源自组胺H2受体拮抗剂西咪替丁组的组胺H1受体拮抗剂的结构。
Structures of histamine H1-receptor antagonists derived from the cimetidine group of histamine H2-receptor antagonists.
作者信息
Bannister C, Burns K, Prout K, Watkin D J, Cooper D G, Duránt G J, Ganellin C R, Ife R J, Sach G S
机构信息
Chemical Crystallography Laboratory, Oxford University, England.
出版信息
Acta Crystallogr B. 1994 Apr 1;50 ( Pt 2):221-43. doi: 10.1107/s0108768193010407.
The crystal and molecular structures of ten compounds with strong structural resemblances to the cimetidine group of histamine H2-receptor antagonists, but exhibiting selective H1-receptor antagonist activity, (1)-(7), or H1 and H2 activity (8)-(10), have been determined: (1) 2-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-5- (6-methyl-3-pyridylmethyl)-4-pyrimidone trihydrobromide (temalastine), C21H27BrN5O3+.3Br-, M(r) = 685.09, triclinic, P1, a = 6.314 (2), b = 11.192 (2), c = 19.441 (5) A, alpha = 102.47 (2), beta = 92.77 (2), gamma = 103.28 (2) degrees, V = 1298.51 A3, Z = 2, Dx = 1.75 g cm-3, mu = 61.6 cm-1, F(000) = 672, R = 2.93% for 3208 independent reflexions. (2) 2-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4-pyrimidone, C14H19BrN4O2, M(r) = 355.23, monoclinic, I2/a, a = 16.359 (3), b = 10.469 (6), c = 18.339 (4) A, beta = 90.90 (2) degrees, V = 3140.49 A3, Z = 8, Dx = 1.503 g cm-3, mu = 26.0 cm-1, F(000) = 1176, R = 4.2% for 1872 independent reflexions. (3) 3-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4- amino-1,2,5-thiadiazole-1-oxide, C12H16BrN5OS, M(r) = 358.26, triclinic, P1, a = 14.295 (2), b = 12.447 (2), c = 9.917 (2) A, alpha = 95.77 (2), beta = 113.86 (2), gamma = 106.91 (1) degrees, V = 1495.18 A3, Z = 4, Dx = 1.59 g cm-3, mu = 50.96 cm-1, F(000) = 728, R = 5.98% for 5674 independent reflexions. (4) 3-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4- benzylamino-1,2,5-thiadiazole-1-oxide, C19H22BrN5OS, M(r) = 448.38, monoclinic, P2(1)/c, a = 36.293 (7), b = 4.826 (2), c = 11.528 (3) A, beta = 96.91 (2) degrees, V = 2004.27 A3, Z = 4, Dx = 1.49 g cm-3, mu = 39.2 cm-1, F(000) = 920, R = 12.1% for 1945 independent reflexions. (5) 2-[3-(N-Benzyl-N-2- pyridylamino)propylamino]-4-pyrimidone, C19H21N5O, M(r) = 335.4, orthorhombic, Pbna, a = 7.082 (1), b = 19.889 (3), c = 24.899 (3) A, V = 3507.16 A3, Z = 8, Dx = 1.27 g cm-3, mu = 6.24 cm-1, F(000) = 1424, R = 4.05% from 2470 independent reflexions. (6) 3-[3-(N-4-Fluorobenzyl-N-2- pyridylamino)propylamino]-4-ethylamino-1,2,5-thiadiazole-1-oxide, C19H23FN6OS, M(r) = 402.5, monoclinic, P2(1)/n, a = 6.686 (2), b = 14.717 (3), c = 20.850 (5) A, beta = 97.83 (2) degrees, V = 2032.47 A3, Z = 4, Dx = 1.32 g cm-3, mu = 16.41 cm-1, F(000) = 848, R = 8.5% from 2484 independent reflexions. (7) 5-(6-Methyl-3-pyridylmethyl)-2-[3-(5,6,7,8-tetrahydro-8- quinolyl)propylamino]-4-pyrimidone, C23H29N5O2, M(r) = 407.5, monoclinic, P2(1)/c, a = 14.966 (2), b = 16.075 (2), c = 9.1608 (9) A, beta = 99.158 (8) degrees, V = 2175.83 A3, Z = 4, Dx = 1.24 g cm-3, mu = 6.19 cm-1; F(000) = 872, R = 5.3% from 2784 independent reflexions. (8) 2-(4-Phenylbutylamino)-5-(3-pyridyl-methyl)-4-pyrimidone, C20H26N4O3, M(r) = 370.5, monoclinic, P2(1)/c, a = 8.040 (4), b = 21.279 (4), c = 11.404 (2) A, beta = 92.08 (5) degrees, V = 1949.68 A3, Z = 4, Dx = 1.26 g cm-3, mu = 0.93 cm-1, F(000) = 792, R = 4.05% from 3816 independent reflexions.(ABSTRACT TRUNCATED AT 400 WORDS)
已确定了十种化合物的晶体结构和分子结构，这些化合物与组胺H2受体拮抗剂西咪替丁基团有很强的结构相似性，但表现出选择性H1受体拮抗剂活性（1）-（7），或H1和H2活性（8）-（10）：（1）2-[4-(5-溴-3-甲基-2-吡啶基)丁基氨基]-5-(6-甲基-3-吡啶基甲基)-4-嘧啶酮三氢溴酸盐（替马司汀），C21H27BrN5O3+.3Br-，M(r)=685.09，三斜晶系，P1，a = 6.314(2)，b = 11.192(2)，c = 19.441(5)Å，α = 102.47(2)，β = 92.77(2)，γ = 103.28(2)°，V = 1298.51Å3，Z = 2，Dx = 1.75 g cm-3，μ = 61.6 cm-1，F(000)=672，对于3208个独立反射，R = 2.93%。（2）2-[4-(5-溴-3-甲基-2-吡啶基)丁基氨基]-4-嘧啶酮，C14H19BrN4O2，M(r)=355.23，单斜晶系，I2/a，a = 16.359(3)，b = 10.469(6)，c = 18.339(4)Å，β = 90.90(2)°，V = 3140.49Å3，Z = 8，Dx = 1.503 g cm-3，μ = 26.0 cm-1，F(000)=1176，对于1872个独立反射，R = 4.2%。（3）3-[4-(5-溴-3-甲基-2-吡啶基)丁基氨基]-4-氨基-1,2,5-噻二唑-1-氧化物，C12H16BrN5OS，M(r)=358.26，三斜晶系，P1，a = 14.295(2)，b = 12.447(2)，c = 9.917(2)Å，α = 95.77(2)，β = 113.86(2)，γ = 106.91(1)°，V = 1495.18Å3，Z = 4，Dx = 1.59 g cm-3，μ = 50.96 cm-1，F(000)=728，对于5674个独立反射，R = 5.98%。（4）3-[4-(5-溴-3-甲基-2-吡啶基)丁基氨基]-4-苄基氨基-1,2,5-噻二唑-1-氧化物，C19H22BrN5OS，M(r)=448.38，单斜晶系，P2(1)/c，a = 36.293(7)，b = 4.826(2)，c = 11.528(3)Å，β = 96.91(2)°，V = 2004.27Å3，Z = 4，Dx = 1.49 g cm-3，μ = 39.2 cm-1，F(000)=920，对于1945个独立反射，R = 12.1%。（5）2-[3-(N-苄基-N-2-吡啶基氨基)丙基氨基]-4-嘧啶酮，C19H21N5O，M(r)=335.4，正交晶系，Pbna，a = 7.082(1)，b = 19.889(3)，c = 24.899(3)Å，V = 3507.16Å3，Z = 8，Dx = 1.27 g cm-3，μ = 6.24 cm-1，F(000)=1424，对于2470个独立反射，R = 4.05%。（6）3-[3-(N-4-氟苄基-N-2-吡啶基氨基)丙基氨基]-4-乙氨基-1,2,5-噻二唑-1-氧化物，C19H23FN6OS，M(r)=402.5，单斜晶系，P2(1)/n，a = 6.686(2)，b = 14.717(3)，c = 20.850(5)Å，β = 97.83(2)°，V = 2032.47Å3，Z = 4，Dx = 1.32 g cm-3，μ = 16.41 cm-1，F(000)=848，对于2484个独立反射，R = 8.5%。（7）5-(6-甲基-3-吡啶基甲基)-2-[3-(5,6,7,8-四氢-8-喹啉基)丙基氨基]-4-嘧啶酮，C23H29N5O2，M(r)=407.5，单斜晶系，P2(1)/c，a = 14.966(2)，b = 16.075(2)，c = 9.1608(9)Å，β = 99.158(8)°，V = 2175.83Å3，Z = 4，Dx = 1.24 g cm-3，μ = 6.19 cm-1；F(000)=872，对于2784个独立反射，R = 5.3%。（8）2-(4-苯基丁基氨基)-5-(3-吡啶基甲基)-4-嘧啶酮，C20H26N4O3，M(r)=370.5，单斜晶系，P2(1)/c，a = 8.040(4)，b = 21.279(4)，c = 11.404(2)Å，β = 92.08(5)°，V = 1949.68Å3，Z = 4，Dx = 1.26 g cm-3，μ = 0.93 cm-1，F(000)=792，对于3816个独立反射，R = 4.05%。（摘要截断于400字）
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