CN1303289A - 腺苷a3受体调节剂 - Google Patents
腺苷a3受体调节剂 Download PDFInfo
- Publication number
- CN1303289A CN1303289A CN99806594A CN99806594A CN1303289A CN 1303289 A CN1303289 A CN 1303289A CN 99806594 A CN99806594 A CN 99806594A CN 99806594 A CN99806594 A CN 99806594A CN 1303289 A CN1303289 A CN 1303289A
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- Prior art keywords
- amino
- chemical compound
- alkyl
- furyl
- triazol
- Prior art date
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- 102000008161 Adenosine A3 Receptor Human genes 0.000 title description 2
- 108010060261 Adenosine A3 Receptor Proteins 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 227
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims abstract description 58
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims abstract description 35
- 229960005305 adenosine Drugs 0.000 claims abstract description 29
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 2
- -1 imidazole radicals Chemical class 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 238000006243 chemical reaction Methods 0.000 claims description 44
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- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
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- 239000001257 hydrogen Substances 0.000 claims description 13
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
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- 125000004104 aryloxy group Chemical group 0.000 claims description 5
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 4
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- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
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- VYSAWGWSQKKQEH-UHFFFAOYSA-N imidazo[4,5-d]triazole;pyrimidine Chemical class C1=CN=CN=C1.N1=NC2=NC=NC2=N1 VYSAWGWSQKKQEH-UHFFFAOYSA-N 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
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- 239000003018 immunosuppressive agent Substances 0.000 description 1
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- 230000001939 inductive effect Effects 0.000 description 1
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
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- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- POPRCUFMXZJTQI-UHFFFAOYSA-N oxomethanedisulfonic acid Chemical group OS(=O)(=O)C(=O)S(O)(=O)=O POPRCUFMXZJTQI-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
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- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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Abstract
Description
化合物编号 | R | R1 |
60 | H | H |
61 | H | 4-MeO-Ph-NHCO |
62 | H | 3-Cl-Ph-NHCO |
63 | t-C4H9 | H |
64 | t-C4H9 | 4-MeO-Ph-NHCO |
65 | t-C4H9 | 3-Cl-Ph-NHCO |
66 | CH3 | Ph-NHCO |
67 | CH3 | 4-SO3H-Ph-NHCO |
68 | CH3 | 3,4-Cl2-Ph-NHCO |
69 | CH3 | 3,4-(OCH2-O)-Ph-NHCO |
70 | CH3 | 4-(NO2)-Ph-NHCO |
71 | CH3 | 4-(CH3)-Ph-NHCO |
72 | CH3 | Ph-(CH2)-CO |
73 | C2H5 | Ph-NHCO |
74 | C2H5 | 4-SO3H-Ph-NHCO |
75 | C2H5 | 3,4-Cl2-Ph-NHCO |
76 | C2H5 | 3,4-(OCH2-O)-Ph-NHCO |
77 | C2H5 | 4-(NO2)-Ph-NHCO |
78 | C2H5 | 4-(CH3)-Ph-NHCO |
79 | C2H5 | Ph-(CH2)-CO |
80 | n-C3H7 | Ph-NHCO |
81 | n-C3H7 | 4-SO3H-Ph-NHCO |
82 | n-C3H7 | 3,4-Cl2-Ph-NHCO |
83 | n-C3H7 | 3,4-(OCH2-O)-Ph-NHCO |
84 | n-C3H7 | 4-(NO2)-Ph-NHCO |
85 | n-C3H7 | 4-(CH3)-Ph-NHCO |
86 | n-C3H7 | Ph-(CH2)-CO |
87 | n-C4H9 | Ph-NHCO |
88 | n-C4H9 | 4-SO3H-Ph-NHCO |
89 | n-C4H9 | 3,4-Cl2-Ph-NHCO |
90 | n-C4H9 | 3,4-(OCH2-O)-Ph-NHCO |
91 | n-C4H9 | 4-(NO2)-Ph-NHCO |
92 | n-C4H9 | 4-(CH3)-Ph-NHCO |
93 | 2-(α-萘基)乙基 | Ph-(CH2)-CO |
94 | 2-(α-萘基)乙基 | H |
95 | 2-(α-萘基)乙基 | 4-MeO-Ph-NHCO |
96 | 2-(α-萘基)乙基 | 3-Cl-Ph-NHCO |
97 | 2-(2,4,5-三溴苯基)乙基 | H |
98 | 2-(2,4,5-三溴苯基)乙基 | 4-MeO-Ph-NHCO |
99 | 2-(2,4,5-三溴苯基)乙基 | 3-Cl-Ph-NHCO |
100 | 2-丙烯-1-基 | 4-MeO-Ph-NHCO |
化合物 | R | R1 | rA1(K1,nM) | rA2A(Ki,nM) | hA3(Ki,nM) | rA1/hA3 | rA2A/hA3 |
MRS 1220* | 305±51 | 52±8.8 | 0.65±0.25 | 470 | 80 | ||
34 | CH3 | H | 313(286-342) | 30.65(28.62-32.82) | 557(489-636) | 0.56 | 0.05 |
43 | CH3 | 4-MeO-Ph-NHCO | <10,000 | >10,000 | 0.10(0.09-0.11) | >100,000 | >100,000 |
42 | CH3 | 3-Cl-Ph-NHCO | 5,045(4,566-5,579) | >10,000 | 0.22(0.20-0.25) | 22,931 | >45,454 |
35 | CH3CH2 | H | 95,09(86.76-104.22) | 11.15(9.84-12.63) | 3,579(3,376-3,793) | 0.03 | 0.003 |
45 | CH3CH2 | 4-MeO-Ph-NHCO | >10.000 | >10,000 | 0.28(0.25-0.32) | >35,714 | >35,714 |
44 | CH3CH2 | 3-Cl-Ph-NHCO | 2,699(2,521-2,889) | 2,799(2,621-2,989) | 2.09(1.9-2.31) | 1,291 | 1,339 |
36 | CH3CH2CH2 | H | 139(107-181) | 20.23(16.14-25.36) | 613(582-646) | 0.22 | 0.03 |
47 | CH3CH2-CH2 | 4-MeO-Ph-NHCO | >10,000 | 1,993(1,658-2,397 | 0.29(0.27-0.32) | >34,482 | 6,872 |
46 | CH3CH2-CH2 | 3-Cl-Ph-NHCO | 1,582(1,447-1,730) | <10,000 | 0.49(0.47-0.52) | 3,228 | >20,408 |
37 | CH3CH2CH2-CH2 | H | 26.30(23.66-29.24) | 4.20(3.84-4.58) | 1,109(981-1,254) | 0.02 | 0.003 |
49 | CH3CH2CH2-CH2 | 4-Me0-Ph-NHCO | 2,098(1,923-2,290) | 649(563-747) | 0.30(0.26-0.34) | 6,993 | 2,163 |
48 | CH3CH2CH2-CH2 | 3-Cl-Ph-NHCO | 1,515(1,382-1,661) | 498(414-599) | 0.75(0.65-0.86) | 2,020 | 664 |
38 | (CH2)2CH-CH2-CH2- | H | 8.09(7.46-8.78) | 1.20(1.03-1.40) | 1,163(1,024-1,320) | 0.007 | 0.001 |
51 | (CH3)2CH-CH2-CH2- | 4-MeO-Ph-NHCO | 476(432-525) | 376(332-426) | 29.57(26.94-32.46) | 16 | 13 |
50 | (CH3)2CH-CH2-CH2- | 3-Cl-Ph-NHCO | 1,650(1,560-1,744) | 1,197(1,027-1,396) | 81.10(68.45-96.09) | 20 | 15 |
58 | (CH3)2CH-CH2-CH2- | Ph-CH2CO | 373(330-422) | 323(280-372) | 81.10(68.45-96.09) | 4.6 | 4 |
39 | (CH3)2C=CH-CH2- | H | 10.08(8.63-11.76) | 1.45(1.36-1.54) | 887(761-1034) | 0.01 | 0.001 |
53 | (CH3)2C=CH-CH2- | 4-MeO-Ph-NHCO | 5,296(4,826-5,811) | >10,000 | 29.57(26.94-32.46) | 179 | >338 |
52 | (CH3)2C=CH-CH2- | 3-Cl-Ph-NHCO | 3,744(3,312-4,233) | 1,453(1,363-1,549) | 147(122-178) | 25.4 | 9.8 |
40 | Ph-CH2-CH2 | H | 2.16(1.9-2.47) | 0.70(0.53-0.91) | 2,785(2,463-3,149) | 0.0007 | 0.0002 |
55 | Ph-CH2-CH2 | 4-MeO-Ph-NHCO | 1,282(1,148-1,432) | 1,398(1,225-1,594) | 1.47(1.22-1.78) | 872 | 951 |
54 | Ph-CH2-CH2 | 3-Cl-Ph-NHCO | 1,049(961-1,145) | 1,698(1,524-1,892) | 13.28(10.87-16.23) | 79 | 128 |
41 | Ph-CH2-CH2-CH2 | H | 11.13(9.34-13.27) | 0.59(0.44-0.81) | 2,666(2,533-2,805) | 0.004 | 0.0002 |
57 | Ph-CH2-CH2-CH2 | 4-MeO-Ph-NHCO | 1,514(1,332-1,721) | >10,OOO | 19.81(17.61-22.27) | 76.4 | >504 |
56 | Ph-CH2-CH2-CH2 | 3-Cl-Ph-NHCO | >10,000 | 3,200(3,025-3,385) | 42.65(39.92-45.57) | >234 | 75 |
59 | Ph-CH2-CH2-CH2 | Ph-CH2CO | 345(313-379) | 400(365-438) | 121(102-143) | 2.8 | 3.3 |
细胞系 | 总结合 | 非特异性结合 | 特异性结合(cpm) | 特异性结合百分数 |
HL 60 | 3484 | 2791 | 693 | 20 |
NB4 | 3377 | 2740 | 637 | 19 |
SKN-MC | 7528 | 6220 | 1308 | 17 |
SKN-Be2C | 6000 | 4585 | 1415 | 24 |
SKN-SH | 2671 | 2580 | 91 | 3 |
JURKAT | 7599 | 4753 | 2846 | 38 |
组分 | 含量 |
活性化合物硅氧烷液体胶体二氧化硅 | 100g450g2g |
组分 | 含量 |
活性化合物淀粉硬脂酸镁 | 50g50g5g |
组分 | 含量 |
活性化合物缓冲剂丙二醇注射用水 | 10g适量400mg适量,加至1000ml |
组分 | 含量 |
活性化合物缓冲剂注射用水 | 10g适量适量,加至1000ml |
Claims (19)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
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US09/154,435 US6448253B1 (en) | 1998-09-16 | 1998-09-16 | Adenosine A3 receptor modulators |
US09/154,435 | 1998-09-16 | ||
US09/379,300 | 1999-08-23 | ||
US09/379,300 US6407236B1 (en) | 1998-09-16 | 1999-08-23 | Adenosine A3 receptor modulators |
Publications (2)
Publication Number | Publication Date |
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CN1303289A true CN1303289A (zh) | 2001-07-11 |
CN1154494C CN1154494C (zh) | 2004-06-23 |
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CNB998065943A Expired - Fee Related CN1154494C (zh) | 1998-09-16 | 1999-09-15 | 腺苷a3受体调节剂 |
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Country | Link |
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US (2) | US6448253B1 (zh) |
JP (1) | JP2002524519A (zh) |
KR (1) | KR100448555B1 (zh) |
CN (1) | CN1154494C (zh) |
AT (2) | AT414240B (zh) |
AU (1) | AU749211B2 (zh) |
BR (1) | BR9913766A (zh) |
CA (1) | CA2332007C (zh) |
CH (1) | CH692132A5 (zh) |
DE (1) | DE19983530T1 (zh) |
DK (1) | DK200100432A (zh) |
ES (1) | ES2204262B1 (zh) |
FI (1) | FI116624B (zh) |
GB (1) | GB2353527B (zh) |
HK (1) | HK1035671A1 (zh) |
HU (1) | HUP0102589A3 (zh) |
ID (1) | ID28100A (zh) |
IL (1) | IL156851A (zh) |
LU (1) | LU90687B1 (zh) |
NO (1) | NO318078B1 (zh) |
NZ (1) | NZ509149A (zh) |
RO (1) | RO121030B1 (zh) |
RU (1) | RU2250904C2 (zh) |
SE (1) | SE522578C2 (zh) |
TR (1) | TR200003461T2 (zh) |
WO (1) | WO2000015231A1 (zh) |
YU (1) | YU83600A (zh) |
ZA (1) | ZA200101626B (zh) |
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CN111004245A (zh) * | 2019-12-11 | 2020-04-14 | 徐州医科大学 | 吡唑-嘧啶并咪唑类化合物、制备方法及其应用 |
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-
1998
- 1998-09-16 US US09/154,435 patent/US6448253B1/en not_active Expired - Lifetime
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- 1999-09-15 AT AT0904399A patent/AT414240B/de not_active IP Right Cessation
- 1999-09-15 RO ROA200001172A patent/RO121030B1/ro unknown
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- 1999-09-15 RU RU2000127721/15A patent/RU2250904C2/ru not_active IP Right Cessation
- 1999-09-15 CN CNB998065943A patent/CN1154494C/zh not_active Expired - Fee Related
- 1999-09-15 DE DE19983530T patent/DE19983530T1/de not_active Withdrawn
- 1999-09-15 JP JP2000569815A patent/JP2002524519A/ja not_active Abandoned
- 1999-09-15 TR TR2000/03461T patent/TR200003461T2/xx unknown
- 1999-09-15 NZ NZ509149A patent/NZ509149A/en unknown
- 1999-09-15 GB GB0027879A patent/GB2353527B/en not_active Expired - Fee Related
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- 1999-09-15 BR BR9913766-6A patent/BR9913766A/pt not_active Application Discontinuation
- 1999-09-15 AU AU62482/99A patent/AU749211B2/en not_active Ceased
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Cited By (2)
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CN111004245A (zh) * | 2019-12-11 | 2020-04-14 | 徐州医科大学 | 吡唑-嘧啶并咪唑类化合物、制备方法及其应用 |
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