CA1104569A - Transient pro-drug forms of xanthine derivatives - Google Patents

Transient pro-drug forms of xanthine derivatives

Info

Publication number: CA1104569A
Authority: CA; Canada
Prior art keywords: theophylline; alkyl; group; straight; member selected
Prior art date: 1976-02-06
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

CA271,192A

Other languages

English (en)

French (fr)

Inventor

Kenneth B. Sloan

Nicholas S. Bodor

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.)

Interx Research Corp

Original Assignee

Interx Research Corp

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.)

1976-02-06

Filing date

1977-02-07

Publication date

1981-07-07

1977-02-07 Application filed by Interx Research Corp filed Critical Interx Research Corp

1981-07-07 Application granted granted Critical

1981-07-07 Publication of CA1104569A publication Critical patent/CA1104569A/en

Status Expired legal-status Critical Current

Links

LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title claims abstract description 34
229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title claims abstract description 4
229940002612 prodrug Drugs 0.000 title abstract description 8
239000000651 prodrug Substances 0.000 title abstract description 8
230000001052 transient effect Effects 0.000 title abstract description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 275
150000001875 compounds Chemical class 0.000 claims abstract description 48
-1 2-isobutenyl Chemical group 0.000 claims abstract description 34
125000000217 alkyl group Chemical group 0.000 claims abstract description 19
229910052794 bromium Inorganic materials 0.000 claims abstract description 18
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 18
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 15
229910052801 chlorine Inorganic materials 0.000 claims abstract description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
239000002253 acid Substances 0.000 claims abstract description 8
230000007062 hydrolysis Effects 0.000 claims abstract description 7
238000006460 hydrolysis reaction Methods 0.000 claims abstract description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 7
125000006310 cycloalkyl amino group Chemical group 0.000 claims abstract description 6
150000001413 amino acids Chemical class 0.000 claims abstract description 5
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims abstract description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 4
HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 claims abstract description 4
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 4
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 abstract description 4
229910052736 halogen Inorganic materials 0.000 claims abstract description 4
150000002367 halogens Chemical class 0.000 claims abstract description 4
238000007327 hydrogenolysis reaction Methods 0.000 claims abstract description 4
125000002883 imidazolyl group Chemical group 0.000 claims abstract description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims abstract description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims abstract description 4
125000001424 substituent group Chemical group 0.000 claims abstract description 4
125000003944 tolyl group Chemical group 0.000 claims abstract description 4
ROWMQJJMCWDJDT-UHFFFAOYSA-N tribromomethane Chemical compound Br[C](Br)Br ROWMQJJMCWDJDT-UHFFFAOYSA-N 0.000 claims abstract description 4
125000005023 xylyl group Chemical group 0.000 claims abstract description 4
125000003837 (C1-C20) alkyl group Chemical group 0.000 claims abstract 9
125000006527 (C1-C5) alkyl group Chemical group 0.000 claims abstract 4
KTOQRRDVVIDEAA-UHFFFAOYSA-N 2-methylpropane Chemical compound [CH2]C(C)C KTOQRRDVVIDEAA-UHFFFAOYSA-N 0.000 claims abstract 3
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims abstract 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract 3
229960000278 theophylline Drugs 0.000 claims description 122
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 claims description 85
238000000034 method Methods 0.000 claims description 49
238000006243 chemical reaction Methods 0.000 claims description 25
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 14
239000002904 solvent Substances 0.000 claims description 14
229940075420 xanthine Drugs 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 11
239000003960 organic solvent Substances 0.000 claims description 8
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 8
QAPJAMJGLYYNHX-UHFFFAOYSA-N 7-(hydroxymethyl)-1,3-dimethylpurine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CO)C=N2 QAPJAMJGLYYNHX-UHFFFAOYSA-N 0.000 claims description 5
150000008282 halocarbons Chemical class 0.000 claims description 5
150000007530 organic bases Chemical class 0.000 claims description 5
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 4
FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 claims description 4
238000009835 boiling Methods 0.000 claims description 4
239000003054 catalyst Substances 0.000 claims description 4
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 4
229910052708 sodium Inorganic materials 0.000 claims description 4
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 3
239000012024 dehydrating agents‎ Substances 0.000 claims description 3
229930040373 Paraformaldehyde Natural products 0.000 claims description 2
FCYRSDMGOLYDHL-UHFFFAOYSA-N chloromethoxyethane Chemical compound CCOCCl FCYRSDMGOLYDHL-UHFFFAOYSA-N 0.000 claims description 2
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 claims description 2
108700003601 dimethylglycine Proteins 0.000 claims description 2
YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 claims description 2
229940078490 n,n-dimethylglycine Drugs 0.000 claims description 2
229920002866 paraformaldehyde Polymers 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
KBXVCUKTDOSDRY-BXDIUNCMSA-N (z)-4-[(3s)-1-benzyl-3-[(4-chlorophenyl)methyl]piperidin-1-ium-3-yl]-1-hydroxy-1,4-dioxobut-2-en-2-olate Chemical compound C([C@]1(C(=O)/C=C(\O)C(=O)O)CN(CC=2C=CC=CC=2)CCC1)C1=CC=C(Cl)C=C1 KBXVCUKTDOSDRY-BXDIUNCMSA-N 0.000 claims 2
125000004663 dialkyl amino group Chemical group 0.000 claims 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical compound Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 claims 2
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 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 claims 1
239000011591 potassium Substances 0.000 claims 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
239000011734 sodium Substances 0.000 claims 1
150000003475 thallium Chemical class 0.000 claims 1
229910052740 iodine Inorganic materials 0.000 abstract description 17
241001465754 Metazoa Species 0.000 abstract description 7
201000004681 Psoriasis Diseases 0.000 abstract description 7
125000002485 formyl group Chemical group [H]C(*)=O 0.000 abstract description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 abstract description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 abstract description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 abstract description 4
CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 abstract description 2
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 abstract description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract description 2
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 abstract description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 abstract description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
229920001577 copolymer Chemical group 0.000 description 17
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
239000000047 product Substances 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
238000005192 partition Methods 0.000 description 8
239000000725 suspension Substances 0.000 description 8
150000003839 salts Chemical class 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
235000001014 amino acid Nutrition 0.000 description 5
229940024606 amino acid Drugs 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000000243 solution Substances 0.000 description 5
229940086542 triethylamine Drugs 0.000 description 5
RDSUFEJPLMOUOL-UHFFFAOYSA-N 1-(2-methylpropyl)-3,7-dihydropurine-2,6-dione Chemical compound O=C1N(CC(C)C)C(=O)NC2=C1NC=N2 RDSUFEJPLMOUOL-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 4
IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 4
239000013078 crystal Substances 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
229940095074 cyclic amp Drugs 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
150000002632 lipids Chemical class 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
230000000699 topical effect Effects 0.000 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 3
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
MUTOERQVXAXVTM-UHFFFAOYSA-N 3-(2-methylpropyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CC(C)C)C2=C1NC=N2 MUTOERQVXAXVTM-UHFFFAOYSA-N 0.000 description 2
TVZXSTTUKANBFF-UHFFFAOYSA-N 8-butyl-3,7-dihydropurine-2,6-dione Chemical compound N1C(=O)NC(=O)C2=C1N=C(CCCC)N2 TVZXSTTUKANBFF-UHFFFAOYSA-N 0.000 description 2
YKIMQEIBFMDNPV-UHFFFAOYSA-N 8-methyl-3-(2-methylpropyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CC(C)C)C2=C1NC(C)=N2 YKIMQEIBFMDNPV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
230000002682 anti-psoriatic effect Effects 0.000 description 2
239000012876 carrier material Substances 0.000 description 2
230000032823 cell division Effects 0.000 description 2
229960004132 diethyl ether Drugs 0.000 description 2
230000002500 effect on skin Effects 0.000 description 2
238000004508 fractional distillation Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
239000000203 mixture Substances 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
CMYLHRKPZBKRDX-NMONHEEDSA-N (2s)-2-amino-3-hydroxypropanoic acid;(2s,4r)-4-hydroxypyrrolidine-2-carboxylic acid;(2s)-pyrrolidine-2-carboxylic acid Chemical compound OC[C@H](N)C(O)=O.OC(=O)[C@@H]1CCCN1.O[C@H]1CN[C@H](C(O)=O)C1 CMYLHRKPZBKRDX-NMONHEEDSA-N 0.000 description 1
YROQVXMHBLVYII-UHFFFAOYSA-N 1-methyl-3-(2-methylpropyl)-7-[phenyl(phenylmethoxy)methyl]purine-2,6-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2N=CN1C(C=1C=CC=CC=1)OCC1=CC=CC=C1 YROQVXMHBLVYII-UHFFFAOYSA-N 0.000 description 1
KCNGVLNOOCLYJB-UHFFFAOYSA-N 1-methyl-7-[(4-methylphenoxy)methyl]-3-(2-methylpropyl)purine-2,6-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2N=CN1COC1=CC=C(C)C=C1 KCNGVLNOOCLYJB-UHFFFAOYSA-N 0.000 description 1
WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical group [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
HDAJPRTWESXWDW-UHFFFAOYSA-N 7-(butoxymethyl)-1-methyl-3-(2-methylpropyl)purine-2,6-dione Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1N=CN2COCCCC HDAJPRTWESXWDW-UHFFFAOYSA-N 0.000 description 1
ZBJJWIAROZKYKT-UHFFFAOYSA-N 7-(ethoxymethyl)-1-methyl-3-(2-methylpropyl)purine-2,6-dione Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1N=CN2COCC ZBJJWIAROZKYKT-UHFFFAOYSA-N 0.000 description 1
POWQPWKRHNLFIJ-UHFFFAOYSA-N 7-[2-(dimethylamino)ethoxymethyl]-1-methyl-3-(2-methylpropyl)purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N(COCCN(C)C)C=N2 POWQPWKRHNLFIJ-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
101100005986 Caenorhabditis elegans cth-2 gene Proteins 0.000 description 1
101000654316 Centruroides limpidus Beta-toxin Cll2 Proteins 0.000 description 1
UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000371 Esterases Proteins 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
229910020656 PBr5 Inorganic materials 0.000 description 1
206010065874 Psoriatic conditions Diseases 0.000 description 1
ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
CXQIJROCJUAQAQ-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl 2,2,2-trichloroethyl carbonate Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N(COC(=O)OCC(Cl)(Cl)Cl)C=N2 CXQIJROCJUAQAQ-UHFFFAOYSA-N 0.000 description 1
FDFDJMKOMDRTPE-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl 2,2-dimethylpropanoate Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N(COC(=O)C(C)(C)C)C=N2 FDFDJMKOMDRTPE-UHFFFAOYSA-N 0.000 description 1
ZPIGWRFHKDOYQT-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl 2-aminoacetate Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N(COC(=O)CN)C=N2 ZPIGWRFHKDOYQT-UHFFFAOYSA-N 0.000 description 1
ARWDAOCHNUHZKB-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl 3-phenylprop-2-enoate Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2N=CN1COC(=O)C=CC1=CC=CC=C1 ARWDAOCHNUHZKB-UHFFFAOYSA-N 0.000 description 1
YBPHOLXMLQYMGK-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl butanoate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1N=CN2COC(=O)CCC YBPHOLXMLQYMGK-UHFFFAOYSA-N 0.000 description 1
OYDCVMORMQTWQI-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl heptanoate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1N=CN2COC(=O)CCCCCC OYDCVMORMQTWQI-UHFFFAOYSA-N 0.000 description 1
LOLIJIXTBNAORP-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl octanoate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1N=CN2COC(=O)CCCCCCC LOLIJIXTBNAORP-UHFFFAOYSA-N 0.000 description 1
QIKYOEWZAGMRJN-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl propanoate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1N=CN2COC(=O)CC QIKYOEWZAGMRJN-UHFFFAOYSA-N 0.000 description 1
OVGMBUSVACSSTO-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl pyridine-2-carboxylate Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2N=CN1COC(=O)C1=CC=CC=N1 OVGMBUSVACSSTO-UHFFFAOYSA-N 0.000 description 1
BWKBHVPUGCSNRD-UHFFFAOYSA-N [1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]methyl pyridine-3-carboxylate Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2N=CN1COC(=O)C1=CC=CN=C1 BWKBHVPUGCSNRD-UHFFFAOYSA-N 0.000 description 1
OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
KFTHVTBBNUJKLV-UHFFFAOYSA-N [[1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]-phenylmethyl] hexanoate Chemical compound C1=NC=2N(CC(C)C)C(=O)N(C)C(=O)C=2N1C(OC(=O)CCCCC)C1=CC=CC=C1 KFTHVTBBNUJKLV-UHFFFAOYSA-N 0.000 description 1
SSGGDHJSBQJELB-UHFFFAOYSA-N [[1-methyl-3-(2-methylpropyl)-2,6-dioxopurin-7-yl]-phenylmethyl] octanoate Chemical compound C1=NC=2N(CC(C)C)C(=O)N(C)C(=O)C=2N1C(OC(=O)CCCCCCC)C1=CC=CC=C1 SSGGDHJSBQJELB-UHFFFAOYSA-N 0.000 description 1
230000009102 absorption Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
LNQVTSROQXJCDD-UHFFFAOYSA-N adenosine monophosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)C(OP(O)(O)=O)C1O LNQVTSROQXJCDD-UHFFFAOYSA-N 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
229960000723 ampicillin Drugs 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
235000009582 asparagine Nutrition 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
229960003067 cystine Drugs 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000036576 dermal application Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
IIJREXIVDSIOFR-UHFFFAOYSA-N dichloromethane;heptane Chemical compound ClCCl.CCCCCCC IIJREXIVDSIOFR-UHFFFAOYSA-N 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
230000003028 elevating effect Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
238000001640 fractional crystallisation 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
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
235000013773 glyceryl triacetate Nutrition 0.000 description 1
239000001087 glyceryl triacetate Substances 0.000 description 1
XXSRLPOQIVXDQV-UHFFFAOYSA-N heptane;octan-1-ol Chemical compound CCCCCCC.CCCCCCCCO XXSRLPOQIVXDQV-UHFFFAOYSA-N 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
230000008676 import Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000011968 lewis acid catalyst Substances 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
230000001185 psoriatic effect Effects 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
230000007017 scission Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000037384 skin absorption Effects 0.000 description 1
231100000274 skin absorption Toxicity 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
229960002622 triacetin Drugs 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
239000004474 valine Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA271,192A 1976-02-06 1977-02-07 Transient pro-drug forms of xanthine derivatives Expired CA1104569A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US655,786		1976-02-06
US05/655,786 US4061753A (en)	1976-02-06	1976-02-06	Treating psoriasis with transient pro-drug forms of xanthine derivatives

Publications (1)

Publication Number	Publication Date
CA1104569A true CA1104569A (en)	1981-07-07

Family

ID=24630341

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA271,192A Expired CA1104569A (en)	1976-02-06	1977-02-07	Transient pro-drug forms of xanthine derivatives

Country Status (11)

Country	Link
US (1)	US4061753A (2)
AU (1)	AU506717B2 (2)
BE (1)	BE851078A (2)
CA (1)	CA1104569A (2)
DE (1)	DE2705025A1 (2)
FR (1)	FR2340318A1 (2)
GB (1)	GB1576351A (2)
IL (1)	IL51367A0 (2)
IN (1)	IN146058B (2)
SE (1)	SE7700971L (2)
ZA (1)	ZA77621B (2)

Families Citing this family (56)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4275064A (en) *	1976-02-06	1981-06-23	Interx Research Corporation	Transient pro-drug forms of xanthine derivatives and their use as topical anti-inflammatory agents
US4133893A (en) *	1977-05-26	1979-01-09	Calbiochem Behring Corp.	Topical treatment of skin diseases
SE416810C (sv) *	1977-10-14	1982-07-19	Draco Ab	Forfarande for framstellning av xantinderivat med antiallergisk aktivitet
DE2922159A1 (de) *	1979-05-31	1980-12-04	Boehringer Mannheim Gmbh	Neue xanthin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DK172081A (da) *	1980-04-21	1981-10-22	Merck & Co Inc	Mercaptoforbindelse og fremgangsmaade til fremstilling deraf
US4341783A (en) *	1980-07-31	1982-07-27	Lemmon Company	Topical use of dyphylline and dyphylline containing compositions
GB8501488D0 (en) *	1985-01-21	1985-02-20	Beecham Group Plc	Treatment
IT1184139B (it) *	1985-01-23	1987-10-22	Proter Spa	Composti ad attivita' mucolitica e broncodilatatrice,procedimento per la loro preparazione e composizioni farmaceutiche che licontengono come principi attivi
US4923872A (en) *	1986-08-26	1990-05-08	Warner-Lambert Co.	Analogues of pyrrolo[3,2d]pyrimidin-4-ones
US4988702A (en) *	1986-08-26	1991-01-29	Warner-Lambert Company	Novel 9-deazaguanines
US4921858A (en) *	1986-10-24	1990-05-01	Warner-Lambert Company	7-deazaguanines as immunomodulators
GB8826595D0 (en) *	1988-11-14	1988-12-21	Beecham Wuelfing Gmbh & Co Kg	Active compounds
US5321029A (en) *	1988-11-14	1994-06-14	Beecham-Wuelfing Gmbh & Co.K.G.	Xanthines
US5886162A (en) *	1989-11-03	1999-03-23	Research Foundation Of State University Of New York	Lipophilic diakylaminomethylene prodrug derivatives for the inhibition of replication of viruses
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
DE4019892A1 (de) *	1990-06-22	1992-01-02	Boehringer Ingelheim Kg	Neue xanthinderivate
US5336769A (en) *	1992-02-17	1994-08-09	Kyowa Hakko Kogyo Co., Ltd.	Xanthine derivatives
US5817662A (en) *	1992-11-09	1998-10-06	Cell Therapeutics, Inc.	Substituted amino alkyl compounds
US5340813A (en) *	1992-11-09	1994-08-23	Cell Therapeutics, Inc.	Substituted aminoalkyl xanthine compounds
US6103730A (en) *	1994-03-24	2000-08-15	Cell Therapeutics, Inc.	Amine substituted compounds
US5807861A (en) *	1994-03-24	1998-09-15	Cell Therapeutics, Inc.	Amine substituted xanthinyl compounds
US5801182A (en) *	1994-03-24	1998-09-01	Cell Therapeutics, Inc.	Amine substituted compounds
DE19535504A1 (de) *	1995-09-25	1997-03-27	Bayer Ag	Substituierte Xanthine
US6541517B1 (en) *	1999-09-03	2003-04-01	Donald M. Murphy	Treatment of skin disorders
US6117904A (en) *	1999-09-03	2000-09-12	Murphy; Donald M.	Treatment of pruritus
KR100926247B1 (ko) *	2001-02-24	2009-11-12	베링거 잉겔하임 파르마 게엠베하 운트 코 카게	크산틴 유도체를 포함하는 약제학적 조성물 및 이의제조방법
RU2196583C1 (ru) *	2001-05-29	2003-01-20	Барбинов Вячеслав Викторович	Средство для наружной терапии псориаза и способ его изготовления
EP1532149B9 (de) *	2002-08-21	2011-04-20	Boehringer Ingelheim Pharma GmbH & Co. KG	8-[3-amino-piperidin-1-yl] -xanthine, deren herstellung und deren verwendung als arzneimittel
US7407955B2 (en)	2002-08-21	2008-08-05	Boehringer Ingelheim Pharma Gmbh & Co., Kg	8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US7501426B2 (en) *	2004-02-18	2009-03-10	Boehringer Ingelheim International Gmbh	8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
DE102004054054A1 (de)	2004-11-05	2006-05-11	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine
DE102005035891A1 (de) *	2005-07-30	2007-02-08	Boehringer Ingelheim Pharma Gmbh & Co. Kg	8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
EP1852108A1 (en)	2006-05-04	2007-11-07	Boehringer Ingelheim Pharma GmbH & Co.KG	DPP IV inhibitor formulations
PE20110235A1 (es)	2006-05-04	2011-04-14	Boehringer Ingelheim Int	Combinaciones farmaceuticas que comprenden linagliptina y metmorfina
KR101452915B1 (ko)	2006-05-04	2014-10-21	베링거 인겔하임 인터내셔날 게엠베하	다형태
BRPI0815405A2 (pt) *	2007-08-17	2015-02-03	Boehringer Ingelheim Int	Compostos derivados de purina, processo para a preparação de uma composição farmacêutica e uso dos mesmos
PE20091730A1 (es)	2008-04-03	2009-12-10	Boehringer Ingelheim Int	Formulaciones que comprenden un inhibidor de dpp4
PE20100156A1 (es) *	2008-06-03	2010-02-23	Boehringer Ingelheim Int	Tratamiento de nafld
KR20190016601A (ko)	2008-08-06	2019-02-18	베링거 인겔하임 인터내셔날 게엠베하	메트포르민 요법이 부적합한 환자에서의 당뇨병 치료
UY32030A (es)	2008-08-06	2010-03-26	Boehringer Ingelheim Int	"tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
UA119131C2 (uk) *	2008-08-15	2019-05-10	Бьорінгер Інгельхайм Інтернаціональ Гмбх	Похідні пурину для застосування при лікуванні пов'язаних із fab захворювань
CA2736421A1 (en)	2008-09-10	2010-03-18	Boehringer Ingelheim International Gmbh	Combination therapy for the treatment of diabetes and related conditions
US20200155558A1 (en)	2018-11-20	2020-05-21	Boehringer Ingelheim International Gmbh	Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
JP2012512848A (ja)	2008-12-23	2012-06-07	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	有機化合物の塩の形態
TW201036975A (en)	2009-01-07	2010-10-16	Boehringer Ingelheim Int	Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy
KR20240090632A (ko)	2009-11-27	2024-06-21	베링거 인겔하임 인터내셔날 게엠베하	리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료
CA3070513C (en)	2010-05-05	2023-01-03	Boehringer Ingelheim International Gmbh	A dpp-4 inhibitor for use in treatment of skin-alterations or necrosis
KR20130093012A (ko)	2010-06-24	2013-08-21	베링거 인겔하임 인터내셔날 게엠베하	당뇨병 요법
AR083878A1 (es)	2010-11-15	2013-03-27	Boehringer Ingelheim Int	Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento
DK2731947T3 (en)	2011-07-15	2019-04-23	Boehringer Ingelheim Int	SUBSTITUTED DIMERIC QUINAZOLINE DERIVATIVE, PREPARATION AND USE thereof IN PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF TYPE I AND TYPE II DIABETES
US9555001B2 (en)	2012-03-07	2017-01-31	Boehringer Ingelheim International Gmbh	Pharmaceutical composition and uses thereof
WO2013171167A1 (en)	2012-05-14	2013-11-21	Boehringer Ingelheim International Gmbh	A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome
WO2013171166A1 (en)	2012-05-14	2013-11-21	Boehringer Ingelheim International Gmbh	A xanthine derivative as dpp-4 inhibitor for use in the treatment of sirs and/or sepsis
WO2013174767A1 (en)	2012-05-24	2013-11-28	Boehringer Ingelheim International Gmbh	A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
EP3110449B1 (en)	2014-02-28	2023-06-28	Boehringer Ingelheim International GmbH	Medical use of a dpp-4 inhibitor
EP4233840A3 (en)	2016-06-10	2023-10-18	Boehringer Ingelheim International GmbH	Combinations of linagliptin and metformin

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR1265879A (fr) *	1960-05-23	1961-07-07		Dérivés substitués en -7 de la théophylline et leurs procédés de préparation
DE1226587B (de) *	1962-07-05	1966-10-13	Josef Klosa Dipl Chem Dr Rer N	Verfahren zur Herstellung neuer Theophyllinoaminosaeuren

1976
- 1976-02-06 US US05/655,786 patent/US4061753A/en not_active Expired - Lifetime
1977
- 1977-01-31 SE SE7700971A patent/SE7700971L/xx unknown
- 1977-02-01 IL IL61367A patent/IL51367A0/xx unknown
- 1977-02-03 ZA ZA770621A patent/ZA77621B/xx unknown
- 1977-02-04 FR FR7703242A patent/FR2340318A1/fr not_active Withdrawn
- 1977-02-04 BE BE2055646A patent/BE851078A/xx unknown
- 1977-02-04 GB GB4729/77A patent/GB1576351A/en not_active Expired
- 1977-02-07 CA CA271,192A patent/CA1104569A/en not_active Expired
- 1977-02-07 DE DE19772705025 patent/DE2705025A1/de active Pending
- 1977-02-07 AU AU22025/77A patent/AU506717B2/en not_active Expired
- 1977-08-03 IN IN1190/CAL/77A patent/IN146058B/en unknown

Also Published As

Publication number	Publication date
DE2705025A1 (de)	1977-08-11
BE851078A (fr)	1977-05-31
US4061753A (en)	1977-12-06
AU506717B2 (en)	1980-01-24
AU2202577A (en)	1978-08-17
GB1576351A (en)	1980-10-08
FR2340318A1 (fr)	1977-09-02
SE7700971L (sv)	1977-08-07
IN146058B (2)	1979-02-10
ZA77621B (en)	1977-12-28
IL51367A0 (en)	1977-04-29

Legal Events

Date	Code	Title	Description
1998-07-07	MKEX	Expiry

Publication	Publication Date	Title
CA1104569A (en)	1981-07-07	Transient pro-drug forms of xanthine derivatives
US4349552A (en)	1982-09-14	5-Fluorouracil derivatives, and their pharmaceutical compositions
NO913750D0 (no)	1991-09-24	Fremgangsmaate for fremstilling av terapeutisk aktive heterocykliske derivater.
TW200303860A (en)	2003-09-16	New compounds
US4110460A (en)	1978-08-29	2,3-Dihydro-imidazo[2,1-b]-thiazole derivatives and applications thereof
US4275064A (en)	1981-06-23	Transient pro-drug forms of xanthine derivatives and their use as topical anti-inflammatory agents
KR870001144B1 (ko)	1987-06-11	삼환 옥스인돌 카복스아미드 유도체의 제조방법
NZ188770A (en)	1984-07-31	Thiazolinylguanidine derivatives and pharmaceutical compositions
JPH07500817A (ja)	1995-01-26	有機ニトラート、その製造方法及びこれを心臓血管疾患の治療に使用する方法
JPS5681578A (en)	1981-07-03	Novel thioalkyl amide derivative
JPS58194873A (ja)	1983-11-12	１−（３，４，５−トリメトキシシンナモイル）−４−アミノカルボニルメチル置換ピペラジン誘導体
US5118703A (en)	1992-06-02	Prodrugs of antiinflammatory 3-acyl-2-oxindole-1-carboxamides
PL103682B1 (pl)	1979-07-31	Sposob wytwarzania nowych pochodnych indazoliloksy-4-propanoloaminy
US5281708A (en)	1994-01-25	9-Substituted-8-halo or -8-hydroxy-9-deazaguanines as inhibitors of PNP
US2350265A (en)	1944-05-30	Pyrimidine compounds
CA1311763C (en)	1992-12-22	Benzenesulfonamide derivatives and a process for the preparation thereof
SU1428200A3 (ru)	1988-09-30	Способ получени рацемических или оптически активных производных 9- или 11-аминоэбурнанкарбоновой кислоты или их кислотно-аддитивных солей
US4313956A (en)	1982-02-02	Novel sypathomimetic amine prodrugs
KR810000762B1 (ko)	1981-07-02	신규크산틴유도체의 제조방법
US4272529A (en)	1981-06-09	O-Alcoxycarbonylphenyl esters of anthranilic acid with therapeutical activity, method for their preparation and related pharmaceutical composition
EP0126894B1 (en)	1987-08-26	Tropone derivatives, processes for preparation thereof and pharmaceutical composition comprising the same
NO150316C (no)	1984-10-03	Analogifremgangsmaate ved fremstilling av terapeutisk aktive nitrosoureaderivater
US4602018A (en)	1986-07-22	Condensed as-triazine derivatives
US3544574A (en)	1970-12-01	Thiamine halophenylalkyl disulfides
US4139709A (en)	1979-02-13	1,2-Diphenyl-3,5-ditrifluoroacetyloxy-4-butyl-5-hydroxy-3-pyrazoline