CA1109872A - Derives de la purine - Google Patents

Derives de la purine

Info

Publication number: CA1109872A
Authority: CA; Canada
Prior art keywords: formula; compound; produce; cyclohexyl; adenine
Prior art date: 1978-05-09
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA370,571A

Other languages

English (en)

Inventor

Takayuki Naito

Haruhiro Yamashita

Tetsuro Yamasaki

Susumu Nakagawa

Taka-Aki Okita

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1978-05-09

Filing date

1981-02-10

Publication date

1981-09-29

1978-05-09 Priority claimed from US05/904,146 external-priority patent/US4172829A/en

1981-02-10 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1981-02-10 Priority to CA370,571A priority Critical patent/CA1109872A/fr

1981-09-29 Application granted granted Critical

1981-09-29 Publication of CA1109872A publication Critical patent/CA1109872A/fr

Status Expired legal-status Critical Current

Links

229940083251 peripheral vasodilators purine derivative Drugs 0.000 title abstract 2
125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 44
150000003839 salts Chemical class 0.000 claims abstract description 29
239000002253 acid Substances 0.000 claims abstract description 17
238000004519 manufacturing process Methods 0.000 claims abstract description 3
238000000034 method Methods 0.000 claims description 39
-1 cyclohexyl halide Chemical class 0.000 claims description 19
239000012442 inert solvent Substances 0.000 claims description 16
RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 claims description 14
229910052751 metal Inorganic materials 0.000 claims description 13
239000002184 metal Substances 0.000 claims description 13
230000008569 process Effects 0.000 claims description 9
229910052708 sodium Inorganic materials 0.000 claims description 9
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
229910052700 potassium Inorganic materials 0.000 claims description 8
238000005576 amination reaction Methods 0.000 claims description 7
239000003960 organic solvent Substances 0.000 claims description 7
125000001246 bromo group Chemical group Br* 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
125000002346 iodo group Chemical group I* 0.000 claims description 6
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
RCTYPNKXASFOBE-UHFFFAOYSA-M chloromercury Chemical group [Hg]Cl RCTYPNKXASFOBE-UHFFFAOYSA-M 0.000 claims description 3
239000000126 substance Substances 0.000 claims description 2
229910052716 thallium Inorganic materials 0.000 claims description 2
LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 claims 2
229910052709 silver Inorganic materials 0.000 claims 1
229940124630 bronchodilator Drugs 0.000 abstract description 13
239000000168 bronchodilator agent Substances 0.000 abstract description 4
230000001129 nonadrenergic effect Effects 0.000 abstract description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
239000000047 product Substances 0.000 description 27
239000000543 intermediate Substances 0.000 description 24
239000000243 solution Substances 0.000 description 20
229960000643 adenine Drugs 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000000203 mixture Substances 0.000 description 15
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
101150041968 CDC13 gene Proteins 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
125000000753 cycloalkyl group Chemical group 0.000 description 9
230000000694 effects Effects 0.000 description 9
239000011734 sodium Substances 0.000 description 8
FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 7
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
125000000217 alkyl group Chemical group 0.000 description 6
229960003556 aminophylline Drugs 0.000 description 6
239000012458 free base Substances 0.000 description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
230000002526 effect on cardiovascular system Effects 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
150000002500 ions Chemical class 0.000 description 5
239000011591 potassium Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
239000008279 sol Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
229910052720 vanadium Inorganic materials 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
208000006673 asthma Diseases 0.000 description 4
239000002585 base Substances 0.000 description 4
244000309464 bull Species 0.000 description 4
125000005059 halophenyl group Chemical group 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
230000001077 hypotensive effect Effects 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000002904 solvent Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
XSFWDHONRBZVEJ-UHFFFAOYSA-N 7-[3-[[2-(3,5-dihydroxyphenyl)-2-hydroxyethyl]amino]propyl]-1,3-dimethylpurine-2,6-dione;hydron;chloride Chemical compound Cl.C1=2C(=O)N(C)C(=O)N(C)C=2N=CN1CCCNCC(O)C1=CC(O)=CC(O)=C1 XSFWDHONRBZVEJ-UHFFFAOYSA-N 0.000 description 3
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical class NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000000443 aerosol Substances 0.000 description 3
150000004703 alkoxides Chemical class 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
150000001602 bicycloalkyls Chemical group 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
229910000069 nitrogen hydride Inorganic materials 0.000 description 3
230000004044 response Effects 0.000 description 3
ZLUSCZLCHQSJRU-UHFFFAOYSA-N thallium(1+) Chemical compound [Tl+] ZLUSCZLCHQSJRU-UHFFFAOYSA-N 0.000 description 3
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
FCODSIQKLKDEBK-UHFFFAOYSA-N 2-butoxy-9-cyclohexylpurin-6-amine Chemical compound C12=NC(OCCCC)=NC(N)=C2N=CN1C1CCCCC1 FCODSIQKLKDEBK-UHFFFAOYSA-N 0.000 description 2
AYVHHXZXJWFOBE-UHFFFAOYSA-N 2-chloro-9-cyclohex-2-en-1-ylpurin-6-amine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1C1CCCC=C1 AYVHHXZXJWFOBE-UHFFFAOYSA-N 0.000 description 2
PVASNXZESHWYPC-UHFFFAOYSA-N 2-chloro-9-cyclohexylpurin-6-amine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1C1CCCCC1 PVASNXZESHWYPC-UHFFFAOYSA-N 0.000 description 2
AJKDUJRRWLQXHM-UHFFFAOYSA-N 3-bromocyclohexene Chemical compound BrC1CCCC=C1 AJKDUJRRWLQXHM-UHFFFAOYSA-N 0.000 description 2
BCPNLBRDCZWAOW-UHFFFAOYSA-N 9-cyclohex-2-en-1-yl-2-ethoxypurin-6-amine Chemical compound C12=NC(OCC)=NC(N)=C2N=CN1C1CCCC=C1 BCPNLBRDCZWAOW-UHFFFAOYSA-N 0.000 description 2
229930024421 Adenine Natural products 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
208000001953 Hypotension Diseases 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
238000009835 boiling Methods 0.000 description 2
230000003182 bronchodilatating effect Effects 0.000 description 2
239000002775 capsule Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
125000005350 hydroxycycloalkyl group Chemical group 0.000 description 2
208000021822 hypotensive Diseases 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
229940039009 isoproterenol Drugs 0.000 description 2
239000007788 liquid Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000000926 separation method Methods 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
238000003756 stirring Methods 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000006188 syrup Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
239000008096 xylene Substances 0.000 description 2
DVXUCYKBTSDCOI-UHFFFAOYSA-N 2,6-dichloro-7h-purine;silver Chemical compound [Ag].ClC1=NC(Cl)=C2NC=NC2=N1 DVXUCYKBTSDCOI-UHFFFAOYSA-N 0.000 description 1
MBEVSMZJMIQVBG-UHFFFAOYSA-N 2-(hydroxymethyl)guanidine Chemical class NC(N)=NCO MBEVSMZJMIQVBG-UHFFFAOYSA-N 0.000 description 1
SVIDBLFKNZYMSQ-UHFFFAOYSA-N 2-butoxy-9-cyclohex-2-en-1-ylpurin-6-amine Chemical compound C12=NC(OCCCC)=NC(N)=C2N=CN1C1CCCC=C1 SVIDBLFKNZYMSQ-UHFFFAOYSA-N 0.000 description 1
LTESOZAUMTUKQX-UUOKFMHZSA-N 6-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-purine-2-thione Chemical compound C1=NC2=C(N)NC(=S)N=C2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O LTESOZAUMTUKQX-UUOKFMHZSA-N 0.000 description 1
UZFGEUYUBSBADQ-UHFFFAOYSA-N 9-cyclohex-2-en-1-yl-2-(2-methylpropoxy)purin-6-amine Chemical compound C12=NC(OCC(C)C)=NC(N)=C2N=CN1C1CCCC=C1 UZFGEUYUBSBADQ-UHFFFAOYSA-N 0.000 description 1
DONZXFYPODDITG-UHFFFAOYSA-N 9-cyclohex-2-en-1-yl-2-hexoxypurin-6-amine Chemical compound C12=NC(OCCCCCC)=NC(N)=C2N=CN1C1CCCC=C1 DONZXFYPODDITG-UHFFFAOYSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000009079 Bronchial Spasm Diseases 0.000 description 1
208000014181 Bronchial disease Diseases 0.000 description 1
206010006482 Bronchospasm Diseases 0.000 description 1
XUPTVKORAROJNP-UHFFFAOYSA-N C(CCCCC)OCCCCCC.[Na] Chemical compound C(CCCCC)OCCCCCC.[Na] XUPTVKORAROJNP-UHFFFAOYSA-N 0.000 description 1
208000014085 Chronic respiratory disease Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 description 1
206010053155 Epigastric discomfort Diseases 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
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240000000037 Prosopis spicigera Species 0.000 description 1
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229910019020 PtO2 Inorganic materials 0.000 description 1
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
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230000009471 action Effects 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000001118 alkylidene group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
201000009961 allergic asthma Diseases 0.000 description 1
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
230000004872 arterial blood pressure Effects 0.000 description 1
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000008280 blood Substances 0.000 description 1
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229910052794 bromium Inorganic materials 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
229960001231 choline Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000000392 cycloalkenyl group Chemical group 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
230000000916 dilatatory effect Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
SDIXRDNYIMOKSG-UHFFFAOYSA-L disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
DZFYOYRNBGNPJW-UHFFFAOYSA-N ethoxythallium Chemical compound [Tl+].CC[O-] DZFYOYRNBGNPJW-UHFFFAOYSA-N 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
229960001340 histamine Drugs 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 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
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 description 1
239000002777 nucleoside Substances 0.000 description 1
150000003833 nucleoside derivatives Chemical class 0.000 description 1
229940099990 ogen Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
238000010998 test method Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000009423 ventilation Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA370,571A 1978-05-09 1981-02-10 Derives de la purine Expired CA1109872A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA370,571A CA1109872A (fr)	1978-05-09	1981-02-10	Derives de la purine

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US05/904,146 US4172829A (en)	1978-05-09	1978-05-09	2,9-Disubstituted adenine derivatives and their use as non-adrenergic bronchodilators
CA327,184A CA1109871A (fr)	1978-05-09	1979-05-08	Derives de la purine
CA370,571A CA1109872A (fr)	1978-05-09	1981-02-10	Derives de la purine
US904,146		1986-09-05

Publications (1)

Publication Number	Publication Date
CA1109872A true CA1109872A (fr)	1981-09-29

Family

ID=27166227

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA370,571A Expired CA1109872A (fr)	1978-05-09	1981-02-10	Derives de la purine

Country Status (1)

Country	Link
CA (1)	CA1109872A (fr)

1981
- 1981-02-10 CA CA370,571A patent/CA1109872A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1998-09-29	MKEX	Expiry

Publication	Publication Date	Title
US4201860A (en)	1980-05-06	Purine derivatives
SU1598865A3 (ru)	1990-10-07	Способ получени 3-арилокси-3-замещенных пропанаминов или их фармакологически приемлемых кислотно-аддитивных солей
CA1109871A (fr)	1981-09-29	Derives de la purine
EP0103497B1 (fr)	1986-01-29	Nouveaux dérivés de la xanthine, leur procédé de préparation et les compositions pharmaceutiques les renfermant
CZ286230B6 (cs)	2000-02-16	Nové xanthinové deriváty a způsob jejich výroby
SU1597096A3 (ru)	1990-09-30	Способ получени производных дифенилпропиламина или их фармакологически приемлемых солей
CZ284256B6 (cs)	1998-10-14	Nový způsob výroby formoterolu a příbuzných sloučenin
IE50885B1 (en)	1986-08-06	1-phenyl-2-cyclohexene-1-alkylamine derivatives,a process for their preparation and medicaments containing them
CA1109872A (fr)	1981-09-29	Derives de la purine
US4352819A (en)	1982-10-05	Novel 1-[3-(2-hydroxy-3-alkylaminopropoxy)-2-thienyl]-3-phenyl-1-propanones and their salts and a process for the preparation thereof
US4232155A (en)	1980-11-04	Purine compounds
EP0041757B1 (fr)	1984-11-07	Dérivés d'éthylène-diamine, leur préparation, compositions pharmaceutiques les contenant et produits intermédiaires pour leur préparation
JPS6121621B2 (fr)	1986-05-28
FI61868C (fi)	1982-10-11	Foerfarande foer framstaellning av terapeutiskt anvaendbara 2-enylbicyklooktan- och oktenderivat
GB2123410A (en)	1984-02-01	New derivatives of 1,2,3,4-tetrahydronaphthalene, process for their preparation and associated pharmaceutical compositions
Archer et al.	1980	4-[(Aminoalkyl) amino]-1, 2-dimethoxynaphthalenes as antimalarial agents
Scammells et al.	1996	The synthesis of the novel adenosine agonists, exo-and endo-N6-(5, 6-epoxynorborn-2-yl) adenosine
CA1281322C (fr)	1991-03-12	Pyrimidoindoles substitues
US3947584A (en)	1976-03-30	Novel indolyl alkyl amines, method of producing same, and their use as anorectic agents
IE48217B1 (en)	1984-10-31	Novel purine derivatives
FI68235B (fi)	1985-04-30	Foerfarande foer framstaellning av terapeutiskt anvaendbara 2-loradeninderivat
US4647674A (en)	1987-03-03	Bis-(dibenzo[b,d]pyranyloxy) propanes
CA1050543A (fr)	1979-03-13	Acylamino-2 benzylamines
US4269839A (en)	1981-05-26	Alkylthio-adenines used as bronchodilators
US3949091A (en)	1976-04-06	8-Substituted dibenzobicyclo[3.2.1]octadienes for treating depression