NZ506507A

NZ506507A - Heteroaryl amidine, methylamidine or guanidine derivatives useful as urokinase inhibitors

Heteroaryl amidine, methylamidine or guanidine derivatives useful as urokinase inhibitors

Info

Publication number: NZ506507A
Authority: NZ; New Zealand
Prior art keywords: thiazol; carboxamidine; methylthiothiophene; phenyl; amino
Prior art date: 1998-02-09

Application number

NZ506507A

Other languages

English (en)

Inventor

Carl R Illig

Nalin L Subasinghe

James B Hoffman

Kenneth J Wilson

M Jonathan Rudloph

Original Assignee

Dimensional Pharm Inc

Priority date

1998-02-09

Filing date

1999-02-09

Publication date

2003-08-29

1999-02-09 Application filed by Dimensional Pharm Inc filed Critical Dimensional Pharm Inc

2003-08-29 Publication of NZ506507A publication Critical patent/NZ506507A/en

Links

-1 Heteroaryl amidine Chemical class 0.000 title claims abstract description 443
239000002797 plasminogen activator inhibitor Substances 0.000 title description 9
150000002357 guanidines Chemical class 0.000 title description 7
229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 211
125000000217 alkyl group Chemical group 0.000 claims abstract description 148
239000001257 hydrogen Substances 0.000 claims abstract description 92
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 92
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 73
125000003545 alkoxy group Chemical group 0.000 claims abstract description 65
125000003118 aryl group Chemical group 0.000 claims abstract description 62
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 56
150000002431 hydrogen Chemical group 0.000 claims abstract description 51
229910052736 halogen Inorganic materials 0.000 claims abstract description 48
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 47
150000003839 salts Chemical class 0.000 claims abstract description 42
150000002367 halogens Chemical group 0.000 claims abstract description 39
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 38
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 35
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 29
125000000266 alpha-aminoacyl group Chemical group 0.000 claims abstract description 25
125000004682 aminothiocarbonyl group Chemical group NC(=S)* 0.000 claims abstract description 25
125000005110 aryl thio group Chemical group 0.000 claims abstract description 25
125000004104 aryloxy group Chemical group 0.000 claims abstract description 25
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 25
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 24
239000012453 solvate Substances 0.000 claims abstract description 23
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 20
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 20
206010028980 Neoplasm Diseases 0.000 claims abstract description 17
125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 17
125000004670 alkyl amino thio carbonyl group Chemical group 0.000 claims abstract description 15
125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
206010027476 Metastases Diseases 0.000 claims abstract description 11
125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 11
230000009401 metastasis Effects 0.000 claims abstract description 11
206010060862 Prostate cancer Diseases 0.000 claims abstract description 9
125000002252 acyl group Chemical group 0.000 claims abstract description 9
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims abstract description 8
208000004403 Prostatic Hyperplasia Diseases 0.000 claims abstract description 8
201000004681 Psoriasis Diseases 0.000 claims abstract description 8
125000000304 alkynyl group Chemical group 0.000 claims abstract description 8
125000004659 aryl alkyl thio group Chemical group 0.000 claims abstract description 8
208000037803 restenosis Diseases 0.000 claims abstract description 8
206010014561 Emphysema Diseases 0.000 claims abstract description 7
125000006501 nitrophenyl group Chemical group 0.000 claims abstract description 7
125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 7
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 5
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims abstract description 4
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 4
206010033645 Pancreatitis Diseases 0.000 claims abstract description 4
206010063837 Reperfusion injury Diseases 0.000 claims abstract description 4
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims abstract description 4
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims abstract description 4
201000000028 adult respiratory distress syndrome Diseases 0.000 claims abstract description 4
125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 4
125000003441 thioacyl group Chemical group 0.000 claims abstract description 4
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 3
208000018737 Parkinson disease Diseases 0.000 claims abstract description 3
125000005100 aryl amino carbonyl group Chemical group 0.000 claims abstract description 3
230000009826 neoplastic cell growth Effects 0.000 claims abstract description 3
230000029663 wound healing Effects 0.000 claims abstract description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 14
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 188
235000011468 Albizia julibrissin Nutrition 0.000 claims description 116
241001070944 Mimosa Species 0.000 claims description 116
230000015572 biosynthetic process Effects 0.000 claims description 103
239000007787 solid Substances 0.000 claims description 66
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
238000010992 reflux Methods 0.000 claims description 57
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 54
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 47
125000003282 alkyl amino group Chemical group 0.000 claims description 46
238000000034 method Methods 0.000 claims description 44
239000000203 mixture Substances 0.000 claims description 35
108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 32
150000002148 esters Chemical class 0.000 claims description 32
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
125000001424 substituent group Chemical group 0.000 claims description 31
239000003814 drug Substances 0.000 claims description 30
229960005356 urokinase Drugs 0.000 claims description 27
102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 26
238000003756 stirring Methods 0.000 claims description 26
125000000335 thiazolyl group Chemical group 0.000 claims description 26
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
125000004442 acylamino group Chemical group 0.000 claims description 23
235000019270 ammonium chloride Nutrition 0.000 claims description 23
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
229910052757 nitrogen Inorganic materials 0.000 claims description 22
239000000725 suspension Substances 0.000 claims description 22
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 21
102000035195 Peptidases Human genes 0.000 claims description 20
108091005804 Peptidases Proteins 0.000 claims description 20
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 20
125000001544 thienyl group Chemical group 0.000 claims description 20
125000004663 dialkyl amino group Chemical group 0.000 claims description 19
125000002971 oxazolyl group Chemical group 0.000 claims description 19
QSELGEUCFNFITD-UHFFFAOYSA-N thiophene-2-carboximidamide Chemical compound NC(=N)C1=CC=CS1 QSELGEUCFNFITD-UHFFFAOYSA-N 0.000 claims description 19
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 18
125000004076 pyridyl group Chemical group 0.000 claims description 18
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 18
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 17
125000005843 halogen group Chemical group 0.000 claims description 17
125000005195 alkyl amino carbonyloxy group Chemical group 0.000 claims description 16
125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 16
125000001769 aryl amino group Chemical group 0.000 claims description 16
201000010099 disease Diseases 0.000 claims description 16
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
108010088842 Fibrinolysin Proteins 0.000 claims description 14
239000004365 Protease Substances 0.000 claims description 14
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 14
125000001072 heteroaryl group Chemical group 0.000 claims description 14
125000002883 imidazolyl group Chemical group 0.000 claims description 14
229940012957 plasmin Drugs 0.000 claims description 14
125000005162 aryl oxy carbonyl amino group Chemical group 0.000 claims description 13
125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 13
125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 12
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
239000008194 pharmaceutical composition Substances 0.000 claims description 11
230000017854 proteolysis Effects 0.000 claims description 11
125000003831 tetrazolyl group Chemical group 0.000 claims description 11
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
239000007789 gas Substances 0.000 claims description 10
125000000842 isoxazolyl group Chemical group 0.000 claims description 10
125000001624 naphthyl group Chemical group 0.000 claims description 10
230000008569 process Effects 0.000 claims description 10
LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 claims description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
108090000617 Cathepsin G Proteins 0.000 claims description 9
239000002841 Lewis acid Substances 0.000 claims description 9
230000033115 angiogenesis Effects 0.000 claims description 9
125000005202 dialkylaminocarbonyloxy group Chemical group 0.000 claims description 9
230000002401 inhibitory effect Effects 0.000 claims description 9
150000007517 lewis acids Chemical class 0.000 claims description 9
125000003226 pyrazolyl group Chemical group 0.000 claims description 9
108090000317 Chymotrypsin Proteins 0.000 claims description 8
108090000190 Thrombin Proteins 0.000 claims description 8
229960002376 chymotrypsin Drugs 0.000 claims description 8
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
125000002541 furyl group Chemical group 0.000 claims description 8
210000000265 leukocyte Anatomy 0.000 claims description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 7
108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 7
108010067372 Pancreatic elastase Proteins 0.000 claims description 7
102000016387 Pancreatic elastase Human genes 0.000 claims description 7
210000002744 extracellular matrix Anatomy 0.000 claims description 7
238000010438 heat treatment Methods 0.000 claims description 7
125000001786 isothiazolyl group Chemical group 0.000 claims description 7
125000005968 oxazolinyl group Chemical group 0.000 claims description 7
239000000651 prodrug Substances 0.000 claims description 7
229940002612 prodrug Drugs 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
229960004072 thrombin Drugs 0.000 claims description 7
OMMIMDGHTTXEFT-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(N=2)C=2C=CC(Cl)=CC=2)=C1SC OMMIMDGHTTXEFT-UHFFFAOYSA-N 0.000 claims description 6
108010074860 Factor Xa Proteins 0.000 claims description 6
108090000631 Trypsin Proteins 0.000 claims description 6
102000004142 Trypsin Human genes 0.000 claims description 6
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 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
201000011510 cancer Diseases 0.000 claims description 6
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 6
125000004671 dialkylaminothiocarbonyl group Chemical group 0.000 claims description 6
125000003373 pyrazinyl group Chemical group 0.000 claims description 6
239000012588 trypsin Substances 0.000 claims description 6
102100033174 Neutrophil elastase Human genes 0.000 claims description 5
206010038923 Retinopathy Diseases 0.000 claims description 5
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 5
230000001419 dependent effect Effects 0.000 claims description 5
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 5
125000002769 thiazolinyl group Chemical group 0.000 claims description 5
229960001322 trypsin Drugs 0.000 claims description 5
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 4
WHGZPVSQCGFYBQ-UHFFFAOYSA-N 4-[4-(2,4-dichlorophenyl)-1,3-thiazol-2-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(N=2)C=2C(=CC(Cl)=CC=2)Cl)=C1SC WHGZPVSQCGFYBQ-UHFFFAOYSA-N 0.000 claims description 4
GARVNVZOSLSGOA-UHFFFAOYSA-N 4-[4-(2-chloropyridin-3-yl)-1,3-thiazol-2-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(N=2)C=2C(=NC=CC=2)Cl)=C1SC GARVNVZOSLSGOA-UHFFFAOYSA-N 0.000 claims description 4
KLVFDMVKNCAXRG-UHFFFAOYSA-N 4-[4-(3-hydroxyphenyl)-1,3-thiazol-2-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(N=2)C=2C=C(O)C=CC=2)=C1SC KLVFDMVKNCAXRG-UHFFFAOYSA-N 0.000 claims description 4
UZGWXXYKZGJHJY-UHFFFAOYSA-N 5-methylsulfanyl-4-(4-methyl-1,3-thiazol-2-yl)thiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(C)N=2)=C1SC UZGWXXYKZGJHJY-UHFFFAOYSA-N 0.000 claims description 4
CKYREKXNBZFCFF-UHFFFAOYSA-N 5-methylsulfanyl-4-(4-naphthalen-2-yl-1,3-thiazol-2-yl)thiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(N=2)C=2C=C3C=CC=CC3=CC=2)=C1SC CKYREKXNBZFCFF-UHFFFAOYSA-N 0.000 claims description 4
NPTFSUUZGYDTPV-UHFFFAOYSA-N 5-methylsulfanyl-4-phenylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2C=CC=CC=2)=C1SC NPTFSUUZGYDTPV-UHFFFAOYSA-N 0.000 claims description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
108010073385 Fibrin Proteins 0.000 claims description 4
102000009123 Fibrin Human genes 0.000 claims description 4
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 4
201000005569 Gout Diseases 0.000 claims description 4
206010061218 Inflammation Diseases 0.000 claims description 4
108010028275 Leukocyte Elastase Proteins 0.000 claims description 4
125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 4
125000003368 amide group Chemical group 0.000 claims description 4
206010003246 arthritis Diseases 0.000 claims description 4
239000012298 atmosphere Substances 0.000 claims description 4
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
239000004305 biphenyl Substances 0.000 claims description 4
235000010290 biphenyl Nutrition 0.000 claims description 4
230000010261 cell growth Effects 0.000 claims description 4
125000000068 chlorophenyl group Chemical group 0.000 claims description 4
125000004188 dichlorophenyl group Chemical group 0.000 claims description 4
125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 4
229950003499 fibrin Drugs 0.000 claims description 4
238000009472 formulation Methods 0.000 claims description 4
125000001188 haloalkyl group Chemical group 0.000 claims description 4
125000004464 hydroxyphenyl group Chemical group 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
230000004054 inflammatory process Effects 0.000 claims description 4
125000002757 morpholinyl group Chemical group 0.000 claims description 4
SVVUBLUORZHCSW-UHFFFAOYSA-N n'-amino-5-methylsulfanyl-4-(4-phenyl-1,3-thiazol-2-yl)thiophene-2-carboximidamide Chemical compound S1C(C(=N)NN)=CC(C=2SC=C(N=2)C=2C=CC=CC=2)=C1SC SVVUBLUORZHCSW-UHFFFAOYSA-N 0.000 claims description 4
125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 claims description 4
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 3
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
HNTSNHYPGXXIFN-UHFFFAOYSA-N 4-[2-(2,3-dichloroanilino)-1,3-thiazol-4-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2N=C(NC=3C(=C(Cl)C=CC=3)Cl)SC=2)=C1SC HNTSNHYPGXXIFN-UHFFFAOYSA-N 0.000 claims description 3
ZUWAYNCFFNVIBJ-UHFFFAOYSA-N 4-[2-(2-fluoroanilino)-1,3-thiazol-4-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2N=C(NC=3C(=CC=CC=3)F)SC=2)=C1SC ZUWAYNCFFNVIBJ-UHFFFAOYSA-N 0.000 claims description 3
LIRPGSNQMOFUBQ-UHFFFAOYSA-N 4-[2-(3-chloro-2-methylanilino)-1,3-thiazol-4-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2N=C(NC=3C(=C(Cl)C=CC=3)C)SC=2)=C1SC LIRPGSNQMOFUBQ-UHFFFAOYSA-N 0.000 claims description 3
FDRDCAYYXVHESU-UHFFFAOYSA-N 4-[2-(3-methoxyanilino)-1,3-thiazol-4-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound COC1=CC=CC(NC=2SC=C(N=2)C2=C(SC(=C2)C(N)=N)SC)=C1 FDRDCAYYXVHESU-UHFFFAOYSA-N 0.000 claims description 3
KSJUFIPSZGIVLF-UHFFFAOYSA-N 4-[2-(4-chloro-2-methylanilino)-1,3-thiazol-4-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2N=C(NC=3C(=CC(Cl)=CC=3)C)SC=2)=C1SC KSJUFIPSZGIVLF-UHFFFAOYSA-N 0.000 claims description 3
QJRTVZFPEDJWOS-UHFFFAOYSA-N 4-[2-(4-methoxyanilino)-1,3-thiazol-4-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound C1=CC(OC)=CC=C1NC1=NC(C2=C(SC(=C2)C(N)=N)SC)=CS1 QJRTVZFPEDJWOS-UHFFFAOYSA-N 0.000 claims description 3
ABEISAYFSWNEFB-UHFFFAOYSA-N 4-[2-(benzhydrylamino)-1,3-thiazol-4-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2N=C(NC(C=3C=CC=CC=3)C=3C=CC=CC=3)SC=2)=C1SC ABEISAYFSWNEFB-UHFFFAOYSA-N 0.000 claims description 3
IQHIAMAAHJGYDK-UHFFFAOYSA-N 4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-thiazol-2-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(N=2)C=2C=C3OCCOC3=CC=2)=C1SC IQHIAMAAHJGYDK-UHFFFAOYSA-N 0.000 claims description 3
HFUGBKCICWUZIJ-UHFFFAOYSA-N 4-[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound COC1=CC=CC(C=2N=C(SC=2)C2=C(SC(=C2)C(N)=N)SC)=C1 HFUGBKCICWUZIJ-UHFFFAOYSA-N 0.000 claims description 3
QCNAOMPLQHHHTO-UHFFFAOYSA-N 4-[4-(4-chloro-3-methylphenyl)-1,3-thiazol-2-yl]-5-methylsulfanylthiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(N=2)C=2C=C(C)C(Cl)=CC=2)=C1SC QCNAOMPLQHHHTO-UHFFFAOYSA-N 0.000 claims description 3
IOEIVKCJGQEFIB-UHFFFAOYSA-N 4-phenyl-5-(trifluoromethyl)thiophene-2-carboximidamide Chemical compound S1C(C(=N)N)=CC(C=2C=CC=CC=2)=C1C(F)(F)F IOEIVKCJGQEFIB-UHFFFAOYSA-N 0.000 claims description 3
CABMYWJUHPNDIO-UHFFFAOYSA-N 5-methylsulfanyl-4-(3-phenylphenyl)thiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2C=C(C=CC=2)C=2C=CC=CC=2)=C1SC CABMYWJUHPNDIO-UHFFFAOYSA-N 0.000 claims description 3
QJBLOXHRGXCQHF-UHFFFAOYSA-N 5-methylsulfanyl-4-(6-phenylpyridin-2-yl)thiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2N=C(C=CC=2)C=2C=CC=CC=2)=C1SC QJBLOXHRGXCQHF-UHFFFAOYSA-N 0.000 claims description 3
YCMAPLMAEQZHAF-UHFFFAOYSA-N 5-methylsulfanyl-4-[2-(2,4,5-trimethylanilino)-1,3-thiazol-4-yl]thiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2N=C(NC=3C(=CC(C)=C(C)C=3)C)SC=2)=C1SC YCMAPLMAEQZHAF-UHFFFAOYSA-N 0.000 claims description 3
WWYYVQSACHTSIU-UHFFFAOYSA-N 5-methylsulfanyl-4-[2-(3-phenylpropylamino)-1,3-thiazol-4-yl]thiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2N=C(NCCCC=3C=CC=CC=3)SC=2)=C1SC WWYYVQSACHTSIU-UHFFFAOYSA-N 0.000 claims description 3
IHVADESBZZCEJN-UHFFFAOYSA-N 5-methylsulfanyl-4-[4-(4-nitrophenyl)-1,3-thiazol-2-yl]thiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(N=2)C=2C=CC(=CC=2)[N+]([O-])=O)=C1SC IHVADESBZZCEJN-UHFFFAOYSA-N 0.000 claims description 3
KIZDZRZBUJMDDA-UHFFFAOYSA-N 5-methylsulfanyl-4-[4-(phenylsulfanylmethyl)-1,3-thiazol-2-yl]thiophene-2-carboximidamide Chemical compound S1C(C(N)=N)=CC(C=2SC=C(CSC=3C=CC=CC=3)N=2)=C1SC KIZDZRZBUJMDDA-UHFFFAOYSA-N 0.000 claims description 3
108090000107 Acrosin Proteins 0.000 claims description 3
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108010065822 urokinase inhibitor Proteins 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
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230000003612 virological effect Effects 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
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