IL102138A

IL102138A - Sulfonamides, their preparation and pharmaceutical preparations containing sulfonamides

Sulfonamides, their preparation and pharmaceutical preparations containing sulfonamides

Info

Publication number: IL102138A
Authority: IL; Israel
Prior art keywords: methoxy; butyl; phenoxy; tert; pyrimidin
Prior art date: 1991-06-13

Application number

IL10213892A

Other languages

English (en)

Hebrew (he)

Other versions

IL102138A0 (en

Original Assignee

Hoffmann La Roche

Priority date

1991-06-13

Filing date

1992-06-09

Publication date

1996-09-12

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25687870&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL102138(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1992-06-09 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1993-01-14 Publication of IL102138A0 publication Critical patent/IL102138A0/xx

1996-09-12 Publication of IL102138A publication Critical patent/IL102138A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 3
150000003456 sulfonamides Chemical class 0.000 title abstract description 8
238000002360 preparation method Methods 0.000 title description 9
239000000543 intermediate Substances 0.000 title description 4
229940124530 sulfonamide Drugs 0.000 claims abstract description 20
150000003839 salts Chemical class 0.000 claims abstract description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
208000035475 disorder Diseases 0.000 claims abstract description 10
238000011282 treatment Methods 0.000 claims abstract description 9
206010020772 Hypertension Diseases 0.000 claims abstract description 5
208000028867 ischemia Diseases 0.000 claims abstract description 5
206010002383 Angina Pectoris Diseases 0.000 claims abstract description 4
239000000126 substance Substances 0.000 claims abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 106
150000001875 compounds Chemical class 0.000 claims description 101
-1 methylenedioxy Chemical group 0.000 claims description 82
239000001257 hydrogen Substances 0.000 claims description 57
229910052739 hydrogen Inorganic materials 0.000 claims description 57
150000002431 hydrogen Chemical class 0.000 claims description 40
229910052736 halogen Inorganic materials 0.000 claims description 33
150000002367 halogens Chemical class 0.000 claims description 33
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 32
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
102000002045 Endothelin Human genes 0.000 claims description 10
108050009340 Endothelin Proteins 0.000 claims description 10
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 9
238000000034 method Methods 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
125000001769 aryl amino group Chemical group 0.000 claims description 5
125000005110 aryl thio group Chemical group 0.000 claims description 5
125000004104 aryloxy group Chemical group 0.000 claims description 5
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
230000000694 effects Effects 0.000 claims description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 4
229910052701 rubidium Inorganic materials 0.000 claims description 4
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
HXIYCKAAQPHZBM-UHFFFAOYSA-N 3-methyl-1,2-oxazole-5-carboxylic acid Chemical compound CC=1C=C(C(O)=O)ON=1 HXIYCKAAQPHZBM-UHFFFAOYSA-N 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
229910052783 alkali metal Inorganic materials 0.000 claims description 3
150000001340 alkali metals Chemical class 0.000 claims description 3
150000001450 anions Chemical class 0.000 claims description 3
239000000969 carrier Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
SSZLBBTUZKTYAT-UHFFFAOYSA-N 2-ethyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound CCC1=CC=CC=C1S(=O)(=O)NC1=NC(C)=NC(OCCO)=C1OC1=CC=CC=C1OC SSZLBBTUZKTYAT-UHFFFAOYSA-N 0.000 claims description 2
ZBPVZZIHQFWIIJ-UHFFFAOYSA-N 4-(2,2-dimethylpropyl)-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(CC(C)(C)C)C=C1 ZBPVZZIHQFWIIJ-UHFFFAOYSA-N 0.000 claims description 2
HGCNVBFWQCYTTB-UHFFFAOYSA-N 4-tert-butyl-n-[2-(furan-2-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2OC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HGCNVBFWQCYTTB-UHFFFAOYSA-N 0.000 claims description 2
JRYSTBVLGFETLC-UHFFFAOYSA-N 4-tert-butyl-n-[2-(furan-3-yl)-6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=COC=C2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 JRYSTBVLGFETLC-UHFFFAOYSA-N 0.000 claims description 2
OLQQNLDLUWGUOC-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-2-ethyl-6-(2-methylsulfinylethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C=1C(OC)=CC=C(Cl)C=1OC=1C(OCCS(C)=O)=NC(CC)=NC=1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OLQQNLDLUWGUOC-UHFFFAOYSA-N 0.000 claims description 2
FUYIWALKTPDJRC-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(C)=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCO)=C1 FUYIWALKTPDJRC-UHFFFAOYSA-N 0.000 claims description 2
SPORGDTWHZWWFO-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chlorophenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)NC1=NC=NC(OCCO)=C1OC1=CC=CC=C1Cl SPORGDTWHZWWFO-UHFFFAOYSA-N 0.000 claims description 2
XNZPXOFWYQMBNC-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-ethoxyphenoxy)-6-(2-hydroxyethoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound CCOC1=CC=CC=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XNZPXOFWYQMBNC-UHFFFAOYSA-N 0.000 claims description 2
XRCMKXQGFCYJRK-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-2-[2-(2-hydroxyethoxy)ethyl]-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(CCOCCO)=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 XRCMKXQGFCYJRK-UHFFFAOYSA-N 0.000 claims description 2
IPSKDUSDAACTJJ-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-2-[2-(2-hydroxyethoxy)ethyl]-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC(OC=2C(=NC(CCOCCO)=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCO)=C1 IPSKDUSDAACTJJ-UHFFFAOYSA-N 0.000 claims description 2
LIARTULJNMGSNS-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-2-methyl-5-(2-methylsulfanylphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound CSC1=CC=CC=C1OC(C(=NC(C)=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 LIARTULJNMGSNS-UHFFFAOYSA-N 0.000 claims description 2
WEUUDVAKLXYINL-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(1-oxidopyridin-1-ium-4-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C[N+]([O-])=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 WEUUDVAKLXYINL-UHFFFAOYSA-N 0.000 claims description 2
CSHBWFOWZFSIDZ-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyridin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 CSHBWFOWZFSIDZ-UHFFFAOYSA-N 0.000 claims description 2
ICGLTOLBTVCGPB-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyridin-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=NC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 ICGLTOLBTVCGPB-UHFFFAOYSA-N 0.000 claims description 2
HEBWMVUSTSZAMZ-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyridin-4-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=CN=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HEBWMVUSTSZAMZ-UHFFFAOYSA-N 0.000 claims description 2
DQGJBNBZQJTIHE-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2SC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 DQGJBNBZQJTIHE-UHFFFAOYSA-N 0.000 claims description 2
NFEWKJNARXIISE-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-thiophen-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=CSC=C2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 NFEWKJNARXIISE-UHFFFAOYSA-N 0.000 claims description 2
KPJXDJRWFUDSEA-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 KPJXDJRWFUDSEA-UHFFFAOYSA-N 0.000 claims description 2
MBDSOEMOPHGXEG-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methylphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound CC1=CC=CC=C1OC(C(=NC=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 MBDSOEMOPHGXEG-UHFFFAOYSA-N 0.000 claims description 2
FCJLEBQUOPUDCV-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC(OC=2C(=NC(=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)C=2N=CC=CN=2)OCCO)=C1 FCJLEBQUOPUDCV-UHFFFAOYSA-N 0.000 claims description 2
ZNXOKLWCOWOECF-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCO)=C1 ZNXOKLWCOWOECF-UHFFFAOYSA-N 0.000 claims description 2
DAQDYBGMTAIPFL-GOSISDBHSA-N 4-tert-butyl-n-[6-[(2r)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(C)=N1)OC[C@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 DAQDYBGMTAIPFL-GOSISDBHSA-N 0.000 claims description 2
JANQEUYONJBENB-HXUWFJFHSA-N 4-tert-butyl-n-[6-[(2r)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-thiophen-3-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=CSC=C2)OC[C@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 JANQEUYONJBENB-HXUWFJFHSA-N 0.000 claims description 2
HCAJUXSCGLHBQN-FQEVSTJZSA-N 4-tert-butyl-n-[6-[(2s)-2,3-dihydroxypropoxy]-2-(furan-3-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C2=COC=C2)OC[C@@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HCAJUXSCGLHBQN-FQEVSTJZSA-N 0.000 claims description 2
BDFRYTNUXQDOHF-IBGZPJMESA-N 4-tert-butyl-n-[6-[(2s)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-thiophen-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2SC=CC=2)OC[C@@H](O)CO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 BDFRYTNUXQDOHF-IBGZPJMESA-N 0.000 claims description 2
SHEIXBFGSRILDU-UHFFFAOYSA-N ClC1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=C(C=CC(=C1)F)OC)OCCO Chemical compound ClC1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=C(C=CC(=C1)F)OC)OCCO SHEIXBFGSRILDU-UHFFFAOYSA-N 0.000 claims description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
239000005977 Ethylene Substances 0.000 claims description 2
206010047163 Vasospasm Diseases 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
FMEXEIWSIXFMHL-UHFFFAOYSA-N ethyl 2-[5-[[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]sulfamoyl]-2-methoxyphenoxy]acetate Chemical compound C1=C(OC)C(OCC(=O)OCC)=CC(S(=O)(=O)NC=2C(=C(OCCO)N=CN=2)OC=2C(=CC=CC=2)OC)=C1 FMEXEIWSIXFMHL-UHFFFAOYSA-N 0.000 claims description 2
125000004494 ethyl ester group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
ZHYADMKRGVVLCQ-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=CC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=C1 ZHYADMKRGVVLCQ-UHFFFAOYSA-N 0.000 claims description 2
HJQRNFPSYLHLAX-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-propylpyrimidin-4-yl]-4-propan-2-ylbenzenesulfonamide Chemical compound C=1C=CC=C(OC)C=1OC=1C(OCCO)=NC(CCC)=NC=1NS(=O)(=O)C1=CC=C(C(C)C)C=C1 HJQRNFPSYLHLAX-UHFFFAOYSA-N 0.000 claims description 2
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 claims 5
150000001408 amides Chemical class 0.000 claims 4
KVUJNXSGZHFSBB-UHFFFAOYSA-N 2-ethyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxy-4-methylphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound CCC1=CC=CC=C1S(=O)(=O)NC1=NC=NC(OCCO)=C1OC1=CC=C(C)C=C1OC KVUJNXSGZHFSBB-UHFFFAOYSA-N 0.000 claims 1
DUKFXEPSTLLSTI-UHFFFAOYSA-N 4-chloro-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(C)=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(Cl)C=C1 DUKFXEPSTLLSTI-UHFFFAOYSA-N 0.000 claims 1
TXJQLDNVVFRPGL-UHFFFAOYSA-N 4-tert-butyl-n-[5-(4-fluoro-2-methoxyphenoxy)-6-(2-hydroxyethoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC(F)=CC=C1OC(C(=NC(C)=N1)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 TXJQLDNVVFRPGL-UHFFFAOYSA-N 0.000 claims 1
YTBGKHFJEQITFY-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(1-oxidopyridin-1-ium-2-yl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2[N+](=CC=CC=2)[O-])OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 YTBGKHFJEQITFY-UHFFFAOYSA-N 0.000 claims 1
HVRDENHNEUGHGW-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=CC=CC=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 HVRDENHNEUGHGW-UHFFFAOYSA-N 0.000 claims 1
VRFTVVXDJRJGNL-UHFFFAOYSA-N 4-tert-butyl-n-[6-(2-hydroxyethoxy)-5-(3-methoxy-4-methylphenoxy)pyrimidin-4-yl]benzenesulfonamide Chemical compound C1=C(C)C(OC)=CC(OC=2C(=NC=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OCCO)=C1 VRFTVVXDJRJGNL-UHFFFAOYSA-N 0.000 claims 1
DRIHNVYRUGBDHI-QFIPXVFZSA-N 4-tert-butyl-n-[6-[(2s)-2,3-dihydroxypropoxy]-5-(2-methoxyphenoxy)-2-(4-methoxyphenyl)pyrimidin-4-yl]benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1C(N=C1OC[C@@H](O)CO)=NC(NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1OC1=CC=CC=C1OC DRIHNVYRUGBDHI-QFIPXVFZSA-N 0.000 claims 1
101150052863 THY1 gene Proteins 0.000 claims 1
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TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
DFWRZHZPJJAJMX-UHFFFAOYSA-N propanimidamide;hydrochloride Chemical compound Cl.CCC(N)=N DFWRZHZPJJAJMX-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
GMHCEDDZKAYPLB-UHFFFAOYSA-N pyridine-2-carboximidamide;hydrochloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=N1 GMHCEDDZKAYPLB-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
LZIYBABLVXXFGZ-UHFFFAOYSA-N pyrimidine-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=NC=CC=N1 LZIYBABLVXXFGZ-UHFFFAOYSA-N 0.000 description 1
150000008512 pyrimidinediones Chemical class 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
230000035939 shock Effects 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229940023144 sodium glycolate Drugs 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
GQFIWFPBDXSASA-UHFFFAOYSA-M sodium;2-chlorophenolate Chemical compound [Na+].[O-]C1=CC=CC=C1Cl GQFIWFPBDXSASA-UHFFFAOYSA-M 0.000 description 1
ONFAAMBUOAGWSG-UHFFFAOYSA-M sodium;2-methylphenolate Chemical compound [Na+].CC1=CC=CC=C1[O-] ONFAAMBUOAGWSG-UHFFFAOYSA-M 0.000 description 1
IIHZUISTNNNXQQ-UHFFFAOYSA-M sodium;3-methoxyphenolate Chemical compound [Na+].COC1=CC=CC([O-])=C1 IIHZUISTNNNXQQ-UHFFFAOYSA-M 0.000 description 1
MYMOTVMHKLYQCM-UHFFFAOYSA-M sodium;4-methoxyphenolate Chemical compound [Na+].COC1=CC=C([O-])C=C1 MYMOTVMHKLYQCM-UHFFFAOYSA-M 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
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239000003826 tablet Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
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 description 1
YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
IDELNEDBPWKHGK-UHFFFAOYSA-N thiobutabarbital Chemical compound CCC(C)C1(CC)C(=O)NC(=S)NC1=O IDELNEDBPWKHGK-UHFFFAOYSA-N 0.000 description 1
229940026152 thiobutabarbital Drugs 0.000 description 1
URAGJMBGNVOIJC-UHFFFAOYSA-N thiophene-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=CS1 URAGJMBGNVOIJC-UHFFFAOYSA-N 0.000 description 1
CAUZIIYPBLBRFI-UHFFFAOYSA-N thiophene-3-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C=1C=CSC=1 CAUZIIYPBLBRFI-UHFFFAOYSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
230000002792 vascular Effects 0.000 description 1
ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000011706 wistar kyoto rat Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1