-2-[[iV-[l-(lH-Imidazol-4-yl)-2-propyl]imino]phenylmethyl]phenol (9a): method A (yield 35%) or method B (yield 85%); crystallized from EtOAc/CeHX2; -NMR (DMSOde) <3 15.63 (s* 1H, NH), 11.73 (br*, 1H, OH), 7.53 (m, 4H, Ph-2-H, Ph-4-H, Ph-6-H, imidazole-2-H), 7.26 (m, 3H, Ph-3-H, Ph-5-H, HOPh-5-íf), 6.74 (m, 4H, HOPh-3-tf, HOPh-4-H, HOPh-6-H, imidazole-5-H), 3.53 (m, 1H, CH), 2.73 (d, 2H, J = 6, CH2), 1.15 (d, 3H, J = 6, CH3). Anal. (fZ)-(-)-2-[[lV-[l-(lff-Imidazol-4-yl)-2-propyl]immo](2-hydroxyphenyI)methyl]phenol (9b): method A; crystallized from EtOAc/C6Hi2; -NMR (DMSO-d6) 15.77 (br*, 0.64H, NH), 15.65 (br*, 0.36H, NH), 11.75 (br*, 1H, (E)-OH), 9.90 (br*, IH, (Z)-OH), 7.49-6.41 (m, 10 H, 8Ph-H, imidazole-2-H, imidazole-5-H), 3.55 (m, 1H, CH), 2.87-2.69 (m, 2H, CH2), 1.17 (d, 0.64 3H, J = 6.2, CH3), 1.06 (d, 0.36 3H, J = 6.2, CH3). (br*, 1H, Ph-2-OH), 9.92 (s*, 1H, Ph-4-OH), 7.48 (m, 4H, Ph-2-H, Ph-4-H, Ph-6-H, imidazole-2-H), 7.23-6.64 (m, 3H, Ph-3, Ph-5-H, imidazole-5-H), 6.33 (d, 1H, J = 8.7, HOPh-3-), 6.17 .49 (m, 6H, 5Ph-H, imidazole-2-H), 6.63 (s, 1H, imidazole-5-H), 6.41 (d, 1H, J = 8.9, HOPh-3-tf), 6.33 (s, 1H, HOPh-6-JT), 6.41 (d, 1H, J = 8.9, HOPh-4-ií), 3.50 (br*, 1H, OH), 7.52 (m, 4H, Ph-2-H, Ph-4-H, Ph-6-H, imidazole-2-H), 7.17 (m, 1H, HOPh-5-tf), 6.92 (m, 3H, Ph-3-H, Ph-5-H, HOPh-6-fl), 6.64 (s, 1H, imidazole-5-H), 6.23 (m, 1H, HOPh-3-H), 3.53 imino]phenylmethyl]phenol (9g): method B; crystallized from EtOAc/C6HX2; -NMR (DMSO-de) ó 15.81 (s*, 1H, NH), 11.75 (br*, 1H, OH), 7.52 (m, 4H, Ph-2-H, Ph-4-H, Ph-6-H, imidazole-2-H), 7.32 (dd, 1H, 3J = 8.8, 4J = 2.7, HOPh-5-H), 6.94 (m, 3H, Ph-3-H, Ph-5-H, HOPh-6-tf), 6.64 (s, 1H, imidazole-5-H), 6.47 (d, 1H, 4J = 2.7, HOPh-3-H), 3.54 (m, 1H, CH), 2.73 (d, 2H, J = 6.3, CH2), 1.16 (d, 3H, J = 6.4, CH3).…”

Gastric histamine methyltransferase: Different methylation rates for enantiomers of side-chain methylated histamine analogues using a highly purified enzyme preparation

“…stimulated Hrreceptors to the same, but H zreceptors to different extents, the stronger stimulation being always exerted by the Senantiomers [4,5]. If this different action at H2-receptors is mirrored in a different influence on HMT-activity such a finding could support the hypothesis that the active centres of the H 2-receptor and of gastric HMT are similar.…”

Synthesis and in Vitro Pharmacology of a Series of New Chiral Histamine H3-Receptor Ligands: 2-(RandS)-Amino-3-(1H-imidazol-4(5)-yl)propyl Ether Derivatives

“…White crystals were obtained after recrystallization from ethanol/ether (yield 560 mg, 2.62 mmol, 82%): mp 200 °C (lit. 196−198 °C); 1 H and 13 C NMR data were identical to those of compound 20 ; [α] D −2.65 ± 0.04 (SD) (23.3 °C, H 2 O, c = 1); [α] D −2.9 (H 2 O, c = 0.01) . HRMS: m / z 142.0969, calcd for (M + H) + C 6 H 11 N 3 O 142.0980.…”

“…White crystals were obtained (yield 720 mg, 3.36 mmol, 84%): mp 196−197 °C (lit. 196−198 °C 36 ); 1 H NMR (D 2 O) δ 3.20 (m, 2H, Im-C H 2 ), 3.72 (m, 2H, HO-C H 2 ), 3.84 (m, 1H, NH 2 -C H ), 7.46 (s, 1H, Im- 5-H ), 8.72 (s, 1H, Im- 2-H ); 13 C NMR (D 2 O) δ 27.03 (t, HO- C H 2 ), 54.66 (d, H 2 N- C H), 62.95 (t, Im- C H 2 ), 120.71 (d, Im- 5-C H), 130.24 (s, Im- 4-C ), 137.06 (d, Im- 2-C H); [α] D 2.48 ± 0.03 (SD) (23.8 °C, H 2 O, c = 1); 2.9 (H 2 O, c = 0.01) . HRMS: m / z 142.1061, calcd for (M + H) + C 6 H 11 N 3 O 142.0980.…”

“…196-198 °C36 ); 1 H and 13 20 2.9 (H2O, c ) 0.01). 36 HRMS: m/z 142.1061, calcd for (M + H) + C6H11N3O 142.0980. Anal.…”