AR088327A1 - Agentes inductores de la apoptosis para tratar el cancer y las enfermedades inmunes y autoinmunes - Google Patents
Agentes inductores de la apoptosis para tratar el cancer y las enfermedades inmunes y autoinmunesInfo
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- AR088327A1 AR088327A1 ARP120103811A ARP120103811A AR088327A1 AR 088327 A1 AR088327 A1 AR 088327A1 AR P120103811 A ARP120103811 A AR P120103811A AR P120103811 A ARP120103811 A AR P120103811A AR 088327 A1 AR088327 A1 AR 088327A1
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- group
- nhc
- cr6r7
- independently selected
- alkynyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Compuestos que inhiben la actividad de las proteínas antiapoptóticas Bcl-xL, composiciones que contienen dichos compuestos y métodos para tratar enfermedades en las que se expresan las proteínas antiapoptóticas Bcl-xL. Reivindicación 1: Un compuesto caracterizado porque es de la fórmula (1) o una sal aceptable para terapia del mismo, donde X es heteroarilo; donde el heteroarilo representado por X está opcionalmente sustituido con uno, dos, tres, o cuatro R⁴; Y¹ es fenileno o heteroarileno C₅₋₆; opcionalmente fusionado a uno o dos anillos seleccionados entre el grupo que consiste en cicloalcano C₃₋₈, cicloalqueno C₃₋₈, benceno, heteroareno C₅₋₆, heterocicloalcano C₃₋₈, y heterocicloalqueno C₃₋₈; donde Y¹ está opcionalmente sustituido con uno, dos, tres, o cuatro sustituyentes seleccionados en forma independiente entre el grupo que consiste en R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, CO(O)H, C(O)H, OH, CN, N₅, NO₂, F, Cl, Br y I; L¹ se selecciona entre el grupo que consiste en (CR⁶R⁷)q, (CR⁶R⁷)ₛ-O-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-C-(O)-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-S-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-S(O)₂-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-NR⁶AC(O)-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-C(O)NR⁶A-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-NR⁶A-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-S(O)₂NR⁶A-(CR⁶R⁷)ʳ, y (CR⁶R⁷)ₛ-NR⁶AS(O)₂-(CR⁶R⁷)ʳ; Y² es cicloalquilo C₈₋₁₄, cicloalquenilo C₈₋₁₄, heterocicloalquilo C₈₋₁₄, o heterocicloalquenilo C₈₋₁₄; opcionalmente fusionado a uno o dos anillos seleccionados entre el grupo que consiste en cicloalcano C₃₋₈, cicloalqueno C₃₋₈, benceno, heteroareno C₅₋₆, heterocicloalcano C₃₋₈, y heterocicloalqueno C₃₋₈; donde Y² está opcionalmente sustituido con uno, dos, tres, cuatro, o cinco sustituyentes seleccionados en forma independiente entre el grupo que consiste en R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, C(O)R⁸, CO(O)R⁸, OC(O)R⁸, OC(O)OR⁸, NH₂, NHR⁸, N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHS(O)₂R⁸, NR⁸S(O)₂R⁸, NHC(O)OR⁸, NR⁸C(O)OR⁸, NHC(O)NH₂, NHC(O)NHR⁸, NHC(O)N(R⁸)₂, NR⁸C(O)NHR⁸, NR⁸C(O)N(R⁸)₂, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, C(O)NHOH, C(O)NHOR⁸, C(O)NHSO₂R⁸, C(O)NR⁸SO₂R⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, CO(O)H, C(O)H, OH, CN, N₃, NO₂, F, Cl, Br y I; Z¹ se selecciona entre el grupo que consiste en C(O)OR⁹, C(O)NR¹⁰R¹¹, C(O)R¹¹, NR¹⁰C(O)R¹¹, NR¹⁰C(O)NR¹⁰R¹¹, OC(O)NR¹⁰R¹¹, NR¹⁰C(O)OR⁹, C(=NOR¹⁰)NR¹⁰R¹¹, NR¹⁰C(=NCN)NR¹⁰R¹¹, NR¹⁰S(O)₂NR¹⁰R¹¹, S(O)₂R⁹, S(O)₂NR¹⁰R¹¹, N(R¹⁰)S(O)₂R¹¹, NR¹⁰C(=NR¹¹)NR¹⁰R¹¹, C(=S)NR¹⁰R¹¹, C(=NR¹⁰)NR¹⁰R¹¹, halógeno, NO₂, y CN; o Z¹ se selecciona entre el grupo que consiste en el grupo de formulas (2); R¹, en cada caso, se selecciona en forma independiente entre el grupo que consiste en halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆; R², en cada caso, se selecciona en forma independiente entre el grupo que consiste en deuterio, halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆; dos R² que se unen al mismo átomo de carbono, junto con dicho átomo de carbono, forman opcionalmente un anillo seleccionado entre el grupo que consiste en heterocicloalquilo, heterocicloalquenilo, cicloalquilo, y cicloalquenilo; R³, en cada caso, se selecciona en forma independiente entre el grupo que consiste en halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆; R⁴, en cada caso, se selecciona en forma independiente entre el grupo que consiste en NR¹²R¹³, OR¹², CN, NO₂, halógeno, C(O)OR¹², C(O)NR¹²R¹³, NR¹²C(O)R¹³, NR¹²S(O)₂R¹⁴, NR¹²S(O)R¹⁴, S(O)₂R¹⁴, S(O)R¹⁴ y R¹⁴; R⁵, en cada caso, se selecciona en forma independiente entre el grupo que consiste en alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, hidroxialquilo C₁₋₆, arilo, heterociclilo, cicloalquilo, y cicloalquenilo; R⁶A se selecciona en forma independiente entre el grupo que consiste en hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆; R⁶ y R⁷, en cada caso, se seleccionan en forma independiente entre sí entre el grupo que consiste en hidrógeno, R¹⁵, OR¹⁵, SR¹⁵, S(O)R¹⁵, SO₂R¹⁵, C(O)R¹⁵, CO(O)R¹⁵, OC(O)R¹⁵, OC(O)OR¹⁵, NH₂, NHR¹⁵, N(R¹⁵)₂, NHC(O)R¹⁵, NR¹⁵C(O)R¹⁵, NHS(O)₂R¹⁵, NR¹⁵S(O)₂R¹⁵, NHC(O)OR¹⁵, NR¹⁵C(O)OR¹⁵, NHC(O)NH₂, NHC(O)NHR¹⁵, NHC(O)N(R¹⁵)₂, NR¹⁵C(O)NHR¹⁵, NR¹⁵C(O)N(R¹⁵)₂, C(O)NH₂, C(O)NHR¹⁵, C(O)N(R¹⁵)₂, C(O)NHOH, C(O)NHOR¹⁵, C(O)NHSO₂R¹⁵, C(O)NR¹⁵SO₂R¹⁵, SO₂NH₂, SO₂NHR¹⁵, SO₂N(R¹⁵)₂, CO(O)H, C(O)H, OH, CN, N₃, NO₂, F, Cl, Br y I; R⁸, en cada caso, se selecciona en forma independiente entre el grupo que consiste en alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, arilo, heterociclilo, cicloalquilo, y cicloalquenilo; donde R⁸ alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆ están opcionalmente sustituidos con uno, dos, tres, cuatro, cinco, o seis sustituyentes seleccionados en forma independiente entre el grupo que consiste en R¹⁶, OR¹⁶, SR¹⁶, S(O)R¹⁶, SO₂R¹⁶, C(O)R¹⁶, CO(O)R¹⁶, OC(O)R¹⁶, OC(O)OR¹⁶, NH₂, NHR¹⁶, N(R¹⁶)₂, NHC(O)R¹⁶, NR¹⁶C(O)R¹⁶, NHS(O)₂R¹⁶, NR¹⁶S(O)₂R¹⁶, NHC(O)OR¹⁶, NR¹⁶C(O)OR¹⁶, NHC(O)NH₂, NHC(O)NHR¹⁶, NHC(O)N(R¹⁶)₂, NR¹⁶C(O)NHR¹⁶, NR¹⁶C(O)N(R¹⁶)₂, C(O)NH₂, C(O)NHR¹⁶, C(O)N(R¹⁶)₂, C(O)NHOH, C(O)NHOR¹⁶, C(O)NHSO₂R¹⁶, C(O)NR¹⁶SO₂R¹⁶, SO₂NH₂, SO₂NHR¹⁶, SO₂N(R¹⁶)₂, CO(O)H, C(O)H, OH, CN, N₃, NO₂, F, Cl, Br y I; donde R⁸ arilo, heterociclilo, cicloalquilo, y cicloalquenilo están opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados en forma independiente entre el grupo que consiste en alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, NH₂, C(O)NH₂, SO₂NH₂, C(O)H, (O), OH, CN, NO₂, OCF₃, OCF₂CF₃, F, Cl, Br y I; R⁹ se selecciona entre el grupo que consiste en alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, cicloalquilo, fenilo y (CH₂)₁₋₄-fenilo; y R¹⁰ y R¹¹, en cada caso, se seleccionan en forma independiente entre sí entre el grupo que consiste en hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo C₃₋₆, haloalquilo C₁₋₆, fenilo y (CH₂)₁₋₄-fenilo; o R¹⁰ y R¹¹, o R¹⁰ y R⁹, junto con el átomo al cual están unidos se combinan para formar un heterociclilo; Rᵏ, en cada caso, se selecciona en forma independiente entre el grupo que consiste en alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋Ȉ
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161547162P | 2011-10-14 | 2011-10-14 | |
| CN2012079012 | 2012-07-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR088327A1 true AR088327A1 (es) | 2014-05-28 |
Family
ID=47116421
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP120103811A AR088327A1 (es) | 2011-10-14 | 2012-10-12 | Agentes inductores de la apoptosis para tratar el cancer y las enfermedades inmunes y autoinmunes |
Country Status (36)
| Country | Link |
|---|---|
| EP (1) | EP2766361B1 (es) |
| JP (2) | JP6155270B2 (es) |
| KR (1) | KR102019643B1 (es) |
| AR (1) | AR088327A1 (es) |
| AU (2) | AU2012322698A1 (es) |
| BR (1) | BR112014009053B1 (es) |
| CA (1) | CA2851364C (es) |
| CL (1) | CL2014000905A1 (es) |
| CO (1) | CO6950476A2 (es) |
| CR (2) | CR20200097A (es) |
| CY (1) | CY1118224T1 (es) |
| DK (1) | DK2766361T3 (es) |
| DO (2) | DOP2014000070A (es) |
| EC (1) | ECSP14000357A (es) |
| ES (1) | ES2598877T3 (es) |
| GT (1) | GT201400064A (es) |
| HK (1) | HK1200167A1 (es) |
| HR (1) | HRP20161319T1 (es) |
| HU (1) | HUE030589T2 (es) |
| IL (1) | IL231856A (es) |
| LT (1) | LT2766361T (es) |
| ME (1) | ME02514B (es) |
| MX (1) | MX356031B (es) |
| PE (1) | PE20141282A1 (es) |
| PH (1) | PH12015501498A1 (es) |
| PL (1) | PL2766361T3 (es) |
| PT (1) | PT2766361T (es) |
| RS (1) | RS55342B1 (es) |
| RU (1) | RU2625315C2 (es) |
| SG (1) | SG11201401279XA (es) |
| SI (1) | SI2766361T1 (es) |
| TW (1) | TWI571466B (es) |
| UA (1) | UA115042C2 (es) |
| UY (1) | UY34382A (es) |
| WO (1) | WO2013055897A1 (es) |
| ZA (1) | ZA201402556B (es) |
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| EP3229844B1 (en) * | 2014-12-09 | 2020-03-04 | AbbVie Inc. | Antibody drug conjugates with cell permeable bcl-xl inhibitors |
| MX2017007629A (es) * | 2014-12-09 | 2018-05-17 | Abbvie Inc | Compuestos inhibidores de bcl-xl que tienen una baja permeabilidad en las celulas y conjugados de anticuerpo-farmaco que los incluyen. |
| MX2017007637A (es) * | 2014-12-09 | 2017-09-05 | Abbvie Inc | Compuestos inhibidores de bcl-xl y conjugados de anticuerpo-farmaco que los incluyen. |
| CN104473923B (zh) * | 2014-12-29 | 2016-08-17 | 巩春智 | 一种防治慢性心力衰竭的药物组合物及其应用 |
| WO2016131100A1 (en) * | 2015-02-18 | 2016-08-25 | The Walter And Eliza Hall Institute Of Medical Research | Methods of treating infectious diseases |
| US10195213B2 (en) | 2015-03-13 | 2019-02-05 | Unity Biotechnology, Inc. | Chemical entities that kill senescent cells for use in treating age-related disease |
| CN116059201A (zh) * | 2016-06-08 | 2023-05-05 | 艾伯维公司 | 抗egfr抗体药物偶联物 |
| MX2018015280A (es) * | 2016-06-08 | 2019-08-12 | Abbvie Inc | Conjugados de anticuerpo y farmaco anti-egfr. |
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| CN109562169A (zh) * | 2016-06-08 | 2019-04-02 | 艾伯维公司 | 抗cd98抗体及抗体药物偶联物 |
| CN116284404A (zh) | 2016-06-08 | 2023-06-23 | 艾伯维公司 | 抗b7-h3抗体和抗体药物偶联物 |
| MX2018015272A (es) * | 2016-06-08 | 2019-08-12 | Abbvie Inc | Anticuerpos anti-cd98 y conjugados de anticuerpo y farmaco. |
| EP3468615A1 (en) * | 2016-06-08 | 2019-04-17 | AbbVie Inc. | Anti-egfr antibody drug conjugates |
| WO2018092064A1 (en) * | 2016-11-18 | 2018-05-24 | Novartis Ag | Combinations of mdm2 inhibitors and bcl-xl inhibitors |
| WO2019000236A1 (en) * | 2017-06-27 | 2019-01-03 | Merck Sharp & Dohme Corp. | ALLOSTERIC MODULATORS OF 3- (1H-PYRAZOL-4-YL) PYRIDINE FROM THE M4 ACETYLCHOLINE MUSCARINIC RECEPTOR |
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