MXPA05000269A

MXPA05000269A - Derivados de 3-guanidinocarbonil-1-heteroaril-indol procedimiento de preparacion, su uso como medicamentos, y composiciones farmaceuticas que los contienen.

Derivados de 3-guanidinocarbonil-1-heteroaril-indol procedimiento de preparacion, su uso como medicamentos, y composiciones farmaceuticas que los contienen.

Info

Publication number: MXPA05000269A
Authority: MX; Mexico
Prior art keywords: indole; quinol; carbon atoms; formula; guanidinocarbonyl
Prior art date: 2002-07-16

Application number

MXPA05000269A

Other languages

English (en)

Spanish (es)

Inventor

Arielle Genevois-Borella

Original Assignee

Aventis Pharma Gmbh

Priority date

2002-07-16

Filing date

2003-07-02

Publication date

2005-03-31

2003-07-02 Application filed by Aventis Pharma Gmbh filed Critical Aventis Pharma Gmbh

2005-03-31 Publication of MXPA05000269A publication Critical patent/MXPA05000269A/es

Links

239000003814 drug Substances 0.000 title claims abstract description 61
239000008194 pharmaceutical composition Substances 0.000 title claims description 9
229940054051 antipsychotic indole derivative Drugs 0.000 title abstract description 4
238000002360 preparation method Methods 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 91
238000011282 treatment Methods 0.000 claims abstract description 33
238000011321 prophylaxis Methods 0.000 claims abstract description 26
206010019280 Heart failures Diseases 0.000 claims abstract description 16
230000006378 damage Effects 0.000 claims abstract description 13
206010002383 Angina Pectoris Diseases 0.000 claims abstract description 5
230000000747 cardiac effect Effects 0.000 claims abstract 4
230000002829 reductive effect Effects 0.000 claims description 128
125000004432 carbon atom Chemical group C* 0.000 claims description 67
150000003839 salts Chemical class 0.000 claims description 65
239000001257 hydrogen Substances 0.000 claims description 57
229910052739 hydrogen Inorganic materials 0.000 claims description 57
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 55
239000000203 mixture Substances 0.000 claims description 48
125000000217 alkyl group Chemical group 0.000 claims description 43
-1 heteroaryl halide Chemical class 0.000 claims description 42
208000035475 disorder Diseases 0.000 claims description 39
229910052736 halogen Inorganic materials 0.000 claims description 33
150000002367 halogens Chemical class 0.000 claims description 32
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 29
239000004480 active ingredient Substances 0.000 claims description 22
229940079593 drug Drugs 0.000 claims description 21
229910052757 nitrogen Inorganic materials 0.000 claims description 21
125000003545 alkoxy group Chemical group 0.000 claims description 18
210000000056 organ Anatomy 0.000 claims description 17
229910052701 rubidium Inorganic materials 0.000 claims description 17
201000010099 disease Diseases 0.000 claims description 16
230000003176 fibrotic effect Effects 0.000 claims description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 13
125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
210000001519 tissue Anatomy 0.000 claims description 11
201000001320 Atherosclerosis Diseases 0.000 claims description 10
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 10
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206010012601 diabetes mellitus Diseases 0.000 claims description 9
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125000000623 heterocyclic group Chemical group 0.000 claims description 9
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
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125000005842 heteroatom Chemical group 0.000 claims description 8
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NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 5
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SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 5
AJNOHOKROJBZCT-UHFFFAOYSA-N n-(diaminomethylidene)-1-quinolin-8-ylindole-3-carboxamide Chemical compound C12=CC=CC=C2C(C(=O)NC(=N)N)=CN1C1=CC=CC2=CC=CN=C12 AJNOHOKROJBZCT-UHFFFAOYSA-N 0.000 claims description 5
210000002307 prostate Anatomy 0.000 claims description 5
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
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HQJBOAGQISFBDF-UHFFFAOYSA-N 5-chloro-n-(diaminomethylidene)-1-quinolin-4-ylindole-3-carboxamide Chemical compound C12=CC=C(Cl)C=C2C(C(=O)NC(=N)N)=CN1C1=CC=NC2=CC=CC=C12 HQJBOAGQISFBDF-UHFFFAOYSA-N 0.000 claims description 4
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QULWGILGNIQETG-UHFFFAOYSA-N n-(diaminomethylidene)-6-fluoro-1-quinolin-4-ylindole-3-carboxamide Chemical compound C12=CC(F)=CC=C2C(C(=O)NC(=N)N)=CN1C1=CC=NC2=CC=CC=C12 QULWGILGNIQETG-UHFFFAOYSA-N 0.000 claims description 4
208000003663 ventricular fibrillation Diseases 0.000 claims description 4
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 3
206010001497 Agitation Diseases 0.000 claims description 3
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QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 3
206010020850 Hyperthyroidism Diseases 0.000 claims description 3
206010020880 Hypertrophy Diseases 0.000 claims description 3
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229910052794 bromium Inorganic materials 0.000 claims description 3
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PUZUCPCNYYLOEI-UHFFFAOYSA-N n-(diaminomethylidene)-1-isoquinolin-1-yl-5-methylindole-3-carboxamide Chemical compound C1=CC=C2C(N3C4=CC=C(C=C4C(C(=O)NC(N)=N)=C3)C)=NC=CC2=C1 PUZUCPCNYYLOEI-UHFFFAOYSA-N 0.000 claims description 3
NFSLAWMOVYHDDJ-UHFFFAOYSA-N n-(diaminomethylidene)-1-isoquinolin-1-ylindole-3-carboxamide Chemical compound C12=CC=CC=C2C(C(=O)NC(=N)N)=CN1C1=NC=CC2=CC=CC=C12 NFSLAWMOVYHDDJ-UHFFFAOYSA-N 0.000 claims description 3
SCCJIRWRRWMGOQ-UHFFFAOYSA-N n-(diaminomethylidene)-1-isoquinolin-3-ylindole-3-carboxamide Chemical compound C12=CC=CC=C2C(C(=O)NC(=N)N)=CN1C1=CC2=CC=CC=C2C=N1 SCCJIRWRRWMGOQ-UHFFFAOYSA-N 0.000 claims description 3
VTTHAQHOQREWQT-UHFFFAOYSA-N n-(diaminomethylidene)-1-quinolin-2-ylindole-3-carboxamide Chemical compound C12=CC=CC=C2C(C(=O)NC(=N)N)=CN1C1=CC=C(C=CC=C2)C2=N1 VTTHAQHOQREWQT-UHFFFAOYSA-N 0.000 claims description 3
PERYWYHLSVIZKE-UHFFFAOYSA-N n-(diaminomethylidene)-1-quinolin-6-ylindole-3-carboxamide Chemical compound C12=CC=CC=C2C(C(=O)NC(=N)N)=CN1C1=CC=C(N=CC=C2)C2=C1 PERYWYHLSVIZKE-UHFFFAOYSA-N 0.000 claims description 3
WZNJJLIOELOVQY-UHFFFAOYSA-N n-(diaminomethylidene)-5-fluoro-1-quinolin-4-ylindole-3-carboxamide Chemical compound C12=CC=C(F)C=C2C(C(=O)NC(=N)N)=CN1C1=CC=NC2=CC=CC=C12 WZNJJLIOELOVQY-UHFFFAOYSA-N 0.000 claims description 3
YKGKPBSWEZNJIL-UHFFFAOYSA-N n-(diaminomethylidene)-5-methyl-1-quinolin-2-ylindole-3-carboxamide Chemical compound C1=CC=CC2=NC(N3C4=CC=C(C=C4C(C(=O)NC(N)=N)=C3)C)=CC=C21 YKGKPBSWEZNJIL-UHFFFAOYSA-N 0.000 claims description 3
NLQPGNNTRRUVIC-UHFFFAOYSA-N n-(diaminomethylidene)-5-methyl-1-quinolin-4-ylindole-3-carboxamide Chemical compound C1=CC=C2C(N3C4=CC=C(C=C4C(C(=O)NC(N)=N)=C3)C)=CC=NC2=C1 NLQPGNNTRRUVIC-UHFFFAOYSA-N 0.000 claims description 3
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IEHPJPLVSZBVRB-UHFFFAOYSA-N 4-chloro-n-(diaminomethylidene)-1-quinolin-4-ylindole-3-carboxamide Chemical compound C12=CC=CC(Cl)=C2C(C(=O)NC(=N)N)=CN1C1=CC=NC2=CC=CC=C12 IEHPJPLVSZBVRB-UHFFFAOYSA-N 0.000 claims description 2
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ZVUKOZCGHXIAOK-UHFFFAOYSA-N n-(diaminomethylidene)-1-quinolin-4-yl-4-(trifluoromethyl)indole-3-carboxamide Chemical compound C12=CC=CC(C(F)(F)F)=C2C(C(=O)NC(=N)N)=CN1C1=CC=NC2=CC=CC=C12 ZVUKOZCGHXIAOK-UHFFFAOYSA-N 0.000 claims description 2
IIWAQGPFZRYANP-UHFFFAOYSA-N n-(diaminomethylidene)-4-fluoro-1-quinolin-4-ylindole-3-carboxamide Chemical compound C12=CC=CC(F)=C2C(C(=O)NC(=N)N)=CN1C1=CC=NC2=CC=CC=C12 IIWAQGPFZRYANP-UHFFFAOYSA-N 0.000 claims description 2
BYLTZQKXPXUHGE-UHFFFAOYSA-N n-(diaminomethylidene)-6-hydroxy-1-quinolin-4-ylindole-3-carboxamide Chemical compound C12=CC(O)=CC=C2C(C(=O)NC(=N)N)=CN1C1=CC=NC2=CC=CC=C12 BYLTZQKXPXUHGE-UHFFFAOYSA-N 0.000 claims description 2
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