ECSP993243A - PROTEASE INHIBITORS VII - Google Patents
PROTEASE INHIBITORS VIIInfo
- Publication number
- ECSP993243A ECSP993243A ECSP993243A ECSP993243A EC SP993243 A ECSP993243 A EC SP993243A EC SP993243 A ECSP993243 A EC SP993243A EC SP993243 A ECSP993243 A EC SP993243A
- Authority
- EC
- Ecuador
- Prior art keywords
- alkyl
- group
- het
- cycloalkyl
- nr2h
- Prior art date
Links
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 abstract 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 11
- 150000001875 compounds Chemical class 0.000 abstract 5
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 2
- 206010065687 Bone loss Diseases 0.000 abstract 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 abstract 2
- 210000000845 cartilage Anatomy 0.000 abstract 2
- 230000015556 catabolic process Effects 0.000 abstract 2
- 238000006731 degradation reaction Methods 0.000 abstract 2
- 102200160920 rs35304565 Human genes 0.000 abstract 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
- 102000004171 Cathepsin K Human genes 0.000 abstract 1
- 108090000625 Cathepsin K Proteins 0.000 abstract 1
- 208000030136 Marchiafava-Bignami Disease Diseases 0.000 abstract 1
- 208000029725 Metabolic bone disease Diseases 0.000 abstract 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 abstract 1
- 101150020251 NR13 gene Proteins 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 208000010191 Osteitis Deformans Diseases 0.000 abstract 1
- 208000001132 Osteoporosis Diseases 0.000 abstract 1
- 208000027868 Paget disease Diseases 0.000 abstract 1
- 102000035195 Peptidases Human genes 0.000 abstract 1
- 108091005804 Peptidases Proteins 0.000 abstract 1
- 239000004365 Protease Substances 0.000 abstract 1
- 206010003246 arthritis Diseases 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000024693 gingival disease Diseases 0.000 abstract 1
- 208000007565 gingivitis Diseases 0.000 abstract 1
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000036210 malignancy Effects 0.000 abstract 1
- 208000027202 mammary Paget disease Diseases 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 201000008482 osteoarthritis Diseases 0.000 abstract 1
- 201000001245 periodontitis Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
El presente invento proporciona compuestos de fórmula I: (gráfico), en la que: A se selecciona entre el grupo que consta de: C(O) y CH(OH); R1 se selecciona entre el grupo que consta de: (gráfico), R2 se selcciona entre el grupo que consta de: H, alquilo C1-6, cicloalquil C3-6 alquilo C0-6 Ar-alquilo C0-6, Het-alquilo C0-6, R9C(O), R9C(S)-, R9SO2-, R9OC(O)-, R9R12NC(O)-, R9R12NC(S)-, R12HNCH(R12)C(O)-, R9OC(O)NR12CH(R12)C(O)-, adamantil-C(O)-, o (gráfico), R¿¿ se selcciona entre el grupo que consta de: H, alquilo C1-6, Ar-alquilo C0-6, y Het-alquilo C0-6; R¿¿¿se selcciona entre el grupo que consta de: H, alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6, y Het-alquilo C0-6; R3 y R8 se seleccionan independientemente entre el grupo que consta de: H, alquenilo C2-6, alquinilo C2-6, Het, Ar o alquilo C1-6 opcionalmente sustituido con OR13 SR13, NR13 2, R13NC(O)OR5, CO2R13, CO2NR13 2, N(C=NH)NH2, Het y Ar; R4 se selcciona entre el grupo que consta de: H, alquilo C1-6, cicloalquil C3-6 alquilo C0-6, Ar-alquilo C0-6, Het-alquilo C0-6, R5C(O), R5C(S)-, R5SO2-, R5OC(O)-, R5R14NC(O)-, R5R14NC(S)-, R14HNCH(R14)C(O)- y R5OC(O)NR14 CH(R14)C(O)-; R5, R9 y R10 se selccionan independientemente entre el grupo que consta de: alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6, y Het-alquilo C0-6; R6 se selecciona entre el grupo que consta de: H, alquilo C1-6 Ar-alquilo C0-6 y Het-alquilo C0-6; R7 se selecciona entre el grupo que consta de: H, alquilo C1-6, ciclolaquil C3-6-alquilo C0-6 Ar-alquilo C0-6, Het-alquilo C0-6 R10C(O)-, R10C(S)-, R10SO2-, R10OC(O)-, R10R15NC(O)-, R10R15NC(S)-, R15HNCH(R15)C(O)- y R10 OC(O)NR15CH(R15)C(O)-: R6 y R7 se concetan para formar un anillo de pirrolidina , piperidina o morfolina; cada R¿se selcciona independientemente entre el grupo que consta de: H, alquilo C1-6 Ar-alquilo C0-6 y Het-alquilo C0-6; R11 es Ar; R12, R13, R14 y R15 se selccionan independientemente entre el grupo que constan de: H, alquilo C1-6, Ar-alquilo C0-6 y Het-alquilo C0-6; R* se selecciona entre el grupo que consta de: H, alquilo C1-6, cicloalquil C3-6-alquilo C0-6, Ar-alquilo C0-6, y Het-alquilo C0-6; Z se selecciona entre el grupo que consta de: C(O) y CH2; M se selecciona entre el grupo que consta de: HC=HC; H2C-CH2; H(OR2)C-C(OR2)H; H(OR2)C-CH2; H(NR2H)C-C(NR2H)H; H(OR2)C-C(NR2H)H; y H(NR2H)C-CH2; X se selecciona entre el grupo que consta de:CH2, S y O n es 1-7; y sus sales framacéuticamente aceptables, hidratos y solvatos, que inhiben a proteasas, inclusive a catepsina K, composiciones farmacéuticas de dichos compuestos, nuevos compuestos intermedios de dichos compuestos, y método spara tratar enfermedades con excesiva pérdida de huesos o degradación de cartílagos o matrices, inclusive osteoporosis; una enfermedad gingival inclusive gingivitis y periodontitis, artritis, más especificamente, osteoartritis y artritis reumatoide; la enfermedad de Paget; hipercalmenia de malignidad y una enfermedad metabólica de los huesos,que comprende inhibir dicha pérdida de huesos o degradación excesiva de cartílagos o de matrices por administración a un paciente que necesita de ello, de un compuesto del presente invento.The present invention provides compounds of formula I: (graph), wherein: A is selected from the group consisting of: C (O) and CH (OH); R1 is selected from the group consisting of: (graph), R2 is selected from the group consisting of: H, C1-6 alkyl, C3-6 cycloalkyl, C0-6 alkyl, Ar-C0-6 alkyl, Het-C0 alkyl -6, R9C (O), R9C (S) -, R9SO2-, R9OC (O) -, R9R12NC (O) -, R9R12NC (S) -, R12HNCH (R12) C (O) -, R9OC (O) NR12CH (R12) C (O) -, adamantyl-C (O) -, or (graph), R¿¿ is selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl, and Het -C0-6-alkyl; R¿¿¿ is selected from the group consisting of: H, C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl, and Het-C0-6 alkyl; R3 and R8 are independently selected from the group consisting of: H, C2-6 alkenyl, C2-6 alkynyl, Het, Ar or C1-6 alkyl optionally substituted with OR13 SR13, NR13 2, R13NC (O) OR5, CO2R13, CO2NR13 2, N (C = NH) NH2, Het and Ar; R4 is selected from the group consisting of: H, C1-6 alkyl, C3-6 cycloalkyl, C0-6 alkyl, Ar-C0-6 alkyl, Het-C0-6 alkyl, R5C (O), R5C (S) - , R5SO2-, R5OC (O) -, R5R14NC (O) -, R5R14NC (S) -, R14HNCH (R14) C (O) - and R5OC (O) NR14 CH (R14) C (O) -; R5, R9 and R10 are independently selected from the group consisting of: C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl, and Het-C0-6 alkyl; R6 is selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R7 is selected from the group consisting of: H, C1-6 alkyl, C3-6 cyclolakyl-C0-6 alkyl Ar-C0-6 alkyl, Het-C0-6 alkyl R10C (O) -, R10C (S) - , R10SO2-, R10OC (O) -, R10R15NC (O) -, R10R15NC (S) -, R15HNCH (R15) C (O) - and R10 OC (O) NR15CH (R15) C (O) -: R6 and R7 they concatenate to form a pyrrolidine, piperidine or morpholine ring; each R is independently selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R11 is Ar; R12, R13, R14 and R15 are independently selected from the group consisting of: H, C1-6 alkyl, Ar-C0-6 alkyl and Het-C0-6 alkyl; R * is selected from the group consisting of: H, C1-6 alkyl, C3-6 cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl, and Het-C0-6 alkyl; Z is selected from the group consisting of: C (O) and CH2; M is selected from the group consisting of: HC = HC; H2C-CH2; H (OR2) C-C (OR2) H; H (OR2) C-CH2; H (NR2H) C-C (NR2H) H; H (OR2) C-C (NR2H) H; and H (NR2H) C-CH2; X is selected from the group consisting of: CH2, S and O n is 1-7; and its pharmaceutically acceptable salts, hydrates and solvates, which inhibit proteases, including cathepsin K, pharmaceutical compositions of said compounds, new intermediate compounds of said compounds, and a method for treating diseases with excessive bone loss or degradation of cartilage or matrices, including osteoporosis; a gingival disease including gingivitis and periodontitis, arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalmenia of malignancy and a metabolic bone disease, comprising inhibiting said bone loss or excessive degradation of cartilage or matrices by administration to a patient in need thereof of a compound of the present invention.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ECSP993243 ECSP993243A (en) | 1999-11-29 | 1999-11-29 | PROTEASE INHIBITORS VII |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ECSP993243 ECSP993243A (en) | 1999-11-29 | 1999-11-29 | PROTEASE INHIBITORS VII |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ECSP993243A true ECSP993243A (en) | 2000-03-22 |
Family
ID=42044232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ECSP993243 ECSP993243A (en) | 1999-11-29 | 1999-11-29 | PROTEASE INHIBITORS VII |
Country Status (1)
| Country | Link |
|---|---|
| EC (1) | ECSP993243A (en) |
-
1999
- 1999-11-29 EC ECSP993243 patent/ECSP993243A/en unknown
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