SK14893A3 - Process for preparing sulfoamidocarboxamides and their pharmaceutical compositions - Google Patents

Process for preparing sulfoamidocarboxamides and their pharmaceutical compositions Download PDF

Info

Publication number: SK14893A3
Authority: SK; Slovakia
Prior art keywords: group; acid; formula; aminoiminomethyl; piperidin
Prior art date: 1992-03-06

Application number

SK148-93A

Other languages

English (en)

Slovak (sk)

Inventor

Jean Ackermann

David Banner

Klaus Gubernator

Kurt Hilpert

Gerard Schmid

Original Assignee

Hoffmann La Roche

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.)

1992-03-06

Filing date

1993-03-01

Publication date

1993-11-10

1993-03-01 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1993-11-10 Publication of SK14893A3 publication Critical patent/SK14893A3/sk

Links

238000004519 manufacturing process Methods 0.000 title claims description 33
239000008194 pharmaceutical composition Substances 0.000 title 1
-1 hydroxy, carboxy Chemical group 0.000 claims description 316
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 143
150000001875 compounds Chemical class 0.000 claims description 107
125000000217 alkyl group Chemical group 0.000 claims description 85
239000001257 hydrogen Substances 0.000 claims description 66
229910052739 hydrogen Inorganic materials 0.000 claims description 66
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 57
ZYUZLEUJKZZXNN-UHFFFAOYSA-N C1=CC(CC(N)C(O)=O)=CC=C1OS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 Chemical group C1=CC(CC(N)C(O)=O)=CC=C1OS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 ZYUZLEUJKZZXNN-UHFFFAOYSA-N 0.000 claims description 42
239000002253 acid Substances 0.000 claims description 40
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
150000002431 hydrogen Chemical class 0.000 claims description 30
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 27
125000000753 cycloalkyl group Chemical group 0.000 claims description 26
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
125000003118 aryl group Chemical group 0.000 claims description 22
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
125000006317 cyclopropyl amino group Chemical group 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 20
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 18
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 15
150000001412 amines Chemical class 0.000 claims description 15
125000004494 ethyl ester group Chemical group 0.000 claims description 15
125000001072 heteroaryl group Chemical group 0.000 claims description 15
238000000034 method Methods 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 14
SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 claims description 11
108090000190 Thrombin Proteins 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000003831 tetrazolyl group Chemical group 0.000 claims description 9
229960004072 thrombin Drugs 0.000 claims description 9
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 8
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 8
SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims description 8
239000000825 pharmaceutical preparation Substances 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000001589 carboacyl group Chemical group 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
239000004471 Glycine Substances 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000006309 butyl amino group Chemical group 0.000 claims description 6
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
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 6
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
101150065749 Churc1 gene Proteins 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
239000012453 solvate Substances 0.000 claims description 5
125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
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 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
230000015271 coagulation Effects 0.000 claims description 4
238000005345 coagulation Methods 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
210000002381 plasma Anatomy 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
239000011593 sulfur Substances 0.000 claims description 4
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
108010049003 Fibrinogen Proteins 0.000 claims description 3
102000008946 Fibrinogen Human genes 0.000 claims description 3
XPISQLSFZNSNJN-AVRDEDQJSA-N NN=CN1C[C@@H](CCC1)CNC(=O)C[C@@H](C(=O)N(C1CC1)CC(=O)O)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C Chemical compound NN=CN1C[C@@H](CCC1)CNC(=O)C[C@@H](C(=O)N(C1CC1)CC(=O)O)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C XPISQLSFZNSNJN-AVRDEDQJSA-N 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
229940012952 fibrinogen Drugs 0.000 claims description 3
239000000543 intermediate Substances 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 3
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 2
POCFHLUFHIPSHK-IAXKEJLGSA-N 2-[cyclopropyl-[(2s)-4-[(4-methanehydrazonoylmorpholin-2-yl)methylamino]-2-naphthalen-2-ylsulfonyl-4-oxobutanoyl]amino]acetic acid Chemical compound C1N(C=NN)CCOC1CNC(=O)C[C@H](S(=O)(=O)C=1C=C2C=CC=CC2=CC=1)C(=O)N(CC(O)=O)C1CC1 POCFHLUFHIPSHK-IAXKEJLGSA-N 0.000 claims description 2
OGHGMOGZDMYICC-PXNSSMCTSA-N 3-[[(2S)-2-[(4-cyanophenyl)sulfonylamino]-4-[[(3S)-1-methanehydrazonoylpiperidin-3-yl]amino]-4-oxobutanoyl]-cyclopropylamino]propanoic acid Chemical compound C1N(C=NN)CCC[C@@H]1NC(=O)C[C@@H](C(=O)N(CCC(O)=O)C1CC1)NS(=O)(=O)C1=CC=C(C#N)C=C1 OGHGMOGZDMYICC-PXNSSMCTSA-N 0.000 claims description 2
MAZSLWRQOOOQHK-LPHOPBHVSA-N 3-[[(2s)-2-[(4-carbamoylphenyl)sulfonylamino]-4-[[(3s)-1-methanehydrazonoylpiperidin-3-yl]amino]-4-oxobutanoyl]-cyclopropylamino]propanoic acid Chemical compound C1N(C=NN)CCC[C@@H]1NC(=O)C[C@@H](C(=O)N(CCC(O)=O)C1CC1)NS(=O)(=O)C1=CC=C(C(N)=O)C=C1 MAZSLWRQOOOQHK-LPHOPBHVSA-N 0.000 claims description 2
102100038239 Protein Churchill Human genes 0.000 claims description 2
125000003302 alkenyloxy group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
SIVVHUQWDOGLJN-UHFFFAOYSA-N ethylsulfamic acid Chemical compound CCNS(O)(=O)=O SIVVHUQWDOGLJN-UHFFFAOYSA-N 0.000 claims description 2
150000004677 hydrates Chemical class 0.000 claims description 2
239000003112 inhibitor Substances 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
OPRUAYKXGCLCMQ-QHEXFSSWSA-N C[C@@H](C(O)=O)N(C1CC1)C(C(CC(NC[C@H](CCC1)CN1C=NN)=O)NS(C1=CC2=CC=CC=C2C=C1)(=O)=O)=O Chemical compound C[C@@H](C(O)=O)N(C1CC1)C(C(CC(NC[C@H](CCC1)CN1C=NN)=O)NS(C1=CC2=CC=CC=C2C=C1)(=O)=O)=O OPRUAYKXGCLCMQ-QHEXFSSWSA-N 0.000 claims 1
230000002862 amidating effect Effects 0.000 claims 1
238000011321 prophylaxis Methods 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 236
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 168
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 153
239000007921 spray Substances 0.000 description 137
150000002500 ions Chemical class 0.000 description 131
239000000243 solution Substances 0.000 description 126
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 107
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 102
239000000203 mixture Substances 0.000 description 102
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 86
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
239000000047 product Substances 0.000 description 57
229960000583 acetic acid Drugs 0.000 description 49
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 47
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
150000002148 esters Chemical class 0.000 description 40
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 40
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
239000000741 silica gel Substances 0.000 description 36
229910002027 silica gel Inorganic materials 0.000 description 36
239000011541 reaction mixture Substances 0.000 description 35
238000006243 chemical reaction Methods 0.000 description 34
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 29
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
239000012071 phase Substances 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
239000012074 organic phase Substances 0.000 description 24
235000019260 propionic acid Nutrition 0.000 description 23
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 23
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
239000007858 starting material Substances 0.000 description 20
239000003480 eluent Substances 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 14
150000007513 acids Chemical class 0.000 description 14
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 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
AOPRFYAPABFRPU-UHFFFAOYSA-N amino(imino)methanesulfonic acid Chemical compound NC(=N)S(O)(=O)=O AOPRFYAPABFRPU-UHFFFAOYSA-N 0.000 description 12
239000000706 filtrate Substances 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 11
238000001035 drying Methods 0.000 description 11
238000001704 evaporation Methods 0.000 description 11
239000002904 solvent Substances 0.000 description 11
238000003756 stirring Methods 0.000 description 11
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 10
230000008020 evaporation Effects 0.000 description 10
ZXDMKFJQAUELAX-ILKKLZGPSA-N (3s)-3-(aminomethyl)piperidine-1-carboximidamide;dihydrochloride Chemical compound Cl.Cl.NC[C@@H]1CCCN(C(N)=N)C1 ZXDMKFJQAUELAX-ILKKLZGPSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
239000000725 suspension Substances 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
238000003776 cleavage reaction Methods 0.000 description 8
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
230000007017 scission Effects 0.000 description 8
239000000126 substance Substances 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 7
239000002585 base Substances 0.000 description 7
150000005690 diesters Chemical class 0.000 description 7
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
229910000343 potassium bisulfate Inorganic materials 0.000 description 7
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 7
229910052939 potassium sulfate Inorganic materials 0.000 description 7
235000011151 potassium sulphates Nutrition 0.000 description 7
238000010898 silica gel chromatography Methods 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
229960002449 glycine Drugs 0.000 description 6
150000004702 methyl esters Chemical class 0.000 description 6
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
WWURAJDQNKIBNL-NRFANRHFSA-N tert-butyl (3s)-4-[cyclopropyl-(2-ethoxy-2-oxoethyl)amino]-3-(naphthalen-2-ylsulfonylamino)-4-oxobutanoate Chemical compound O=C([C@H](CC(=O)OC(C)(C)C)NS(=O)(=O)C=1C=C2C=CC=CC2=CC=1)N(CC(=O)OCC)C1CC1 WWURAJDQNKIBNL-NRFANRHFSA-N 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical class OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 5
GXLBYIBLUCJQPM-UHFFFAOYSA-N (e)-aminomethylidenecarbamic acid Chemical compound N\C=N\C(O)=O GXLBYIBLUCJQPM-UHFFFAOYSA-N 0.000 description 5
PBIUDEUWYGBHDW-UHFFFAOYSA-N 2-chloro-1-pyridin-3-ylethanone;hydrochloride Chemical compound Cl.ClCC(=O)C1=CC=CN=C1 PBIUDEUWYGBHDW-UHFFFAOYSA-N 0.000 description 5
PYXYLLBBIRNRJT-UHFFFAOYSA-N 2-chlorosulfonyloxynaphthalene Chemical compound C1=CC=CC2=CC(OS(=O)(=O)Cl)=CC=C21 PYXYLLBBIRNRJT-UHFFFAOYSA-N 0.000 description 5
JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 5
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UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 1
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DOFXZXIPZBUHDL-UHFFFAOYSA-N tert-butyl 4-amino-4-oxobutanoate Chemical compound CC(C)(C)OC(=O)CCC(N)=O DOFXZXIPZBUHDL-UHFFFAOYSA-N 0.000 description 1
AXNNEAKZXIHZGY-UHFFFAOYSA-N tert-butyl N-cyclopropyl-N-(3-oxobutyl)carbamate Chemical compound C(C)(C)(C)OC(N(CCC(C)=O)C1CC1)=O AXNNEAKZXIHZGY-UHFFFAOYSA-N 0.000 description 1
ZARLKOYQVIKKNV-UHFFFAOYSA-N tert-butyl n-(2-cyanoethyl)-n-cyclopropylcarbamate Chemical compound CC(C)(C)OC(=O)N(CCC#N)C1CC1 ZARLKOYQVIKKNV-UHFFFAOYSA-N 0.000 description 1
VHYXAWLOJGIJPC-UHFFFAOYSA-N tert-butyl n-(piperidin-4-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCNCC1 VHYXAWLOJGIJPC-UHFFFAOYSA-N 0.000 description 1
RBNSTLJMVYYCFL-UHFFFAOYSA-N tert-butyl n-[(1-methanehydrazonoylpiperidin-4-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCN(C=NN)CC1 RBNSTLJMVYYCFL-UHFFFAOYSA-N 0.000 description 1
LLXMKOTWXMKYCL-UHFFFAOYSA-N tert-butyl n-cyclopropyl-n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CCCO)C1CC1 LLXMKOTWXMKYCL-UHFFFAOYSA-N 0.000 description 1
AEEQTSOBTVKZFR-UHFFFAOYSA-N tert-butyl n-cyclopropyl-n-[2-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]carbamate Chemical compound O1C(C)=NC(CCN(C2CC2)C(=O)OC(C)(C)C)=N1 AEEQTSOBTVKZFR-UHFFFAOYSA-N 0.000 description 1
JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 1
229960003766 thrombin (human) Drugs 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
229960004295 valine Drugs 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)
Peptides Or Proteins (AREA)

SK148-93A 1992-03-06 1993-03-01 Process for preparing sulfoamidocarboxamides and their pharmaceutical compositions SK14893A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CH72892		1992-03-06

Publications (1)

Publication Number	Publication Date
SK14893A3 true SK14893A3 (en)	1993-11-10

Family

ID=4193803

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK148-93A SK14893A3 (en)	1992-03-06	1993-03-01	Process for preparing sulfoamidocarboxamides and their pharmaceutical compositions

Country Status (10)

Country	Link
KR (1)	KR100274422B1 (pl)
BR (1)	BR9300753A (pl)
HR (1)	HRP930266A2 (pl)
MX (1)	MX9301155A (pl)
PL (1)	PL173030B1 (pl)
SG (1)	SG48063A1 (pl)
SI (1)	SI9300104A (pl)
SK (1)	SK14893A3 (pl)
YU (1)	YU14493A (pl)
ZA (1)	ZA931403B (pl)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TW201303B (pl) *	1990-07-05	1993-03-01	Hoffmann La Roche

1993
- 1993-02-22 SG SG1996006774A patent/SG48063A1/en unknown
- 1993-02-26 ZA ZA931403A patent/ZA931403B/xx unknown
- 1993-03-01 SK SK148-93A patent/SK14893A3/sk unknown
- 1993-03-02 MX MX9301155A patent/MX9301155A/es unknown
- 1993-03-03 YU YU14493A patent/YU14493A/sh unknown
- 1993-03-04 BR BR9300753A patent/BR9300753A/pt not_active Application Discontinuation
- 1993-03-05 KR KR1019930003315A patent/KR100274422B1/ko not_active Expired - Fee Related
- 1993-03-05 PL PL93297960A patent/PL173030B1/pl unknown
- 1993-03-05 HR HR930266A patent/HRP930266A2/xx not_active Application Discontinuation
- 1993-03-05 SI SI19939300104A patent/SI9300104A/sl unknown

Also Published As

Publication number	Publication date
PL297960A1 (en)	1993-09-20
BR9300753A (pt)	1993-09-08
SG48063A1 (en)	1998-04-17
YU14493A (sh)	1997-01-08
ZA931403B (en)	1993-09-06
MX9301155A (es)	1993-09-01
HRP930266A2 (en)	1996-04-30
KR930019627A (ko)	1993-10-18
KR100274422B1 (ko)	2000-12-15
PL173030B1 (pl)	1998-01-30
SI9300104A (en)	1993-09-30

Publication	Publication Date	Title
US5405854A (en)	1995-04-11	Sulfonamidocarboxamides
US5595999A (en)	1997-01-21	Guanidine derivatives
US5559232A (en)	1996-09-24	Carboxamides
US5707994A (en)	1998-01-13	2,3-diaminopropionic acid derivative
SK145894A3 (en)	1995-09-13	Vinegar acid derivatives, method of their production, pharmaceutical agents on their base and their using
JP3654908B2 (ja)	2005-06-02	Ｎｋ１およびｎｋ２アンタゴニストとしてのアシルアミノアルケニレン―アミド誘導体
KR100274422B1 (ko)	2000-12-15	설폰아미도카복스아미드
FI105474B (fi)	2000-08-31	Välituotteina käytettäviä amiineja ja alkoholeja
HRP930501A2 (en)	1996-04-30	Guanidins