SK17332002A3 - Purínové deriváty - Google Patents

Purínové deriváty Download PDF

Info

Publication number: SK17332002A3
Authority: SK; Slovakia
Prior art keywords: amino; formula; ethyl; alkyl; compound
Prior art date: 2000-06-27

Application number

SK1733-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Simon John Mantell

Sandra Marina Monaghan

Peter Thomas Stephenson

Original Assignee

Pfizer 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.)

2000-06-27

Filing date

2001-06-14

Publication date

2004-03-02

2001-06-14 Application filed by Pfizer Inc. filed Critical Pfizer Inc.

2004-03-02 Publication of SK17332002A3 publication Critical patent/SK17332002A3/sk

Links

229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 3
125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 492
238000000034 method Methods 0.000 claims abstract description 218
239000000203 mixture Substances 0.000 claims abstract description 116
150000003839 salts Chemical class 0.000 claims abstract description 79
239000012453 solvate Substances 0.000 claims abstract description 59
238000002360 preparation method Methods 0.000 claims abstract description 35
230000008569 process Effects 0.000 claims abstract description 15
-1 azetidinyl- Chemical group 0.000 claims description 132
125000006239 protecting group Chemical group 0.000 claims description 103
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 81
229910052739 hydrogen Inorganic materials 0.000 claims description 53
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
239000001257 hydrogen Substances 0.000 claims description 45
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 41
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
125000000217 alkyl group Chemical group 0.000 claims description 33
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 28
229910052799 carbon Inorganic materials 0.000 claims description 26
238000010511 deprotection reaction Methods 0.000 claims description 25
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 23
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 22
229910052757 nitrogen Inorganic materials 0.000 claims description 22
201000004624 Dermatitis Diseases 0.000 claims description 21
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 20
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 19
150000002367 halogens Chemical class 0.000 claims description 19
125000004093 cyano group Chemical group *C#N 0.000 claims description 18
125000001624 naphthyl group Chemical group 0.000 claims description 18
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 17
125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
241000124008 Mammalia Species 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
150000002431 hydrogen Chemical class 0.000 claims description 15
238000011282 treatment Methods 0.000 claims description 15
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 14
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 13
208000007882 Gastritis Diseases 0.000 claims description 12
206010006451 bronchitis Diseases 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
201000010099 disease Diseases 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 10
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
101150051188 Adora2a gene Proteins 0.000 claims description 9
241000590002 Helicobacter pylori Species 0.000 claims description 9
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 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 9
229940037467 helicobacter pylori Drugs 0.000 claims description 9
229940044601 receptor agonist Drugs 0.000 claims description 9
239000000018 receptor agonist Substances 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
208000006673 asthma Diseases 0.000 claims description 8
208000010668 atopic eczema Diseases 0.000 claims description 8
239000000460 chlorine Substances 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
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000002947 alkylene group Chemical group 0.000 claims description 7
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 6
201000006474 Brain Ischemia Diseases 0.000 claims description 6
206010006458 Bronchitis chronic Diseases 0.000 claims description 6
206010008120 Cerebral ischaemia Diseases 0.000 claims description 6
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
206010009137 Chronic sinusitis Diseases 0.000 claims description 6
206010009900 Colitis ulcerative Diseases 0.000 claims description 6
208000011231 Crohn disease Diseases 0.000 claims description 6
201000003883 Cystic fibrosis Diseases 0.000 claims description 6
206010014561 Emphysema Diseases 0.000 claims description 6
208000010228 Erectile Dysfunction Diseases 0.000 claims description 6
206010020772 Hypertension Diseases 0.000 claims description 6
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
208000028017 Psychotic disease Diseases 0.000 claims description 6
206010040070 Septic Shock Diseases 0.000 claims description 6
208000006011 Stroke Diseases 0.000 claims description 6
201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 6
206010008118 cerebral infarction Diseases 0.000 claims description 6
208000007451 chronic bronchitis Diseases 0.000 claims description 6
208000027157 chronic rhinosinusitis Diseases 0.000 claims description 6
230000006378 damage Effects 0.000 claims description 6
206010012601 diabetes mellitus Diseases 0.000 claims description 6
206010015037 epilepsy Diseases 0.000 claims description 6
201000001881 impotence Diseases 0.000 claims description 6
229910052740 iodine Inorganic materials 0.000 claims description 6
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
230000002093 peripheral effect Effects 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
206010039083 rhinitis Diseases 0.000 claims description 6
230000036303 septic shock Effects 0.000 claims description 6
208000019553 vascular disease Diseases 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
208000007984 Female Infertility Diseases 0.000 claims description 5
206010021928 Infertility female Diseases 0.000 claims description 5
201000004681 Psoriasis Diseases 0.000 claims description 5
206010063837 Reperfusion injury Diseases 0.000 claims description 5
229940121363 anti-inflammatory agent Drugs 0.000 claims description 5
239000002260 anti-inflammatory agent Substances 0.000 claims description 5
201000009267 bronchiectasis Diseases 0.000 claims description 5
239000004202 carbamide Substances 0.000 claims description 5
229910002091 carbon monoxide Inorganic materials 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
201000009151 chronic rhinitis Diseases 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
210000001035 gastrointestinal tract Anatomy 0.000 claims description 5
125000001475 halogen functional group Chemical group 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
208000023504 respiratory system disease Diseases 0.000 claims description 5
206010012434 Dermatitis allergic Diseases 0.000 claims description 4
208000007466 Male Infertility Diseases 0.000 claims description 4
125000002393 azetidinyl group Chemical group 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 4
230000029663 wound healing Effects 0.000 claims description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])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
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
201000006417 multiple sclerosis Diseases 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
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 3
125000004263 tetrahydroisoquinolin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])C2=C([H])C([H])=C([H])C([H])=C2C1([H])* 0.000 claims description 3
QICYZVIFORTWAI-KCIBBDPESA-N (2s,3s,4r,5r)-5-[2-[(cyclohexylcarbamoylamino)methyl]-6-(2,2-diphenylethylamino)purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(CNC(=O)NC3CCCCC3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 QICYZVIFORTWAI-KCIBBDPESA-N 0.000 claims description 2
JZTVQVQEFVILIO-XYIJYTLJSA-N (2s,3s,4r,5r)-5-[6-(2,2-diphenylethylamino)-2-[[2-[di(propan-2-yl)amino]ethylcarbamoylamino]methyl]purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(CNC(=O)NCCN(C(C)C)C(C)C)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 JZTVQVQEFVILIO-XYIJYTLJSA-N 0.000 claims description 2
FTPHJZMQCAHRAF-FTBITJBVSA-N 1-[[6-[2,2-bis(3-chlorophenyl)ethylamino]-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]methyl]-3-[2-[di(propan-2-yl)amino]ethyl]urea Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=NC(CNC(=O)NCCN(C(C)C)C(C)C)=NC=1NCC(C=1C=C(Cl)C=CC=1)C1=CC=CC(Cl)=C1 FTPHJZMQCAHRAF-FTBITJBVSA-N 0.000 claims description 2
YPGIEXZBQFFQRA-FTBITJBVSA-N 1-[[6-[2,2-bis(4-chlorophenyl)ethylamino]-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]methyl]-3-[2-[di(propan-2-yl)amino]ethyl]urea Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=NC(CNC(=O)NCCN(C(C)C)C(C)C)=NC=1NCC(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 YPGIEXZBQFFQRA-FTBITJBVSA-N 0.000 claims description 2
241000589989 Helicobacter Species 0.000 claims description 2
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
230000002496 gastric effect Effects 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
208000027866 inflammatory disease Diseases 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
201000008937 atopic dermatitis Diseases 0.000 claims 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
MFKOLMGPXLGNHC-LVLBQQNZSA-N (2s,3s,4r,5r)-5-[2-[[(1-benzylpiperidin-4-yl)carbamoylamino]methyl]-6-(2,2-diphenylethylamino)purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(CNC(=O)NC3CCN(CC=4C=CC=CC=4)CC3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 MFKOLMGPXLGNHC-LVLBQQNZSA-N 0.000 claims 1
UJZHSZLVUAJTBC-DEGFIOCKSA-N (2s,3s,4r,5r)-5-[2-[[2-(dibutylamino)ethylcarbamoylamino]methyl]-6-(2,2-diphenylethylamino)purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@H](O3)C(=O)NCC)O)C2=NC(CNC(=O)NCCN(CCCC)CCCC)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 UJZHSZLVUAJTBC-DEGFIOCKSA-N 0.000 claims 1
UXAQXHMBWCHLNB-VIBCZQBBSA-N (2s,3s,4r,5r)-5-[2-[[2-[benzenesulfonyl(propan-2-yl)amino]ethylcarbamoylamino]methyl]-6-(2,2-diphenylethylamino)purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(CNC(=O)NCCN(C(C)C)S(=O)(=O)C=3C=CC=CC=3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 UXAQXHMBWCHLNB-VIBCZQBBSA-N 0.000 claims 1
TXXBHXAZPFWXLD-ORUSXYGBSA-N (2s,3s,4r,5r)-5-[2-[[2-[benzoyl(propan-2-yl)amino]ethylcarbamoylamino]methyl]-6-(2,2-diphenylethylamino)purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(CNC(=O)NCCN(C(C)C)C(=O)C=3C=CC=CC=3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 TXXBHXAZPFWXLD-ORUSXYGBSA-N 0.000 claims 1
UUSCHBHDAQZLNA-CKXMCULTSA-N (2s,3s,4r,5r)-5-[2-[[2-[di(propan-2-yl)amino]ethylcarbamoylamino]methyl]-6-(naphthalen-1-ylmethylamino)purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(CNC(=O)NCCN(C(C)C)C(C)C)=NC(NCC=3C4=CC=CC=C4C=CC=3)=C2N=C1 UUSCHBHDAQZLNA-CKXMCULTSA-N 0.000 claims 1
IDKURHCOVIGVGH-DEGFIOCKSA-N (2s,3s,4r,5r)-5-[6-(2,2-diphenylethylamino)-2-[[(1-pyridin-2-ylpiperidin-4-yl)carbamoylamino]methyl]purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(CNC(=O)NC3CCN(CC3)C=3N=CC=CC=3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 IDKURHCOVIGVGH-DEGFIOCKSA-N 0.000 claims 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
YNQOLUQTSOXODE-BBKOCAQVSA-N 1-[(1-benzylpiperidin-4-yl)methyl]-3-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purin-2-yl]methyl]urea Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(CNC(=O)NCC3CCN(CC=4C=CC=CC=4)CC3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 YNQOLUQTSOXODE-BBKOCAQVSA-N 0.000 claims 1
ARQKKSJPRBAUHE-JRFMUSTFSA-N 1-[2-(3,4-dihydro-1h-isoquinolin-2-yl)ethyl]-3-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purin-2-yl]methyl]urea Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(CNC(=O)NCCN3CC4=CC=CC=C4CC3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 ARQKKSJPRBAUHE-JRFMUSTFSA-N 0.000 claims 1
CGZUKSBTNRXYHV-KKKGQUFWSA-N 1-[2-(dicyclopentylamino)ethyl]-3-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purin-2-yl]methyl]urea Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(CNC(=O)NCCN(C3CCCC3)C3CCCC3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 CGZUKSBTNRXYHV-KKKGQUFWSA-N 0.000 claims 1
XKTUCVHQBLNEGR-JRFMUSTFSA-N 1-[2-[tert-butyl(cyclohexyl)amino]ethyl]-3-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purin-2-yl]methyl]urea Chemical compound C1CCCCC1N(C(C)(C)C)CCNC(=O)NCC(N=C1N([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)C=NC1=1)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 XKTUCVHQBLNEGR-JRFMUSTFSA-N 0.000 claims 1
ICRSGKCZRPLNIP-CQFMLMEWSA-N 1-[[6-[2,2-bis(3-methylphenyl)ethylamino]-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]methyl]-3-[2-[di(propan-2-yl)amino]ethyl]urea Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=NC(CNC(=O)NCCN(C(C)C)C(C)C)=NC=1NCC(C=1C=C(C)C=CC=1)C1=CC=CC(C)=C1 ICRSGKCZRPLNIP-CQFMLMEWSA-N 0.000 claims 1
YSMMERZHLJADJD-NWNYMGESSA-N 1-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purin-2-yl]methyl]-3-(1-pyridin-2-ylpiperidin-4-yl)urea Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(CNC(=O)NC3CCN(CC3)C=3N=CC=CC=3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 YSMMERZHLJADJD-NWNYMGESSA-N 0.000 claims 1
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HXMMICXFHMTAPU-CIBJAQMISA-N 1-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purin-2-yl]methyl]-3-[2-(2,2,6,6-tetramethylpiperidin-1-yl)ethyl]urea Chemical compound CC1(C)CCCC(C)(C)N1CCNC(=O)NCC1=NC(NCC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 HXMMICXFHMTAPU-CIBJAQMISA-N 0.000 claims 1
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230000007774 longterm Effects 0.000 description 1
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210000002540 macrophage Anatomy 0.000 description 1
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229910052749 magnesium Inorganic materials 0.000 description 1
235000001055 magnesium Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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238000001819 mass spectrum Methods 0.000 description 1
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CURJNMSGPBXOGK-UHFFFAOYSA-N n',n'-di(propan-2-yl)ethane-1,2-diamine Chemical compound CC(C)N(C(C)C)CCN CURJNMSGPBXOGK-UHFFFAOYSA-N 0.000 description 1
CZFWNWMZKPIARS-UHFFFAOYSA-N n',n'-dicyclopentylethane-1,2-diamine;hydrochloride Chemical compound Cl.C1CCCC1N(CCN)C1CCCC1 CZFWNWMZKPIARS-UHFFFAOYSA-N 0.000 description 1
HSWIJDIPZYVNBW-UHFFFAOYSA-N n'-cyclopentyl-n'-propan-2-ylethane-1,2-diamine Chemical compound NCCN(C(C)C)C1CCCC1 HSWIJDIPZYVNBW-UHFFFAOYSA-N 0.000 description 1
JSLRFUPUTGKVFA-UHFFFAOYSA-N n'-tert-butyl-n'-cyclohexylethane-1,2-diamine Chemical compound NCCN(C(C)(C)C)C1CCCCC1 JSLRFUPUTGKVFA-UHFFFAOYSA-N 0.000 description 1
DTYDSPSUBICJOW-UHFFFAOYSA-N n-[2-(2,2,6,6-tetramethylpiperidin-1-yl)ethyl]imidazole-1-carboxamide Chemical compound CC1(C)CCCC(C)(C)N1CCNC(=O)N1C=NC=C1 DTYDSPSUBICJOW-UHFFFAOYSA-N 0.000 description 1
ADKOVLNGFDYSMN-UHFFFAOYSA-N n-[2-(4-propan-2-ylpiperidin-1-yl)ethyl]imidazole-1-carboxamide Chemical compound C1CC(C(C)C)CCN1CCNC(=O)N1C=NC=C1 ADKOVLNGFDYSMN-UHFFFAOYSA-N 0.000 description 1
HCEZZNPOKGQOEQ-UHFFFAOYSA-N n-[2-[2-methylpropyl(pentan-3-yl)amino]ethyl]imidazole-1-carboxamide Chemical compound CCC(CC)N(CC(C)C)CCNC(=O)N1C=CN=C1 HCEZZNPOKGQOEQ-UHFFFAOYSA-N 0.000 description 1
MTEWAFVECQBILW-UHFFFAOYSA-N n-tert-butylcyclohexanamine Chemical compound CC(C)(C)NC1CCCCC1 MTEWAFVECQBILW-UHFFFAOYSA-N 0.000 description 1
NVSYANRBXPURRQ-UHFFFAOYSA-N naphthalen-1-ylmethanamine Chemical compound C1=CC=C2C(CN)=CC=CC2=C1 NVSYANRBXPURRQ-UHFFFAOYSA-N 0.000 description 1
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
230000011242 neutrophil chemotaxis Effects 0.000 description 1
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QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
AUGSPKKIWPASMB-UHFFFAOYSA-N oxolan-3-yl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1CCOC1 AUGSPKKIWPASMB-UHFFFAOYSA-N 0.000 description 1
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NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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WTWWXOGTJWMJHI-UHFFFAOYSA-N perflubron Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)Br WTWWXOGTJWMJHI-UHFFFAOYSA-N 0.000 description 1
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239000011886 peripheral blood Substances 0.000 description 1
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NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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239000011591 potassium Substances 0.000 description 1
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OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
235000011151 potassium sulphates Nutrition 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
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238000000746 purification Methods 0.000 description 1
239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
239000003642 reactive oxygen metabolite Substances 0.000 description 1
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238000012552 review Methods 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
125000005920 sec-butoxy group Chemical group 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000004062 sedimentation Methods 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
229960001790 sodium citrate Drugs 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
239000004296 sodium metabisulphite Substances 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
235000019337 sorbitan trioleate Nutrition 0.000 description 1
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238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 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
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000000451 tissue damage Effects 0.000 description 1
231100000827 tissue damage Toxicity 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Pulmonology (AREA)
Dermatology (AREA)
Endocrinology (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Neurosurgery (AREA)
Cardiology (AREA)
Reproductive Health (AREA)
Biochemistry (AREA)
Gynecology & Obstetrics (AREA)
Genetics & Genomics (AREA)
Pain & Pain Management (AREA)
Biotechnology (AREA)
Molecular Biology (AREA)
Emergency Medicine (AREA)
Obesity (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Pregnancy & Childbirth (AREA)
Rheumatology (AREA)
Hematology (AREA)

SK1733-2002A 2000-06-27 2001-06-14 Purínové deriváty SK17332002A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0015727.1A GB0015727D0 (en)	2000-06-27	2000-06-27	Purine derivatives
PCT/IB2001/001064 WO2002000676A1 (en)	2000-06-27	2001-06-14	Purine derivatives

Publications (1)

Publication Number	Publication Date
SK17332002A3 true SK17332002A3 (sk)	2004-03-02

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Application Number	Title	Priority Date	Filing Date
SK1733-2002A SK17332002A3 (sk)	2000-06-27	2001-06-14	Purínové deriváty

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EP (1)	EP1296996B1 (pt)
JP (1)	JP2004501929A (pt)
KR (1)	KR20030036248A (pt)
CN (1)	CN1432020A (pt)
AP (1)	AP1372A (pt)
AR (1)	AR028759A1 (pt)
AT (1)	ATE267836T1 (pt)
AU (1)	AU2001264164A1 (pt)
BG (1)	BG107171A (pt)
BR (1)	BR0111912A (pt)
CA (1)	CA2412564C (pt)
CZ (1)	CZ20023992A3 (pt)
DE (1)	DE60103537T2 (pt)
DK (1)	DK1296996T3 (pt)
DO (1)	DOP2001000195A (pt)
EA (1)	EA200201291A1 (pt)
EC (1)	ECSP024396A (pt)
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ES (1)	ES2220775T3 (pt)
GB (1)	GB0015727D0 (pt)
GT (1)	GT200100119A (pt)
HR (1)	HRP20020995A2 (pt)
HU (1)	HUP0301389A3 (pt)
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IS (1)	IS6580A (pt)
MA (1)	MA26918A1 (pt)
MX (1)	MXPA03000078A (pt)
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NZ (1)	NZ521867A (pt)
OA (1)	OA12294A (pt)
PA (1)	PA8521001A1 (pt)
PE (1)	PE20020213A1 (pt)
PL (1)	PL361384A1 (pt)
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SI (1)	SI1296996T1 (pt)
SK (1)	SK17332002A3 (pt)
SV (1)	SV2002000507A (pt)
TN (1)	TNSN01096A1 (pt)
TR (1)	TR200401622T4 (pt)
UY (1)	UY26797A1 (pt)
WO (1)	WO2002000676A1 (pt)
ZA (1)	ZA200209557B (pt)

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EP1421078B1 (en)	2001-08-14	2006-09-27	Eli Lilly And Company	Indole derivatives as beta-3 adrenergic agonists for the treatment of type 2 diabetes
SE0201980D0 (sv) *	2002-06-24	2002-06-24	Astrazeneca Ab	Novel compounds
WO2004028530A1 (en)	2002-09-26	2004-04-08	Bristol-Myers Squibb Company	N-substituted heterocyclic amines as modulators of chemokine receptor activity
TW200519106A (en)	2003-05-02	2005-06-16	Novartis Ag	Organic compounds
GB0401334D0 (en)	2004-01-21	2004-02-25	Novartis Ag	Organic compounds
GB0411056D0 (en)	2004-05-18	2004-06-23	Novartis Ag	Organic compounds
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2000
- 2000-06-27 GB GBGB0015727.1A patent/GB0015727D0/en not_active Ceased
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Also Published As

Publication number	Publication date
CA2412564A1 (en)	2002-01-03
ECSP024396A (es)	2003-02-06
CN1432020A (zh)	2003-07-23
TNSN01096A1 (fr)	2005-11-10
NO20025975L (no)	2002-12-12
PA8521001A1 (es)	2002-04-25
DE60103537D1 (de)	2004-07-01
PE20020213A1 (es)	2002-03-19
HRP20020995A2 (en)	2005-02-28
IL152529A0 (en)	2003-05-29
ZA200209557B (en)	2003-12-02
DE60103537T2 (de)	2005-07-07
IS6580A (is)	2002-10-10
CZ20023992A3 (cs)	2003-12-17
TR200401622T4 (tr)	2004-08-23
JP2004501929A (ja)	2004-01-22
AU2001264164A1 (en)	2002-01-08
AP1372A (en)	2005-02-21
EP1296996A1 (en)	2003-04-02
PL361384A1 (en)	2004-10-04
GB0015727D0 (en)	2000-08-16
ATE267836T1 (de)	2004-06-15
HUP0301389A3 (en)	2005-02-28
MXPA03000078A (es)	2003-08-19
EP1296996B1 (en)	2004-05-26
CA2412564C (en)	2007-10-02
PT1296996E (pt)	2004-08-31
KR20030036248A (ko)	2003-05-09
OA12294A (en)	2003-11-14
HUP0301389A2 (hu)	2003-08-28
SI1296996T1 (en)	2004-10-31
UY26797A1 (es)	2002-01-31
EE200200712A (et)	2004-06-15
ES2220775T3 (es)	2004-12-16
SV2002000507A (es)	2002-07-03
EA200201291A1 (ru)	2003-04-24
GT200100119A (es)	2002-01-31
AR028759A1 (es)	2003-05-21
BG107171A (en)	2003-07-31
NZ521867A (en)	2004-04-30
DOP2001000195A (es)	2002-05-15
DK1296996T3 (da)	2004-08-16
MA26918A1 (fr)	2004-12-20
WO2002000676A1 (en)	2002-01-03
NO20025975D0 (no)	2002-12-12
BR0111912A (pt)	2003-05-13

Publication	Publication Date	Title
SK17332002A3 (sk)	2004-03-02	Purínové deriváty
AU2001260537B2 (en)	2006-05-25	2-aminocarbonyl-9H-purine derivatives
CZ20021179A3 (cs)	2003-04-16	Purinové deriváty
AU764106B2 (en)	2003-08-07	Purine derivatives
SK4842002A3 (en)	2003-06-03	Purine derivatives
US6525032B2 (en)	2003-02-25	Purine derivatives
US6921753B2 (en)	2005-07-26	Purine derivatives
JP2002527524A (ja)	2002-08-27	アデニン誘導体
US6753322B2 (en)	2004-06-22	2-aminocarbonyl-9H-purine derivatives
HK1089447B (en)	2008-08-22	A process for the preparation of 2-aminocarbonyl-9h-purine derivatives and the intermediates thereof