LV10100B - Inhibitors of purine nucleoside phosphorylase - Google Patents

Inhibitors of purine nucleoside phosphorylase Download PDF

Info

Publication number: LV10100B
Authority: LV; Latvia
Prior art keywords: compound; cyclo; ethyl; substituted; amino
Prior art date: 1989-10-31

Application number

LVP-93-342A

Other languages

English (en)

Latvian (lv)

Other versions

LV10100A (lv

Inventor

Secrist John A Iii

Erion Mark David

John A Montgomery

Steven E Ealick

Wayne C Guida

Niwas Shri

Original Assignee

Biocryst Pharm Inc

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.)

1989-10-31

Filing date

1993-05-14

Publication date

1995-08-20

1989-10-31 Priority claimed from US07/429,098 external-priority patent/US4985434A/en

1989-10-31 Priority claimed from US07/429,099 external-priority patent/US5008265A/en

1989-10-31 Priority claimed from US07/429,100 external-priority patent/US4985433A/en

1989-10-31 Priority claimed from US07/429,097 external-priority patent/US5008270A/en

1993-05-14 Application filed by Biocryst Pharm Inc filed Critical Biocryst Pharm Inc

1994-05-10 Publication of LV10100A publication Critical patent/LV10100A/xx

1995-08-20 Publication of LV10100B publication Critical patent/LV10100B/en

Links

101710101148 Probable 6-oxopurine nucleoside phosphorylase Proteins 0.000 title claims description 31
102000030764 Purine-nucleoside phosphorylase Human genes 0.000 title claims description 31
239000003112 inhibitor Substances 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims description 234
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 182
-1 3-tetrahydrofuranyl Chemical group 0.000 claims description 148
238000000034 method Methods 0.000 claims description 77
238000006243 chemical reaction Methods 0.000 claims description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
125000000217 alkyl group Chemical group 0.000 claims description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 17
230000015572 biosynthetic process Effects 0.000 claims description 15
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 12
210000001744 T-lymphocyte Anatomy 0.000 claims description 12
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 12
CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 claims description 11
MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims description 10
COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 claims description 10
125000002723 alicyclic group Chemical group 0.000 claims description 9
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 8
239000005695 Ammonium acetate Substances 0.000 claims description 8
229940043376 ammonium acetate Drugs 0.000 claims description 8
235000019257 ammonium acetate Nutrition 0.000 claims description 8
235000011114 ammonium hydroxide Nutrition 0.000 claims description 8
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
229910052708 sodium Inorganic materials 0.000 claims description 8
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 7
125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
230000004727 humoral immunity Effects 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
239000004471 Glycine Substances 0.000 claims description 5
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000005842 heteroatom Chemical group 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
239000011734 sodium Substances 0.000 claims description 5
125000005750 substituted cyclic group Chemical group 0.000 claims description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
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 claims description 4
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
125000001072 heteroaryl group Chemical group 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
239000001632 sodium acetate Substances 0.000 claims description 4
235000017281 sodium acetate Nutrition 0.000 claims description 4
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 3
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 3
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 3
239000002253 acid Substances 0.000 claims description 3
150000001350 alkyl halides Chemical class 0.000 claims description 3
230000001590 oxidative effect Effects 0.000 claims description 3
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 3
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 3
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
125000005907 alkyl ester group Chemical group 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
150000004702 methyl esters Chemical class 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
RFFFKMOABOFIDF-UHFFFAOYSA-N Pentanenitrile Chemical class CCCCC#N RFFFKMOABOFIDF-UHFFFAOYSA-N 0.000 claims 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
CYYRZRISTSSCNZ-UHFFFAOYSA-N 3-(4-oxo-3,5-dihydropyrrolo[3,2-d]pyrimidin-7-yl)propanenitrile Chemical compound O=C1C2=C(N=CN1)C(=CN2)CCC#N CYYRZRISTSSCNZ-UHFFFAOYSA-N 0.000 claims 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
101100440696 Caenorhabditis elegans cor-1 gene Proteins 0.000 claims 1
238000011065 in-situ storage Methods 0.000 claims 1
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims 1
239000007800 oxidant agent Substances 0.000 claims 1
125000001425 triazolyl group Chemical group 0.000 claims 1
239000000243 solution Substances 0.000 description 148
239000000203 mixture Substances 0.000 description 71
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 60
239000000543 intermediate Substances 0.000 description 59
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 54
239000000741 silica gel Substances 0.000 description 45
229910002027 silica gel Inorganic materials 0.000 description 45
229960001866 silicon dioxide Drugs 0.000 description 45
239000007787 solid Substances 0.000 description 43
229910001868 water Inorganic materials 0.000 description 38
239000003921 oil Substances 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
230000000694 effects Effects 0.000 description 31
XQFGVGNRDPFKFJ-UHFFFAOYSA-N 1,2,3,5,6,7-hexahydropyrrolo[1,2-b]pyridazine Chemical compound N1CCC=C2CCCN21 XQFGVGNRDPFKFJ-UHFFFAOYSA-N 0.000 description 30
239000000047 product Substances 0.000 description 29
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 28
229910019142 PO4 Inorganic materials 0.000 description 27
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 27
239000010452 phosphate Substances 0.000 description 27
238000000746 purification Methods 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 23
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
239000007858 starting material Substances 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
239000000706 filtrate Substances 0.000 description 20
102000004190 Enzymes Human genes 0.000 description 19
108090000790 Enzymes Proteins 0.000 description 19
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
239000008194 pharmaceutical composition Substances 0.000 description 17
238000009835 boiling Methods 0.000 description 16
239000003480 eluent Substances 0.000 description 16
241001465754 Metazoa Species 0.000 description 15
239000006227 byproduct Substances 0.000 description 15
230000005764 inhibitory process Effects 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
238000001816 cooling Methods 0.000 description 14
150000002081 enamines Chemical class 0.000 description 14
239000007928 intraperitoneal injection Substances 0.000 description 14
238000000926 separation method Methods 0.000 description 14
229910000104 sodium hydride Inorganic materials 0.000 description 14
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
125000003545 alkoxy group Chemical group 0.000 description 13
229960003786 inosine Drugs 0.000 description 13
229910000029 sodium carbonate Inorganic materials 0.000 description 12
239000002904 solvent Substances 0.000 description 12
229930010555 Inosine Natural products 0.000 description 11
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 11
150000002825 nitriles Chemical class 0.000 description 11
229920006395 saturated elastomer Polymers 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 10
238000003756 stirring Methods 0.000 description 10
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 9
238000001914 filtration Methods 0.000 description 9
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 9
229910052736 halogen Inorganic materials 0.000 description 9
150000002367 halogens Chemical group 0.000 description 9
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 9
229940011051 isopropyl acetate Drugs 0.000 description 9
239000012299 nitrogen atmosphere Substances 0.000 description 9
238000010992 reflux Methods 0.000 description 9
229910001220 stainless steel Inorganic materials 0.000 description 9
239000010935 stainless steel Substances 0.000 description 9
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 8
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
150000001408 amides Chemical class 0.000 description 8
239000012298 atmosphere Substances 0.000 description 8
XVHFAJKXXPJYDW-UHFFFAOYSA-N pyrrolo[3,2-d]pyrimidin-4-one Chemical compound O=C1N=CN=C2C=CN=C12 XVHFAJKXXPJYDW-UHFFFAOYSA-N 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
239000012312 sodium hydride Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
229940040526 anhydrous sodium acetate Drugs 0.000 description 7
239000012043 crude product Substances 0.000 description 7
239000013078 crystal Substances 0.000 description 7
238000000605 extraction Methods 0.000 description 7
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
239000010410 layer Substances 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
229910004373 HOAc Inorganic materials 0.000 description 6
238000010828 elution Methods 0.000 description 6
235000019439 ethyl acetate Nutrition 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
230000002401 inhibitory effect Effects 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
229910000069 nitrogen hydride Inorganic materials 0.000 description 6
229910052760 oxygen Inorganic materials 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
KWGZNYCFTYOQHV-UHFFFAOYSA-N 3-pyridin-2-ylpropanenitrile Chemical compound N#CCCC1=CC=CC=N1 KWGZNYCFTYOQHV-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
239000002585 base Substances 0.000 description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
244000309466 calf Species 0.000 description 5
239000003937 drug carrier Substances 0.000 description 5
238000001035 drying Methods 0.000 description 5
238000001952 enzyme assay Methods 0.000 description 5
229940093499 ethyl acetate Drugs 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000002777 nucleoside Substances 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
150000003839 salts Chemical class 0.000 description 5
210000000952 spleen Anatomy 0.000 description 5
230000001629 suppression Effects 0.000 description 5
150000003536 tetrazoles Chemical class 0.000 description 5
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 5
150000003852 triazoles Chemical class 0.000 description 5
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
KANSEWMVEJOUAE-UHFFFAOYSA-N 3-(2-adamantyl)propanenitrile Chemical class C1C(C2)CC3CC1C(CCC#N)C2C3 KANSEWMVEJOUAE-UHFFFAOYSA-N 0.000 description 4
DFCILIYDUNACSC-UHFFFAOYSA-N 3-cyclohexylpropanenitrile Chemical compound N#CCCC1CCCCC1 DFCILIYDUNACSC-UHFFFAOYSA-N 0.000 description 4
HLLQLVYVGPYYBK-UHFFFAOYSA-N 3-pyridin-3-ylpropanenitrile Chemical compound N#CCCC1=CC=CN=C1 HLLQLVYVGPYYBK-UHFFFAOYSA-N 0.000 description 4
GCAVYPNOOWBODM-UHFFFAOYSA-N 4-[4-hydroxy-3-[(4-hydroxy-3-methoxyphenyl)methyl]-2-(hydroxymethyl)butyl]benzene-1,2-diol Chemical compound C1=C(O)C(OC)=CC(CC(CO)C(CO)CC=2C=C(O)C(O)=CC=2)=C1 GCAVYPNOOWBODM-UHFFFAOYSA-N 0.000 description 4
NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 4
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
230000006978 adaptation Effects 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
235000012538 ammonium bicarbonate Nutrition 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
125000001309 chloro group Chemical group Cl* 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
230000003292 diminished effect Effects 0.000 description 4
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
125000001153 fluoro group Chemical group F* 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
238000011694 lewis rat Methods 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
239000000463 material Substances 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
125000002560 nitrile group Chemical group 0.000 description 4
125000003835 nucleoside group Chemical group 0.000 description 4
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239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
238000004114 suspension culture Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 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
238000002054 transplantation Methods 0.000 description 1
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
125000006493 trifluoromethyl benzyl group Chemical group 0.000 description 1
BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/31—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing rings other than six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/35—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/40—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by doubly-bound oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Virology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Pyrrole Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

LVP-93-342A 1989-10-31 1993-05-14 Inhibitors of purine nucleoside phosphorylase LV10100B (en)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US07/429,098 US4985434A (en)	1989-10-31	1989-10-31	7-substituted derivatives of 2-amino-3H,5H-pyrrolo(3,2-d)pyrimidin-4-ones and pharamceutical uses and compositions containing the same
US07/429,099 US5008265A (en)	1989-10-31	1989-10-31	2-amino-7-(alicyclomethyl)-3H,5H,-pyrrolo[3,2-d]pyrimidin-4-ones and pharmaceutical uses and compositions containing the same
US07/429,100 US4985433A (en)	1989-10-31	1989-10-31	2-amino-7-(pyridinylmethyl)-3H,5H-pyrrolo[3,2-d]pyrimidin-4-ones and pharmaceutical uses and compositions containing the same
US07/429,097 US5008270A (en)	1989-10-31	1989-10-31	2-amino-7-(heterocyclomethyl)-3H,5H-pyrrolo[3,2-d]pyrimidin-4-ones and pharmaceutical uses and compositions containing the same
US44279889A	1989-11-29	1989-11-29
PCT/US1990/005756 WO1991006548A1 (fr)	1989-10-31	1990-10-12	Inhibiteurs de phosphorylase de nucleoside de purine

Publications (2)

Publication Number	Publication Date
LV10100A LV10100A (lv)	1994-05-10
LV10100B true LV10100B (en)	1995-08-20

Family

ID=27541578

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LVP-93-342A LV10100B (en)	1989-10-31	1993-05-14	Inhibitors of purine nucleoside phosphorylase

Country Status (9)

Country	Link
EP (1)	EP0500653A4 (fr)
JP (1)	JP2866478B2 (fr)
AU (1)	AU654264B2 (fr)
CA (1)	CA2072123C (fr)
FI (1)	FI103972B1 (fr)
HU (1)	HUT61765A (fr)
LV (1)	LV10100B (fr)
NO (1)	NO301423B1 (fr)
WO (1)	WO1991006548A1 (fr)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5726311A (en) *	1989-11-29	1998-03-10	Biocryst Pharmaceuticals, Inc.	7-disubstituted-methyl-4-oxo-3H,5H-pyrrolo 3,2-d!pyrimidine and pharmaceutical uses and compositions containing the same
US5236926A (en) *	1992-02-03	1993-08-17	Warner-Lambert Company	9-substituted-8-halo or -8-hydroxy-9-deazaguanines as inhibitors or PNP for pharmaceutical compositions
FI944933A7 (fi) *	1992-04-21	1994-10-20	Biocryst Pharm Inc	7-disubstitoitu metyyli-4-okso-3H,5H-pyrrolo(3,2-d) pyrimidiini ja sit ä sisältäviä farmaseuttisia käyttöjä ja koostumuksia
FI971413L (fi) *	1994-10-05	1997-04-04	Chiroscience Ltd	Puriini- ja guaniiniyhdisteet PNP:n estäjinä
GB9520364D0 (en) *	1995-10-05	1995-12-06	Chiroscience Ltd	Compouundds
GB9520363D0 (en) *	1995-10-05	1995-12-06	Chiroscience Ltd	Compounds
CN1107068C (zh) *	1997-05-29	2003-04-30	诺瓦提斯公司	2－氨基－7－(1－取代的－2－羟乙基)－3,5－二氢－吡咯并[3,2－d]嘧啶－4－酮
US6174888B1 (en)	1998-05-28	2001-01-16	Novartis Ag	2-amino-7-(1-substituted-2-hydroxyethyl)-3,5-dihydropyrrolo[3,2-D]pyrimidin-4-ones
JP4496586B2 (ja) *	2000-01-24	2010-07-07	日産化学工業株式会社	キノリルアクリロニトリルの製造法及びその中間体
EP1539783B1 (fr) *	2002-08-21	2011-04-13	Albert Einstein College Of Medicine Of Yeshiva University	Inhibiteurs des phosphorylases de nucleoside et des nucleosidases
NZ523970A (en) *	2003-02-04	2005-02-25	Ind Res Ltd	Process for preparing inhibitors of nucleoside phoshorylases and nucleosidases
CA2710039C (fr)	2007-12-26	2018-07-03	Critical Outcome Technologies, Inc.	Semicarbazones, thiosemicarnazones et composes associes, et methodes de traitement du cancer
EP2318406B1 (fr)	2008-07-17	2016-01-27	Critical Outcome Technologies, Inc.	Composés inhibiteurs et procédés de traitement du cancer
EP2552915B1 (fr)	2010-04-01	2017-07-19	Critical Outcome Technologies Inc.	Composés pour le traitement du vih

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5988484A (ja) *	1982-11-09	1984-05-22	Takeda Chem Ind Ltd	新規７−デアザプリン誘導体
IE60433B1 (en) *	1986-08-26	1994-07-13	Warner Lambert Co	Novel 9-deazaguanines
US4921858A (en) *	1986-10-24	1990-05-01	Warner-Lambert Company	7-deazaguanines as immunomodulators
CA1294960C (fr) *	1986-10-24	1992-01-28	Thomas C. Malone	7-deazaguanines en tant qu'immunomodulateurs
DE3726044A1 (de) *	1987-02-11	1988-08-25	Bayer Ag	Akarizide mittel auf basis von azomethinderivaten und azomethine des 2,3-diaminomaleinsaeurenitrils
US4927830A (en) *	1988-04-08	1990-05-22	The Regents Of The University Of Michigan	Acyclic pyrrolo[2,3-D]pyrimidine analogs as antiviral agents
RU2093513C1 (ru) *	1989-02-27	1997-10-20	Биокрайст Фармасьютикалз Инк.	Производные 9-деазагуанины или их таутомеры и фармацевтическая композиция, обладающая способностью ингибировать активность пуриннуклеозид фосфорилазы у млекопитающих
US4985433A (en) *	1989-10-31	1991-01-15	Biocryst, Inc.	2-amino-7-(pyridinylmethyl)-3H,5H-pyrrolo[3,2-d]pyrimidin-4-ones and pharmaceutical uses and compositions containing the same
US4985434A (en) *	1989-10-31	1991-01-15	Biocryst, Inc.	7-substituted derivatives of 2-amino-3H,5H-pyrrolo(3,2-d)pyrimidin-4-ones and pharamceutical uses and compositions containing the same

1990
- 1990-10-12 CA CA002072123A patent/CA2072123C/fr not_active Expired - Fee Related
- 1990-10-12 EP EP90916628A patent/EP0500653A4/en not_active Withdrawn
- 1990-10-12 JP JP2515550A patent/JP2866478B2/ja not_active Expired - Lifetime
- 1990-10-12 WO PCT/US1990/005756 patent/WO1991006548A1/fr not_active Ceased
- 1990-10-12 AU AU67125/90A patent/AU654264B2/en not_active Ceased
- 1990-10-12 HU HU9201450A patent/HUT61765A/hu unknown
1992
- 1992-04-28 FI FI921900A patent/FI103972B1/fi active
- 1992-04-29 NO NO921679A patent/NO301423B1/no not_active IP Right Cessation
1993
- 1993-05-14 LV LVP-93-342A patent/LV10100B/en unknown

Also Published As

Publication number	Publication date
NO921679D0 (no)	1992-04-29
NO301423B1 (no)	1997-10-27
JP2866478B2 (ja)	1999-03-08
FI103972B (fi)	1999-10-29
HU9201450D0 (en)	1992-09-28
FI921900A0 (fi)	1992-04-28
LV10100A (lv)	1994-05-10
CA2072123A1 (fr)	1991-05-01
FI921900L (fi)	1992-04-28
WO1991006548A1 (fr)	1991-05-16
NO921679L (no)	1992-06-17
JPH05504551A (ja)	1993-07-15
AU6712590A (en)	1991-05-31
CA2072123C (fr)	2001-06-12
HUT61765A (en)	1993-03-01
AU654264B2 (en)	1994-11-03
FI103972B1 (fi)	1999-10-29
EP0500653A1 (fr)	1992-09-02
EP0500653A4 (en)	1995-08-23

Publication	Publication Date	Title
JP4205168B2 (ja)	2009-01-07	ピリミジン誘導体およびその製造法
LV10100B (en)	1995-08-20	Inhibitors of purine nucleoside phosphorylase
Bhuyan et al.	1990	Studies on uracils. 10. A facile one-pot synthesis of pyrido [2, 3-d]-and pyrazolo [3, 4-d] pyrimidines
EP0647227B1 (fr)	1996-10-09	Purinones utilises comme antiangineux
US5008270A (en)	1991-04-16	2-amino-7-(heterocyclomethyl)-3H,5H-pyrrolo[3,2-d]pyrimidin-4-ones and pharmaceutical uses and compositions containing the same
WO2001034605A1 (fr)	2001-05-17	2-ARYL-3-(HETEROARYL)-IMIDAZO[1,2-a]PYRIMIDINES SUBSTITUEES, ET COMPOSITIONS PHARMACEUTIQUES ET PROCEDES ASSOCIES
CZ277698B6 (en)	1993-03-17	Racemic or optically active bis-aza-bicyclic compounds, process for preparing thereof, intermediates and use thereof
SK76699A3 (en)	2000-05-16	Pyrrolo[3,4-d]pyrimidinone derivatives and their use as medicaments
US5565463A (en)	1996-10-15	9-subtituted-8-unsubstituted-9-deazaguanines
US5008265A (en)	1991-04-16	2-amino-7-(alicyclomethyl)-3H,5H,-pyrrolo[3,2-d]pyrimidin-4-ones and pharmaceutical uses and compositions containing the same
US4985433A (en)	1991-01-15	2-amino-7-(pyridinylmethyl)-3H,5H-pyrrolo[3,2-d]pyrimidin-4-ones and pharmaceutical uses and compositions containing the same
US5189039A (en)	1993-02-23	7-disubstituted-methyl-4-oxo-3H,5H-pyrrolo[3,2d]pyrimidine and pharmaceutical uses and compositions containing the same
AU4276693A (en)	1993-11-18	7-disubstituted-methyl-4-oxo-3H,5H-pyrrolo(3,2-d)pyrim idine and pharmaceutical uses and compositions containing the same
DE602004012146T2 (de)	2009-03-19	Pyrazolopyrimidine
EP1023291B1 (fr)	2004-05-26	Derives de dipyrido-imidazole utiles pour le traitement de troubles du systeme nerveux central
DE2133998A1 (de)	1973-01-25	2,3-dihydro-oxo-imidazo eckige klammer auf 1,2-a eckige klammer zu -pyrimidine, deren saeureadditionssalze und verfahren zu deren herstellung
RU2097384C1 (ru)	1997-11-27	Производные 2-амино-7-(chr2r3)-3н,5н-пирроло[3,2-d]-пиримидин-4-она, способы их получения и способ селективного ингибирования пролиферации т-лимфоцитов млекопитающего и не оказывающий воздействия на b-лимфоциты
US5726311A (en)	1998-03-10	7-disubstituted-methyl-4-oxo-3H,5H-pyrrolo 3,2-d!pyrimidine and pharmaceutical uses and compositions containing the same
Su et al.	1984	Pyrimidines. 21. Novel reactions of 5‐cyano‐1, 3‐dimethyluracil with carbon nucleophiles. A facile preparation of certain pyrido [2, 3‐d] pyrimidines
US4129653A (en)	1978-12-12	Substituted pyrrolo [1,2-c] quinazolines and pharmaceutical compositions and methods employing them
DE60130772T2 (de)	2008-07-17	Pyrrolotriazolopyrimidinonderivate
Birnberg et al.	1995	The synthesis of 5‐arylpyrrolo [3, 2‐b] pyridines and 7‐arylpyrrolo [3, 2‐b] pyridines: Addition of 3‐aminopyrroles to aryl enaminones
US20040254181A1 (en)	2004-12-16	Process for the preparation of 9-deazaguanine derivatives
RU2191175C2 (ru)	2002-10-20	Конденсированные изоиндолоны в качестве ингибиторов протеинкиназы с
EP0970029A1 (fr)	2000-01-12	Procede de preparation de derives 9-desazaguanine