MXPA06014023A

MXPA06014023A - Terapias combinadas que utilizan inhibidores de benzamida del receptor p2x7.

Terapias combinadas que utilizan inhibidores de benzamida del receptor p2x7.

Info

Publication number: MXPA06014023A
Authority: MX; Mexico
Prior art keywords: hydroxy; alkyl; chloro; benzamide; dihydro
Prior art date: 2004-06-29

Application number

MXPA06014023A

Other languages

English (en)

Spanish (es)

Inventor

James B Chung

Christopher A Gabel

Gail L Jungbluth

Original Assignee

Warner Lambert Co

Priority date

2004-06-29

Filing date

2005-06-16

Publication date

2007-02-08

2005-06-16 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2007-02-08 Publication of MXPA06014023A publication Critical patent/MXPA06014023A/es

Links

102100037602 P2X purinoceptor 7 Human genes 0.000 title abstract description 27
101710189965 P2X purinoceptor 7 Proteins 0.000 title abstract description 27
239000003112 inhibitor Substances 0.000 title abstract description 22
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title abstract description 10
238000002648 combination therapy Methods 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 70
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 claims abstract description 19
102000051628 Interleukin-1 receptor antagonist Human genes 0.000 claims abstract description 18
108700021006 Interleukin-1 receptor antagonist Proteins 0.000 claims abstract description 18
239000003795 chemical substances by application Substances 0.000 claims abstract description 18
UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 claims abstract description 17
229960001940 sulfasalazine Drugs 0.000 claims abstract description 17
NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 claims abstract description 17
206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 15
201000010099 disease Diseases 0.000 claims abstract description 14
HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 claims abstract description 11
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125000000217 alkyl group Chemical group 0.000 claims description 297
150000001875 compounds Chemical class 0.000 claims description 175
-1 hydroxy, amino Chemical group 0.000 claims description 159
125000000753 cycloalkyl group Chemical group 0.000 claims description 96
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 85
229910052736 halogen Inorganic materials 0.000 claims description 69
150000002367 halogens Chemical class 0.000 claims description 68
125000000623 heterocyclic group Chemical group 0.000 claims description 64
229910052757 nitrogen Inorganic materials 0.000 claims description 50
125000003545 alkoxy group Chemical group 0.000 claims description 48
125000003118 aryl group Chemical group 0.000 claims description 47
125000004093 cyano group Chemical group *C#N 0.000 claims description 42
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
150000003839 salts Chemical class 0.000 claims description 39
125000001424 substituent group Chemical group 0.000 claims description 32
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 23
229910052739 hydrogen Inorganic materials 0.000 claims description 20
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125000001072 heteroaryl group Chemical group 0.000 claims description 19
239000008194 pharmaceutical composition Substances 0.000 claims description 19
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239000000651 prodrug Substances 0.000 claims description 18
125000005843 halogen group Chemical group 0.000 claims description 14
239000012453 solvate Substances 0.000 claims description 11
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 10
108090001005 Interleukin-6 Proteins 0.000 claims description 10
FUCKCIVGBCBZNP-UHFFFAOYSA-N 2-chloro-n-[(1-hydroxycycloheptyl)methyl]-5-[4-(2-hydroxy-3-methoxypropyl)-3,5-dioxo-1,2,4-triazin-2-yl]benzamide Chemical compound O=C1N(CC(O)COC)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC2(O)CCCCCC2)=C1 FUCKCIVGBCBZNP-UHFFFAOYSA-N 0.000 claims description 9
XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 9
101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims description 9
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229960005370 atorvastatin Drugs 0.000 claims description 9
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102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 9
239000003757 phosphotransferase inhibitor Substances 0.000 claims description 9
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
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125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
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LMVZQBQXTHCTDI-UHFFFAOYSA-N 2-chloro-5-[4-(2,3-dihydroxypropyl)-3,5-dioxo-1,2,4-triazin-2-yl]-n-[(1-hydroxycyclohexyl)methyl]benzamide Chemical compound O=C1N(CC(O)CO)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC2(O)CCCCC2)=C1 LMVZQBQXTHCTDI-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
150000002829 nitrogen Chemical class 0.000 claims description 3
JMVYKXHUTCCANK-UHFFFAOYSA-N 2-chloro-5-[4-(2,3-dihydroxypropyl)-3,5-dioxo-1,2,4-triazin-2-yl]-n-[(1-hydroxycycloheptyl)methyl]benzamide Chemical compound O=C1N(CC(O)CO)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC2(O)CCCCCC2)=C1 JMVYKXHUTCCANK-UHFFFAOYSA-N 0.000 claims description 2
SKHOFKQIJDWTCL-UHFFFAOYSA-N 2-chloro-5-[4-(2-hydroxy-3-methoxypropyl)-3,5-dioxo-1,2,4-triazin-2-yl]-n-(2-hydroxy-2-phenylethyl)benzamide Chemical compound O=C1N(CC(O)COC)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC(O)C=2C=CC=CC=2)=C1 SKHOFKQIJDWTCL-UHFFFAOYSA-N 0.000 claims description 2
IUPMKDQZZPUSLS-UHFFFAOYSA-N 2-chloro-5-[4-(cyanomethyl)-3,5-dioxo-1,2,4-triazin-2-yl]-n-[(1-hydroxycycloheptyl)methyl]benzamide Chemical compound C=1C(N2C(N(CC#N)C(=O)C=N2)=O)=CC=C(Cl)C=1C(=O)NCC1(O)CCCCCC1 IUPMKDQZZPUSLS-UHFFFAOYSA-N 0.000 claims description 2
RBAADOGLQCDEJX-UHFFFAOYSA-N 2-chloro-n-[(1-hydroxycycloheptyl)methyl]-5-[4-(2-methoxyethyl)-3,5-dioxo-1,2,4-triazin-2-yl]benzamide Chemical compound O=C1N(CCOC)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC2(O)CCCCCC2)=C1 RBAADOGLQCDEJX-UHFFFAOYSA-N 0.000 claims description 2
NAVAMNWMBLWSNC-UHFFFAOYSA-N 2-chloro-n-[(1-hydroxycyclooctyl)methyl]-5-[4-(2-hydroxy-3-methoxypropyl)-3,5-dioxo-1,2,4-triazin-2-yl]benzamide Chemical compound O=C1N(CC(O)COC)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC2(O)CCCCCCC2)=C1 NAVAMNWMBLWSNC-UHFFFAOYSA-N 0.000 claims description 2
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 2
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125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
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KJPZROKEPKPKNY-UHFFFAOYSA-N 2-chloro-5-[3,5-dioxo-4-(3,3,3-trifluoro-2-hydroxypropyl)-1,2,4-triazin-2-yl]-n-[(1-hydroxycycloheptyl)methyl]benzamide Chemical compound O=C1N(CC(O)C(F)(F)F)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC2(O)CCCCCC2)=C1 KJPZROKEPKPKNY-UHFFFAOYSA-N 0.000 claims 1
UTVQECIXWCMQOC-UHFFFAOYSA-N 2-chloro-n-[(1-hydroxycyclohexyl)methyl]-5-[4-(2-hydroxy-3-methoxypropyl)-3,5-dioxo-1,2,4-triazin-2-yl]benzamide Chemical compound O=C1N(CC(O)COC)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC2(O)CCCCC2)=C1 UTVQECIXWCMQOC-UHFFFAOYSA-N 0.000 claims 1
YHXISHVHTWUPKM-UHFFFAOYSA-N 5-[4-(2-amino-2-oxoethyl)-3,5-dioxo-1,2,4-triazin-2-yl]-2-chloro-n-[(1-hydroxycycloheptyl)methyl]benzamide Chemical compound O=C1N(CC(=O)N)C(=O)C=NN1C1=CC=C(Cl)C(C(=O)NCC2(O)CCCCCC2)=C1 YHXISHVHTWUPKM-UHFFFAOYSA-N 0.000 claims 1
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