SK164397A3 - Method for preparing n-monosubstituted and n,n'-disubstituted unsymmetrical cyclic ureas - Google Patents

Method for preparing n-monosubstituted and n,n'-disubstituted unsymmetrical cyclic ureas Download PDF

Info

Publication number: SK164397A3
Authority: SK; Slovakia
Prior art keywords: substituted; alkyl; group; radicals; carbon atoms
Prior art date: 1995-06-07

Application number

SK1643-97A

Other languages

English (en)

Slovak (sk)

Inventor

James David Rodgers

Jung-Hui Sun

Original Assignee

Du Pont Merck Pharma

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.)

1995-06-07

Filing date

1996-06-06

Publication date

2000-04-10

1996-06-06 Application filed by Du Pont Merck Pharma filed Critical Du Pont Merck Pharma

2000-04-10 Publication of SK164397A3 publication Critical patent/SK164397A3/sk

Links

-1 cyclic ureas Chemical class 0.000 title claims abstract description 549
238000000034 method Methods 0.000 title claims description 52
235000013877 carbamide Nutrition 0.000 title claims description 27
125000004432 carbon atom Chemical group C* 0.000 claims description 152
150000001875 compounds Chemical class 0.000 claims description 146
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 143
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 137
229910052757 nitrogen Inorganic materials 0.000 claims description 136
125000000217 alkyl group Chemical group 0.000 claims description 116
125000000623 heterocyclic group Chemical group 0.000 claims description 101
150000003254 radicals Chemical class 0.000 claims description 99
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
125000001424 substituent group Chemical group 0.000 claims description 67
229910052736 halogen Inorganic materials 0.000 claims description 64
150000002367 halogens Chemical class 0.000 claims description 63
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 62
229910052799 carbon Inorganic materials 0.000 claims description 59
229910052739 hydrogen Inorganic materials 0.000 claims description 51
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 51
229910052760 oxygen Inorganic materials 0.000 claims description 50
125000004093 cyano group Chemical group *C#N 0.000 claims description 48
239000002253 acid Substances 0.000 claims description 47
239000001257 hydrogen Substances 0.000 claims description 47
239000001301 oxygen Substances 0.000 claims description 43
125000006239 protecting group Chemical group 0.000 claims description 42
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 39
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 36
125000003710 aryl alkyl group Chemical group 0.000 claims description 36
125000000753 cycloalkyl group Chemical group 0.000 claims description 35
125000005842 heteroatom Chemical group 0.000 claims description 35
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 34
229910052717 sulfur Chemical group 0.000 claims description 33
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 description 31
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 31
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 31
238000006243 chemical reaction Methods 0.000 claims description 31
125000004430 oxygen atom Chemical group O* 0.000 claims description 31
239000003153 chemical reaction reagent Substances 0.000 claims description 29
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 28
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 28
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
125000003118 aryl group Chemical group 0.000 claims description 25
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 25
125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 24
125000004434 sulfur atom Chemical group 0.000 claims description 23
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 22
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 22
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 22
239000002168 alkylating agent Substances 0.000 claims description 21
229940100198 alkylating agent Drugs 0.000 claims description 21
150000002431 hydrogen Chemical class 0.000 claims description 21
239000011593 sulfur Chemical group 0.000 claims description 21
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 20
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 20
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 19
150000003839 salts Chemical group 0.000 claims description 19
239000002904 solvent Substances 0.000 claims description 19
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
239000000010 aprotic solvent Substances 0.000 claims description 18
229910052794 bromium Inorganic materials 0.000 claims description 18
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 17
125000000468 ketone group Chemical group 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
239000000460 chlorine Substances 0.000 claims description 16
229910052801 chlorine Inorganic materials 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
229910052731 fluorine Inorganic materials 0.000 claims description 16
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 15
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 15
229930194542 Keto Natural products 0.000 claims description 15
150000001413 amino acids Chemical class 0.000 claims description 15
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
125000002837 carbocyclic group Chemical group 0.000 claims description 15
239000003795 chemical substances by application Substances 0.000 claims description 15
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 14
125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 13
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
239000011737 fluorine Chemical group 0.000 claims description 13
229940124530 sulfonamide Drugs 0.000 claims description 13
150000003456 sulfonamides Chemical class 0.000 claims description 13
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
125000001188 haloalkyl group Chemical group 0.000 claims description 12
229920006395 saturated elastomer Polymers 0.000 claims description 12
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 11
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
125000000160 oxazolidinyl group Chemical group 0.000 claims description 11
125000003226 pyrazolyl group Chemical group 0.000 claims description 11
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 10
125000005620 boronic acid group Chemical group 0.000 claims description 10
150000001721 carbon Chemical group 0.000 claims description 10
125000004076 pyridyl group Chemical group 0.000 claims description 10
238000010992 reflux Methods 0.000 claims description 10
125000003831 tetrazolyl group Chemical group 0.000 claims description 10
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 9
125000004438 haloalkoxy group Chemical group 0.000 claims description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 8
125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
125000000000 cycloalkoxy group Chemical group 0.000 claims description 8
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 8
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 7
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 7
125000002541 furyl group Chemical group 0.000 claims description 7
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 7
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 7
150000002923 oximes Chemical class 0.000 claims description 7
125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
125000000168 pyrrolyl group Chemical group 0.000 claims description 7
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
125000004306 triazinyl group Chemical group 0.000 claims description 7
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 6
125000004175 fluorobenzyl group Chemical group 0.000 claims description 6
125000000524 functional group Chemical group 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
125000001041 indolyl group Chemical group 0.000 claims description 6
PCKPVGOLPKLUHR-UHFFFAOYSA-N indoxyl Chemical group C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
125000000335 thiazolyl group Chemical group 0.000 claims description 6
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 5
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 5
125000000565 sulfonamide group Chemical group 0.000 claims description 5
125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
125000005336 allyloxy group Chemical group 0.000 claims description 4
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
125000000262 haloalkenyl group Chemical group 0.000 claims description 4
125000000232 haloalkynyl group Chemical group 0.000 claims description 4
125000006289 hydroxybenzyl group Chemical group 0.000 claims description 4
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 4
XYMVZPOXZCDCNP-UHFFFAOYSA-N sulfamoyl cyanide Chemical compound NS(=O)(=O)C#N XYMVZPOXZCDCNP-UHFFFAOYSA-N 0.000 claims description 4
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 3
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 3
125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 3
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
150000007942 carboxylates Chemical class 0.000 claims description 3
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
239000012380 dealkylating agent Substances 0.000 claims description 3
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
150000004820 halides Chemical class 0.000 claims description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 3
239000000651 prodrug Chemical group 0.000 claims description 3
229940002612 prodrug Drugs 0.000 claims description 3
125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 2
HXELGNKCCDGMMN-UHFFFAOYSA-N [F].[Cl] Chemical group [F].[Cl] HXELGNKCCDGMMN-UHFFFAOYSA-N 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
HBWDWGMBZIFBQE-UHFFFAOYSA-N benzylboronic acid Chemical group OB(O)CC1=CC=CC=C1 HBWDWGMBZIFBQE-UHFFFAOYSA-N 0.000 claims description 2
125000006278 bromobenzyl group Chemical group 0.000 claims description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
125000004803 chlorobenzyl group Chemical group 0.000 claims description 2
125000002946 cyanobenzyl group Chemical group 0.000 claims description 2
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 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
125000006480 iodobenzyl group Chemical group 0.000 claims description 2
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000006178 methyl benzyl group Chemical group 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000003544 oxime group Chemical group 0.000 claims description 2
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 claims description 2
125000006187 phenyl benzyl group Chemical group 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
229910052796 boron Inorganic materials 0.000 claims 2
150000001804 chlorine Chemical class 0.000 claims 2
ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical group C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 claims 1
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
239000005977 Ethylene Substances 0.000 claims 1
244000309464 bull Species 0.000 claims 1
238000003776 cleavage reaction Methods 0.000 claims 1
125000006287 difluorobenzyl group Chemical group 0.000 claims 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
150000005837 radical ions Chemical class 0.000 claims 1
230000000717 retained effect Effects 0.000 claims 1
230000007017 scission Effects 0.000 claims 1
PFXVKGGZWQQTSE-UHFFFAOYSA-N sulfuryl dicyanide Chemical class N#CS(=O)(=O)C#N PFXVKGGZWQQTSE-UHFFFAOYSA-N 0.000 claims 1
239000004030 hiv protease inhibitor Substances 0.000 abstract description 9
229940122440 HIV protease inhibitor Drugs 0.000 abstract description 2
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 30
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
230000015572 biosynthetic process Effects 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
239000002585 base Substances 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
238000003786 synthesis reaction Methods 0.000 description 22
ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical compound OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 description 21
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
239000000203 mixture Substances 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
235000001014 amino acid Nutrition 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
239000004202 carbamide Substances 0.000 description 11
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
230000029936 alkylation Effects 0.000 description 10
238000005804 alkylation reaction Methods 0.000 description 10
125000004122 cyclic group Chemical group 0.000 description 10
108090000765 processed proteins & peptides Proteins 0.000 description 10
150000004985 diamines Chemical class 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
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230000001678 irradiating effect Effects 0.000 description 1
230000007794 irritation Effects 0.000 description 1
229940045996 isethionic acid Drugs 0.000 description 1
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
ULYZAYCEDJDHCC-UHFFFAOYSA-N isopropyl chloride Chemical compound CC(C)Cl ULYZAYCEDJDHCC-UHFFFAOYSA-N 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
238000005304 joining Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000007788 liquid Substances 0.000 description 1
XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
229910052808 lithium carbonate Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate 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
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
229960002523 mercuric chloride Drugs 0.000 description 1
LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
CZXGXYBOQYQXQD-UHFFFAOYSA-N methyl benzenesulfonate Chemical compound COS(=O)(=O)C1=CC=CC=C1 CZXGXYBOQYQXQD-UHFFFAOYSA-N 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
CIXSDMKDSYXUMJ-UHFFFAOYSA-N n,n-diethylcyclohexanamine Chemical compound CCN(CC)C1CCCCC1 CIXSDMKDSYXUMJ-UHFFFAOYSA-N 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
150000002829 nitrogen Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
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
125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
239000000816 peptidomimetic Substances 0.000 description 1
125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
MKIFFISYTYREEU-UHFFFAOYSA-N phenyl 2h-tetrazole-5-carboxylate Chemical compound N=1N=NNC=1C(=O)OC1=CC=CC=C1 MKIFFISYTYREEU-UHFFFAOYSA-N 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
PWXJULSLLONQHY-UHFFFAOYSA-N phenylcarbamic acid Chemical compound OC(=O)NC1=CC=CC=C1 PWXJULSLLONQHY-UHFFFAOYSA-N 0.000 description 1
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
229920005990 polystyrene resin Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
238000003908 quality control method Methods 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
230000005855 radiation Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
229950000244 sulfanilic acid Drugs 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 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
NPDBDJFLKKQMCM-UHFFFAOYSA-N tert-butylglycine Chemical compound CC(C)(C)C(N)C(O)=O NPDBDJFLKKQMCM-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/04—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- 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)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pyridine Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Enzymes And Modification Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

SK1643-97A 1995-06-07 1996-06-06 Method for preparing n-monosubstituted and n,n'-disubstituted unsymmetrical cyclic ureas SK164397A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/481,683 US5532357A (en)	1995-06-07	1995-06-07	Method for preparing N-monosubstituted and N,N'-disubstituted unsymmetrical cyclic ureas
PCT/US1996/009021 WO1996040652A1 (en)	1995-06-07	1996-06-06	Method for preparing n-monosubstituted and n,n'-disubstituted unsymmetrical cyclic ureas

Publications (1)

Publication Number	Publication Date
SK164397A3 true SK164397A3 (en)	2000-04-10

Family

ID=23912954

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1643-97A SK164397A3 (en)	1995-06-07	1996-06-06	Method for preparing n-monosubstituted and n,n'-disubstituted unsymmetrical cyclic ureas

Country Status (26)

Country	Link
US (1)	US5532357A (es)
EP (2)	EP1029859A1 (es)
JP (1)	JPH11506779A (es)
KR (1)	KR19990022467A (es)
CN (1)	CN1192209A (es)
AR (1)	AR002384A1 (es)
AU (1)	AU704535B2 (es)
BR (1)	BR9609493A (es)
CA (1)	CA2223391A1 (es)
CZ (1)	CZ381997A3 (es)
EA (1)	EA000363B1 (es)
EE (1)	EE9700330A (es)
HR (1)	HRP960259A2 (es)
HU (1)	HUP9900913A2 (es)
IL (1)	IL122424A0 (es)
LT (1)	LT4381B (es)
LV (1)	LV12045B (es)
MX (1)	MX9709652A (es)
NO (1)	NO975679L (es)
NZ (1)	NZ309648A (es)
PL (1)	PL323993A1 (es)
SI (1)	SI9620077A (es)
SK (1)	SK164397A3 (es)
TW (1)	TW358091B (es)
WO (1)	WO1996040652A1 (es)
ZA (1)	ZA964847B (es)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5466797A (en) *	1994-06-30	1995-11-14	The Du Pont Merck Pharmaceutical Company	Intermediates for the preparation of cyclic urea
US6054597A (en) *	1995-11-14	2000-04-25	Dupont Pharmaceuticals	Processes and intermediates for the preparation of cyclic urea HIV protease inhibitors
DE69723456T2 (de) *	1996-11-08	2004-05-27	Bristol-Myers Squibb Pharma Co.	1-(3-aminoindazol-5-yl)-3-phenylmethyl cyclische harnstoffe und ihre verwendung als hiv protease inhibitoren
US5932570A (en) *	1996-11-08	1999-08-03	Dupont Pharmaceuticals Company	1-(3-aminoindazol-5-yl)-3-phenylmethyl-cyclic ureas useful as HIV protease inhibitors
US6218386B1 (en)	1996-11-08	2001-04-17	Dupont Pharmaceuticals	A1-(3-aminoindazol-5-yl)-3 butyl-cyclic urea useful as a HIV protease inhibitor
WO1998043969A1 (en) *	1997-03-31	1998-10-08	Dupont Pharmaceuticals Company	Indazoles of cyclic ureas useful as hiv protease inhibitors
US6218534B1 (en) *	1997-10-06	2001-04-17	Dupont Pharmaceuticals Company	Preparation of asymmetric cyclic ureas through a monoacylated diamine intermediate
WO2000000479A1 (en) *	1998-06-30	2000-01-06	Du Pont Pharmaceuticals Company	1,3-benzodiazepin-2-ones and 1,3-benzoxazepin-2-ones useful as hiv reverse transcriptase inhibitors
CA2370141A1 (en)	1999-05-26	2000-12-07	James D. Rodgers	1,4-benzodiazepin-2-ones useful as hiv reverse transcriptase inhibitors
US6313110B1 (en) *	1999-06-02	2001-11-06	Dupont Pharmaceuticals Company	Substituted 2H-1,3-diazapin-2-one useful as an HIV protease inhibitor
FR2810039B1 (fr) *	2000-06-13	2007-05-25	Centre Nat Rech Scient	Composes urees cycliques et leur procede de preparation
US7015214B2 (en) *	2001-03-28	2006-03-21	Bristol-Myers Squibb Pharma Company	Cyanamide, alkoxyamino, and urea derivatives of 1,3-benzodiazepine as HIV reverse transcriptase inhibitors
US20080031951A1 (en)	2005-12-29	2008-02-07	Gilles Guichard	Compositions and methods for the inhibition of phospholipase A2

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2120925A1 (en) *	1991-10-11	1993-04-15	Patrick Yuk-Sun Lam	Substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors
US5610294A (en) *	1991-10-11	1997-03-11	The Du Pont Merck Pharmaceutical Company	Substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors
US5430043A (en) *	1993-08-24	1995-07-04	G. D. Searle & Co.	Platelet aggregation inhibitors
US5466797A (en) *	1994-06-30	1995-11-14	The Du Pont Merck Pharmaceutical Company	Intermediates for the preparation of cyclic urea
US5530124A (en) *	1994-06-30	1996-06-25	The Dupont Merck Pharmaceutical Company	Method for preparing cyclic ureas and their use for the synthesis of HIV protease inhibitors
US5532356A (en) *	1995-06-06	1996-07-02	The Dupont Merck Pharmaceutical Company	Method for preparing N,N'-disubstituted cyclic ureas
US7344671B2 (en)	2003-11-26	2008-03-18	Glopak Inc.	Optical sealing clamp and a method for sealing and cutting polymeric sheets with a laser
US7369013B2 (en)	2005-04-06	2008-05-06	Avago Technologies Wireless Ip Pte Ltd	Acoustic resonator performance enhancement using filled recessed region

1995
- 1995-06-07 US US08/481,683 patent/US5532357A/en not_active Expired - Lifetime
1996
- 1996-06-06 EA EA199800034A patent/EA000363B1/ru not_active IP Right Cessation
- 1996-06-06 CZ CZ973819A patent/CZ381997A3/cs unknown
- 1996-06-06 KR KR1019970708948A patent/KR19990022467A/ko not_active Withdrawn
- 1996-06-06 IL IL12242496A patent/IL122424A0/xx unknown
- 1996-06-06 WO PCT/US1996/009021 patent/WO1996040652A1/en not_active Ceased
- 1996-06-06 SK SK1643-97A patent/SK164397A3/sk unknown
- 1996-06-06 NZ NZ309648A patent/NZ309648A/en unknown
- 1996-06-06 SI SI9620077A patent/SI9620077A/sl unknown
- 1996-06-06 HR HR481,683A patent/HRP960259A2/hr not_active Application Discontinuation
- 1996-06-06 AU AU59868/96A patent/AU704535B2/en not_active Ceased
- 1996-06-06 HU HU9900913A patent/HUP9900913A2/hu unknown
- 1996-06-06 CA CA002223391A patent/CA2223391A1/en not_active Abandoned
- 1996-06-06 EP EP00109875A patent/EP1029859A1/en not_active Withdrawn
- 1996-06-06 MX MX9709652A patent/MX9709652A/es unknown
- 1996-06-06 EP EP96917212A patent/EP0837855A4/en not_active Withdrawn
- 1996-06-06 BR BR9609493A patent/BR9609493A/pt not_active Application Discontinuation
- 1996-06-06 JP JP9501440A patent/JPH11506779A/ja active Pending
- 1996-06-06 EE EE9700330A patent/EE9700330A/xx unknown
- 1996-06-06 PL PL96323993A patent/PL323993A1/xx unknown
- 1996-06-06 CN CN96195932A patent/CN1192209A/zh active Pending
- 1996-06-07 ZA ZA9604847A patent/ZA964847B/xx unknown
- 1996-06-07 AR AR10302696A patent/AR002384A1/es unknown
- 1996-07-06 TW TW085108193A patent/TW358091B/zh active
1997
- 1997-12-03 LT LT97-188A patent/LT4381B/lt not_active IP Right Cessation
- 1997-12-05 NO NO975679A patent/NO975679L/no not_active Application Discontinuation
1998
- 1998-01-28 LV LVP-97-248A patent/LV12045B/en unknown

Also Published As

Publication number	Publication date
LT4381B (lt)	1998-09-25
PL323993A1 (en)	1998-04-27
HUP9900913A2 (hu)	1999-09-28
LT97188A (en)	1998-04-27
LV12045B (en)	1998-09-20
CN1192209A (zh)	1998-09-02
CZ381997A3 (cs)	1999-01-13
BR9609493A (pt)	1999-03-02
KR19990022467A (ko)	1999-03-25
CA2223391A1 (en)	1996-12-19
LV12045A (lv)	1998-05-20
NZ309648A (en)	1998-09-24
MX9709652A (es)	1998-03-29
AU5986896A (en)	1996-12-30
JPH11506779A (ja)	1999-06-15
TW358091B (en)	1999-05-11
EA199800034A1 (ru)	1998-08-27
EP0837855A4 (en)	1998-09-02
HRP960259A2 (en)	1997-10-31
AR002384A1 (es)	1998-03-11
WO1996040652A1 (en)	1996-12-19
IL122424A0 (en)	1998-06-15
US5532357A (en)	1996-07-02
EE9700330A (et)	1998-06-15
EA000363B1 (ru)	1999-06-24
NO975679L (no)	1998-02-02
ZA964847B (en)	1997-12-08
AU704535B2 (en)	1999-04-29
SI9620077A (sl)	1998-08-31
NO975679D0 (no)	1997-12-05
EP1029859A1 (en)	2000-08-23
EP0837855A1 (en)	1998-04-29

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