AR095249A2 - PROTEASOME INHIBITORS AND THE SAME USE - Google Patents
PROTEASOME INHIBITORS AND THE SAME USEInfo
- Publication number
- AR095249A2 AR095249A2 ARP140100859A ARP140100859A AR095249A2 AR 095249 A2 AR095249 A2 AR 095249A2 AR P140100859 A ARP140100859 A AR P140100859A AR P140100859 A ARP140100859 A AR P140100859A AR 095249 A2 AR095249 A2 AR 095249A2
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- optionally substituted
- alkynyl
- alkenyl
- aryl
- Prior art date
Links
Abstract
Compuestos de ácido borónico, ésteres borónicos, y composiciones de los mismos que pueden modular la apoptosis por ejemplo por inhibición de la actividad de los proteasomas. Los compuestos y composiciones se pueden usar en los métodos que inducen la apoptosis y en el tratamiento de enfermedades como el cáncer y otros trastornos asociados en forma directa o indirecta con la actividad de los proteasomas. Reivindicación 1: Un compuesto la fórmula (1), o una sal farmacéuticamente aceptable, estereoisomérica o tautomérica de ella, caracterizado porque: R¹ es alquilo C₁₋₈, alquenilo C₂₋₈, alquinilo C₂₋₈, o cicloalquilo C₃₋₇; R² es H; Q es -B(OH)₂, -B(OR¹⁴)₂, o un éster borónico cíclico en donde dicho éster borónico cíclico contiene entre 2 y 20 átomos de carbono, y, opcionalmente, un heteroátomo que puede ser N, S, ó O; R¹⁴ es H, alquilo C₁₋₄, cicloalquilo, cicloalquilalquilo, arilo, o aralquilo; X es RAC(=O)-, RANHC(=O)-, RAS(=O)₂-, RAOC(=O)-, RASC(=O)-, o RA; RA es alquilo C₁₋₂₀ opcionalmente sustituido con R²⁰; alquenilo C₂₋₂₀ opcionalmente sustituido con R²⁰; alquinilo C₂₋₂₀ opcionalmente sustituido con R²⁰; carbociclilo opcionalmente sustituido con 1 - 5 R²¹; o heterocarbociclilo opcionalmente sustituido con 1 - 5 R²¹; R²⁰ se selecciona del grupo formado por: -OR²⁰ᵃ, -SR²⁰ᵃ, -S(=O)R²⁰ᵃ, -S(=O)₂R²⁰ᵃ, -S(=O)₂-NHR²⁰ᵃ, -SC(=O)R²⁰ᵃ, -C(=O)R²⁰ᵃ, -C(=O)NHR²⁰ᵃ, -C(=O)O-R²⁰ᵃ, ftalimido, -(O-alquil)ʳ, -O-alquil-OH, -(O-alquil)ʳ-OH, -OR²⁰ᶜ, -SR²⁰ᶜ, -O-alquil-R²⁰ᶜ, -S-alquil-R²⁰ᶜ, -S(=O)-R²⁰ᶜ, -S(=O)₂-R²⁰ᶜ, -S(=O)₂-NHR²⁰ᶜ, -SC(=O)R²⁰ᶜ, -C(=O)R²⁰ᶜ, -C(=O)OR²⁰ᶜ, -C(=O)NHR²⁰ᶜ, carbociclilo opcionalmente sustituido con 1 - 5 R²²; y heterocarbociclilo opcionalmente sustituido con 1 - 5 R²²; R²⁰ᵃ es alquilo C₁₋₂₀, alquenilo C₂₋₂₀, o alquinilo C₂₋₂₀; en donde dicho alquilo, alquenilo, o alquinilo está opcionalmente sustituido con uno o más halo, alquilo C₁₋₄, arilo, heteroarilo o -NHR²⁰ᵇ; R²⁰ᶜ es carbociclilo opcionalmente substituido con 1 - 5 R²²; heterocarbociclilo opcionalmente substituido con 1 - 5 R²²; R²² se selecciona del grupo formado por: alquilo C₁₋₁₀, alquenilo C₂₋₁₀, alquinilo C₂₋₁₀, fenilo, halo, haloalquilo, alcoxi, tioalcoxi, amino, alquilamino, dialquilamino, carboxilo, alquil-OC(=O)-, alquil-C(=O)-, aril-OC(=O)-, alquil-OC(=O)NH-, aril-OC(=O)NH-, alquil-C(=O)NH-, alquil-C(=O)O-, -(alquil-O)ʳ-alquilo, HO-(alquil-O)ʳ-alquil-, -OH, -SH, - CN, -N₃, -CNO, -CNS, alquil-S(=O)-, alquil-S(=O)₂-, H₂NS(=O)-, y H₂NS(=O)₂-; y r es 2, 3, 4, 5, 6, 7, 8, 9, ó 10.Compounds of boronic acid, boronic esters, and compositions thereof that can modulate apoptosis for example by inhibiting proteasome activity. The compounds and compositions can be used in methods that induce apoptosis and in the treatment of diseases such as cancer and other disorders directly or indirectly associated with the activity of proteasomes. Claim 1: A compound of the formula (1), or a pharmaceutically acceptable, stereoisomeric or tautomeric salt thereof, characterized in that: R¹ is C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, or C₃₋₇ cycloalkyl; R² is H; Q is -B (OH) ₂, -B (OR¹⁴) ₂, or a cyclic boronic ester wherein said cyclic boronic ester contains between 2 and 20 carbon atoms, and, optionally, a heteroatom that can be N, S, or OR; R¹⁴ is H, C₁₋₄ alkyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl; X is RAC (= O) -, RANHC (= O) -, RAS (= O) ₂-, RAOC (= O) -, RASC (= O) -, or RA; RA is C₁₋₂₀ alkyl optionally substituted with R²⁰; C₂₋₂₀ alkenyl optionally substituted with R²⁰; C₂₋₂₀ alkynyl optionally substituted with R²⁰; carbocyclyl optionally substituted with 1-5 R²¹; or heterocarbocyclyl optionally substituted with 1-5 R²¹; R²⁰ is selected from the group consisting of: -OR²⁰ᵃ, -SR²⁰ᵃ, -S (= O) R²⁰ᵃ, -S (= O) ₂R²⁰ᵃ, -S (= O) ₂-NHR²⁰ᵃ, -SC (= O) R²⁰ᵃ, -C (= O) R²⁰ᵃ, -C (= O) NHR²⁰ᵃ, -C (= O) O-R²⁰ᵃ, phthalimido, - (O-alkyl) ʳ, -O-alkyl-OH, - (O-alkyl) ʳ-OH , -OR²⁰ᶜ, -SR²⁰ᶜ, -O-alkyl-R²⁰ᶜ, -S-alkyl-R²⁰ᶜ, -S (= O) -R²⁰ᶜ, -S (= O) ₂-R²⁰ᶜ, -S (= O) ₂-NHR²⁰ᶜ, -SC (= O) R²⁰ᶜ, -C (= O) R²⁰ᶜ, -C (= O) OR²⁰ᶜ, -C (= O) NHR²⁰ᶜ, carbocyclyl optionally substituted with 1 - 5 R²²; and heterocarbocyclyl optionally substituted with 1-5 R²²; R²⁰ᵃ is C₁₋₂₀ alkyl, C₂₋₂₀ alkenyl, or C₂₋₂₀ alkynyl; wherein said alkyl, alkenyl, or alkynyl is optionally substituted with one or more halo, C₁₋₄ alkyl, aryl, heteroaryl or -NHR²⁰ᵇ; R²⁰ᶜ is carbocyclyl optionally substituted with 1-5 R²²; heterocarbocyclyl optionally substituted with 1-5 R²²; R²² is selected from the group consisting of: C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, phenyl, halo, haloalkyl, alkoxy, thioalkoxy, amino, alkylamino, dialkylamino, carboxyl, OC-alkyl (= O) -, alkyl-C (= O) -, aryl-OC (= O) -, alkyl-OC (= O) NH-, aryl-OC (= O) NH-, alkyl-C (= O) NH-, alkyl- C (= O) O-, - (alkyl-O) ʳ-alkyl, HO- (alkyl-O) ʳ-alkyl-, -OH, -SH, - CN, -N₃, -CNO, -CNS, alkyl- S (= O) -, alkyl-S (= O) ₂-, H₂NS (= O) -, and H₂NS (= O) ₂-; and r is 2, 3, 4, 5, 6, 7, 8, 9, or 10.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49576403P | 2003-08-14 | 2003-08-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR095249A2 true AR095249A2 (en) | 2015-09-30 |
Family
ID=37426112
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP040102935 AR045381A1 (en) | 2003-08-14 | 2004-08-17 | PROTEASOME INHIBITORS AND METHODS OF THE SAME USE |
| ARP140100859A AR095249A2 (en) | 2003-08-14 | 2014-03-11 | PROTEASOME INHIBITORS AND THE SAME USE |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP040102935 AR045381A1 (en) | 2003-08-14 | 2004-08-17 | PROTEASOME INHIBITORS AND METHODS OF THE SAME USE |
Country Status (7)
| Country | Link |
|---|---|
| CN (1) | CN1867572B (en) |
| AR (2) | AR045381A1 (en) |
| MY (1) | MY162518A (en) |
| PE (1) | PE20050360A1 (en) |
| TW (1) | TWI345465B (en) |
| UA (1) | UA88771C2 (en) |
| ZA (1) | ZA200601293B (en) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA028622B1 (en) * | 2007-08-06 | 2017-12-29 | Милленниум Фармасьютикалз, Инк. | Proteasome inhibitors |
| CN105837608B (en) * | 2007-08-06 | 2018-06-08 | 米伦纽姆医药公司 | Proteasome inhibitor and combinations thereof and purposes |
| CN102961387B (en) * | 2007-08-06 | 2016-04-27 | 米伦纽姆医药公司 | Proteasome inhibitor |
| SI2318419T1 (en) * | 2008-06-17 | 2015-07-31 | Millennium Pharmaceuticals, Inc. | Boronate ester compounds and pharmaceutical compositions thereof |
| CN101638414B (en) * | 2008-07-30 | 2014-01-08 | 江苏先声药物研究有限公司 | Peptidyl boronic acid, ester compound thereof, preparation method of peptidyl boronic acid and ester compound thereof, and use of peptidyl boronic acid and ester compound thereof |
| AR075090A1 (en) * | 2008-09-29 | 2011-03-09 | Millennium Pharm Inc | ACID DERIVATIVES 1-AMINO-2-CYCLLOBUTILETILBORONICO PROTEOSOMA INHIBITORS, USEFUL AS ANTI-BANKER AGENTS, AND PHARMACEUTICAL COMPOSITIONS THAT UNDERSTAND THEM. |
| CN101747354B (en) * | 2008-12-04 | 2014-08-13 | 江苏先声药物研究有限公司 | Dipeptide boronic acids consisting of beta amino acids, ester compounds and preparation methods and uses thereof |
| WO2011087822A1 (en) * | 2009-12-22 | 2011-07-21 | Cephalon, Inc. | Proteasome inhibitors and processes for their preparation, purification and use |
| RU2012146101A (en) * | 2010-03-31 | 2014-05-10 | Милленниум Фармасьютикалз, Инк. | 1-AMINO-2-CYCLOPROPYLETHYL BORONIC ACID DERIVATIVES |
| AU2015327345B9 (en) * | 2014-10-01 | 2020-06-18 | Merck Patent Gmbh | Boronic acid derivatives |
| CN106588965A (en) * | 2015-10-15 | 2017-04-26 | 北京大学 | Urea peptidomimetic boric acid compound as well as pharmaceutical composition, preparation method and application thereof |
| CN107400142B (en) * | 2016-05-19 | 2019-11-19 | 成都奥璟生物科技有限公司 | A kind of boric acid and boric acid ester compound and its application |
| SI3571208T1 (en) * | 2017-01-18 | 2021-06-30 | Principia Biopharma Inc. | Immunoproteasome inhibitors |
| TW201831191A (en) * | 2017-01-23 | 2018-09-01 | 大陸商成都奥璟生物科技有限公司 | Novel boric acid derivative and pharmaceutical composition using same |
| CN114437119A (en) * | 2020-10-30 | 2022-05-06 | 苏州开拓药业股份有限公司 | C-Myc protein inhibitor and preparation method and application thereof |
-
2004
- 2004-08-13 MY MYPI20043299A patent/MY162518A/en unknown
- 2004-08-13 TW TW93124291A patent/TWI345465B/en active
- 2004-08-13 CN CN2004800301520A patent/CN1867572B/en active Active
- 2004-08-13 PE PE2004000784A patent/PE20050360A1/en active IP Right Grant
- 2004-08-13 UA UAA200602694A patent/UA88771C2/en unknown
- 2004-08-17 AR ARP040102935 patent/AR045381A1/en not_active Application Discontinuation
-
2006
- 2006-02-13 ZA ZA200601293A patent/ZA200601293B/en unknown
-
2014
- 2014-03-11 AR ARP140100859A patent/AR095249A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| MY162518A (en) | 2017-06-15 |
| PE20050360A1 (en) | 2005-06-10 |
| UA88771C2 (en) | 2009-11-25 |
| ZA200601293B (en) | 2009-09-30 |
| CN1867572B (en) | 2012-03-28 |
| CN1867572A (en) | 2006-11-22 |
| TW200529810A (en) | 2005-09-16 |
| TWI345465B (en) | 2011-07-21 |
| AR045381A1 (en) | 2005-10-26 |
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| FC | Refusal |