ES2660146T3 - Sales del inhibidor de cdk - Google Patents

Sales del inhibidor de cdk Download PDF

Info

Publication number
ES2660146T3
ES2660146T3 ES10715240.7T ES10715240T ES2660146T3 ES 2660146 T3 ES2660146 T3 ES 2660146T3 ES 10715240 T ES10715240 T ES 10715240T ES 2660146 T3 ES2660146 T3 ES 2660146T3
Authority
ES
Spain
Prior art keywords
compound
salt
salts
maleate
cdk inhibitor
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES10715240.7T
Other languages
English (en)
Inventor
Massimo Zampieri
Annalisa Airoldi
Maria Gioia Fornaretto
Maria Gabriella Brasca
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nerviano Medical Sciences SRL
Original Assignee
Nerviano Medical Sciences SRL
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nerviano Medical Sciences SRL filed Critical Nerviano Medical Sciences SRL
Application granted granted Critical
Publication of ES2660146T3 publication Critical patent/ES2660146T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Oncology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Communicable Diseases (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Virology (AREA)
  • Hematology (AREA)
  • Transplantation (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Vascular Medicine (AREA)
  • Dermatology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Una sal del compuesto 125 que tiene la fórmula siguiente:**Fórmula** seleccionada de maleato, malonato y glicolato, que comprenden polimorfos e hidratos de estos.

Description

imagen1
imagen2
imagen3
imagen4
propanol) y se convierte en la Forma I o III mediante el efecto de las condiciones de secado o exposición a condiciones de temperatura y humedad acentuadas (por ejemplo, almacenamiento a 40°C/75% de RH).
La Forma III es una forma de cristal de alto punto de fusión de la sal de maleato del compuesto 125 que se caracteriza
5 como una forma hidratada que muestra adsorción reversible de aproximadamente 1 mol de agua en condiciones ambientales (por ejemplo, 25°C/60% de RH). La absorción de aproximadamente 3,0÷3,5% a 25°C y 90% de humedad relativa (RH) es reversible al disminuir la RH a aproximadamente 20% ala misma temperatura.
Como un aspecto adicional, se ha encontrado que la sal de maleato del compuesto 125puede obtenerse como un sólido 10 cristalino en las relaciones molares de 0,5:1, 1:1 y 2:1.
La sal de glicolato del compuesto 125 y la sal de malonato del compuesto 125 son ligeramente higroscópicas, mostrando ambas una absorción de agua reversible de aproximadamente 2,5% a 25°C/90% de RH.
15 Las sales del compuesto 125 muestran buena solubilidad, en particular, la solubilidad de las sales de maleato, malonato y glicolato en una solución de dextrosa al 0,5% es de aproximadamente 10 mg/mL o superior.
Además de la ventaja de exhibir alta solubilidad en agua, las sales del compuesto 125, en particular, las sales de maleato, malonato, glicolato, son también particularmente adecuadas para que se fabriquen reproduciblemente en una 20 relación de ácido/base clara.
Este hallazgo hace que estas sales sean particularmente adecuadas para su uso en las formulaciones líquidas para formulaciones tanto orales, así comointravenosas.
25 Tabla1 -Descripcióndelaspropiedadesdeestadosólidodelassalesyformasdebaselibredel compuesto 125.
30
35
40
45
50
55
60
65
Compuesto 125 Sal (*)
Forma crsitalina Figura PXRD Tabla PXRD Picos significativos PXRD (2zeta, grado) (**) Figura de DSC
Maleato
I 11 7 5,3, 6,0, 11,9, 12,7, 13,5, 14,5, 17,9, 19,4, 20,9, 22,9, 23,2, 24,7 20
Maleato
II 2B, 12 8 4,8, 9,6, 11,6, 15,7, 16,0, 16,7, 19,3, 20,9, 21,3, 22,1, 23,3, 27,7, 17F
Maleato
III 5D, 13 9 6,0, 11,8, 12,3, 13,3, 14,3, 16,3, 17,8, 20,8, 22,8, 24,3, 26,4, 27,6 20
Malonato
I 1E, 7 3 11,5, 12,4, 14,3, 15,8, 18,8, 20,9, 21,8, 22,7, 23,0, 16B
imagen5
imagen6 imagen7 imagen8 24,8 imagen9
Glicolato
I 1D, 6 2 6,6, 11,8, 12,2, 12,7, 16,1, 17,5, 19,4, 21,9, 23,6, 23,9, 25,9, 27,8 17B
Triclorhidrato
I 1B, 4B, 8 4 7,7, 8,2, 10,6, 11,1, 17,6, 22,1, 23,2, 24,4, 25,1, 26,4,28,1,31,9 18A
Diclorhidrato
I 4C, 9 5 7,7, 8,1, 11,0, 22,1, 26,4, 25,1, 31,8, 24,3, 28,1, 10,6, 17,6, 23,0 18B
Clorhidrato
I 4D, 10 6 4,6, 5,2, 5,4, 8,1, 8,4, 9,4, 10,2, 10,6, 14,6, 21,0, 23,5, 24,9 18C
Base libre
I 1A, 2A, 3A, 4A, 14 10 5,6, 9,3, 10,9, 11,4, 14,4, 14,5, 17,3, 19,3, 19,6, 21,8, 22,4, 25,5 16A, 17A
Base libre
II 15 11 6,1, 10,3, 11,4, 11,9, 12,6, 14,5, 18,5, 18,9, 20,3, 23,0, 24,8, 25,7 No disponible
6
imagen10
imagen11
imagen12
imagen13
imagen14
imagen15
imagen16
Tabla 2 -Compuesto 125, sal de glicolato
Posición (grado)
Intensidad (CPS) Intensidad relativa
6, 6
525, 9 16, 5
9, 7
504, 5 15, 8
10, 6
277, 1 8, 7
10, 9
190, 9 6, 0
11, 8
2122, 7 66, 6
12, 2
1133, 9 35, 6
12, 7
852, 3 26, 7
13, 1
130, 6 4, 1
13, 8
74, 4 2, 3
15, 6
122, 5 3, 8
16, 1
525, 5 16, 5
16, 5
516, 8 16, 2
17, 3
198, 8 6, 2
17, 5
720, 2 22, 6
18, 1
86, 9 2, 7
19, 4
3187, 8 100, 0
20, 1
312, 9 9, 8
20, 4
355, 5 11, 2
20, 7
99, 6 3, 1
21, 0
189, 7 6, 0
21, 2
280, 3 8, 8
21, 9
1167, 1 36, 6
22, 5
386, 5 12, 1
22, 8
240, 3 7, 5
23, 6
1620, 6 50, 8
23, 9
1419, 2 44, 5
25, 9
1221, 0 38, 3
27, 8
859, 2 27, 0
28, 3
164, 6 5, 2
29, 2
152, 9 4, 8
30, 3
196, 2 6, 2
30, 7
203, 4 6, 4
31, 1
107, 6 3, 4
32, 5
156, 7 4, 9
33, 1
167, 6 5, 3
14
imagen17
-Compuesto 125, sal de triclorhidrato, Forma I
Posición (grado)
Intensidad (CPS) Intensidad relativa
5, 4
183, 0 11, 1
7, 7
1483, 0 90, 0
8, 2
1642, 0 99, 6
10, 6
245, 7 14, 9
11, 1
1648, 3 100, 0
12, 2
95, 6 5, 8
13, 1
234, 0 14, 2
14, 6
138, 4 8, 4
15, 3
76, 9 4, 7
15, 6
72, 7 4, 4
16, 2
25, 6 1, 6
17, 3
182, 0 11, 0
17, 6
316, 5 19, 2
18, 4
37, 0 2, 3
20, 3
141, 4 8, 6
21, 2
196, 6 11, 9
21, 6
48, 8 3, 0
22, 1
561, 9 34, 1
22, 6
182, 1 11, 1
23, 1
195, 4 11, 9
23, 2
244, 8 14, 9
24, 4
268, 1 16, 3
24, 9
167, 1 10, 1
25, 1
318, 6 19, 3
25, 4
160, 4 9, 7
26, 4
641, 3 38, 9
28, 1
343, 9 20, 9
28, 6
104, 3 6, 3
30, 9
229, 2 13, 9
31, 9
387, 6 23, 5
33, 5
98, 6 6, 0
16
Tabla 5 -Compuesto 125, sal de diclorhidrato
Posición (grado)
Intensidad (CPS) Intensidad relativa
5, 3
236, 3 12, 0
7, 7
1965, 7 100, 0
8, 1
1922, 5 97, 8
10, 6
288, 0 14, 7
11, 0
1694, 4 86, 2
13, 1
263, 9 13, 4
14, 6
210, 1 10, 7
15, 3
77, 1 3, 9
15, 5
107, 8 5, 5
17, 3
139, 2 7, 1
17, 6
279, 9 14, 2
18, 5
56, 2 2, 9
20, 1
47, 1 2, 4
20, 3
175, 7 8, 9
21, 2
185, 8 9, 5
21, 5
115, 8 5, 9
22, 1
545, 4 27, 8
22, 6
233, 9 11, 9
23, 0
270, 8 13, 8
23, 2
240, 9 12, 3
23, 4
91, 7 4, 7
24, 3
312, 2 15, 9
24, 9
200, 5 10, 2
25, 1
523, 9 26, 7
25, 4
209, 4 10, 7
26, 4
526, 5 26, 8
27, 2
83, 2 4, 2
28, 1
296, 7 15, 1
28, 5
169, 9 8, 6
30, 8
258, 4 13, 1
31, 8
445, 9 22, 7
33, 5
155, 1 7, 9
17
Tabla 6 -Compuesto 125, sal de clorhidrato
imagen18
Posición (grado)
Intensidad (CPS) Intensidad relativa
4, 6
191, 7 53, 9
5, 2
201, 1 56, 6
5, 4
172, 8 48, 6
7, 6
49, 7 14, 0
8, 1
355, 4 100, 0
8, 4
111, 5 31, 4
9, 4
112, 8 31, 7
10, 2
115, 5 32, 5
10, 6
176, 1 49, 5
11, 1
73, 5 20, 7
12, 0
23, 8 6, 7
12, 4
70, 4 19, 8
13, 5
76, 4 21, 5
13, 8
59, 7 16, 8
14, 0
74, 2 20, 9
14, 6
110, 4 31, 1
14, 8
45, 2 12, 7
16, 7
20, 2 5, 7
17, 0
40, 7 11, 5
17, 5
51, 5 14, 5
18, 7
43, 6 12, 3
19, 2
41, 4 11, 7
20, 1
44, 4 12, 5
21, 0
151, 9 42, 7
23, 5
159, 6 44, 9
24, 0
36, 4 10, 3
24, 9
221, 1 62, 2
26, 2
69, 6 19, 6
26, 9
32, 9 9, 3
27, 9
37, 3 10, 5
28, 4
26, 1 7, 3
18
imagen19
imagen20
Tabla 9 -Compuesto 125, sal demaleato FormaIII
imagen21
Posición (grado)
Intensidad (CPS) Intensidad relativa
5, 1
222, 0 9, 1
6, 0
441, 1 18, 1
8, 3
68, 2 2, 8
9, 3
43, 0 1, 8
10, 0
79, 3 3, 3
11, 2
246, 4 10, 1
11, 8
280, 8 11, 5
12, 3
373, 9 15, 3
13, 3
543, 8 22, 3
14, 3
414, 3 17, 0
14, 7
60, 2 2, 5
15, 9
204, 0 8, 4
16, 3
520, 7 21, 3
16, 9
126, 6 5, 2
17, 8
668, 4 27, 4
18, 2
173, 2 7, 1
19, 4
255, 3 10, 5
19, 8
250, 7 10, 3
20, 2
223, 7 9, 2
20, 8
773, 5 31, 7
21, 8
144, 8 5, 9
22, 8
2442, 6 100, 0
23, 7
271, 2 11, 1
24, 3
275, 9 11, 3
24, 7
81, 4 3, 3
24, 9
204, 9 8, 4
25, 9
115, 9 4, 7
26, 4
390, 9 16, 0
27, 6
333, 8 13, 7
28, 1
140, 8 5, 8
31, 1
85, 5 3, 5
32, 0
73, 8 3, 0
21
imagen22
imagen23
22
imagen24
imagen25
imagen26

Claims (1)

  1. imagen1
ES10715240.7T 2009-04-29 2010-04-23 Sales del inhibidor de cdk Active ES2660146T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP09159030 2009-04-29
EP09159030 2009-04-29
PCT/EP2010/055463 WO2010125004A1 (en) 2009-04-29 2010-04-23 Cdk inhibitor salts

Publications (1)

Publication Number Publication Date
ES2660146T3 true ES2660146T3 (es) 2018-03-21

Family

ID=42199163

Family Applications (1)

Application Number Title Priority Date Filing Date
ES10715240.7T Active ES2660146T3 (es) 2009-04-29 2010-04-23 Sales del inhibidor de cdk

Country Status (8)

Country Link
US (1) US8586598B2 (es)
EP (1) EP2424868B1 (es)
JP (1) JP5801285B2 (es)
CN (1) CN102428086B (es)
AR (1) AR076433A1 (es)
ES (1) ES2660146T3 (es)
TW (1) TW201043631A (es)
WO (1) WO2010125004A1 (es)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8916577B2 (en) * 2011-01-26 2014-12-23 Nerviano Medical Sciences S.R.L. Tricyclic derivatives, process for their preparation and their use as kinase inhibitors
RU2591191C2 (ru) * 2011-01-26 2016-07-10 НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. Трициклические пирроло производные, способ их получения и их применение в качестве ингибиторов киназы
HRP20190564T1 (hr) 2013-10-18 2019-05-17 University Health Network Sol i kristalni oblici inhibitora plk-4
DK3129374T3 (en) 2014-04-07 2019-04-08 Netherlands Translational Res Center B V (5,6-dihydro) pyrimido [4,5-e] INDOLIZINER
JP7038675B2 (ja) * 2016-03-11 2022-03-18 ステルス バイオセラピューティクス インコーポレイテッド 結晶塩形態
CN107216340B (zh) * 2016-03-22 2021-05-04 中国科学院上海药物研究所 一种dppiv抑制剂的盐型及其制备方法
CN107216339B (zh) * 2016-03-22 2021-05-04 中国科学院上海药物研究所 一种dppiv抑制剂马来酸盐的多晶型及其制备方法
US11034724B2 (en) 2017-04-05 2021-06-15 Stealth Biotherapeutics Corp. Crystalline salt forms of Boc-D-Arg-DMT-Lys-(Boc)-Phe-NH2
US10676506B2 (en) 2018-01-26 2020-06-09 Stealth Biotherapeutics Corp. Crystalline bis- and tris-hydrochloride salt of elamipretide
CN110092775B (zh) * 2018-01-29 2021-09-10 轩竹生物科技有限公司 靶向cdk4/6激酶抑制剂的晶型
KR102531772B1 (ko) * 2018-01-29 2023-05-11 수안주 바이오파마슈티컬 컴퍼니 리미티드 Cdk4/6 키나아제 억제제를 타겟팅하는 결정형
CN109632555B (zh) * 2018-12-28 2021-07-27 上海新黄河制药有限公司 一种富马酸福莫特罗无定型含量的动态蒸汽吸附分析方法
EP3959209A4 (en) 2019-04-24 2022-12-28 University Health Network S4 CRYSTALLINE FORM OF A PLK4 INHIBITOR (1R,2S)-(E)-2-(3-(4-((CIS-2,6-DIMETHYLMORPHOLINO)METHYL)STYRYL)-1H-IMIDAZOL-6-YL )-5'-METHOXYSPIRO[CYCLOPROPANE-L,3'-INDOLIN]-2'-ONE FUMARATE
CN112010839B (zh) * 2019-05-31 2022-06-17 轩竹生物科技股份有限公司 靶向丝/苏氨酸激酶抑制剂的晶型
EP3797776B1 (en) * 2019-09-30 2025-07-23 Universitätsmedizin Mainz Cdk4/6 inhibitors for the treatment of psoriasis
CN121712509A (zh) 2023-05-04 2026-03-20 锐新医药公司 用于ras相关疾病或病症的组合疗法
US20250049810A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
IL327306A (en) 2023-10-12 2026-05-01 Revolution Medicines Inc Macrocyclic RAS inhibitors
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025217307A1 (en) 2024-04-09 2025-10-16 Revolution Medicines, Inc. Methods for predicting response to a ras(on) inhibitor and combination therapies
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer
WO2026090116A2 (en) 2024-10-21 2026-04-30 Revolution Medicines, Inc. Ras inhibitors
WO2026090245A1 (en) 2024-10-22 2026-04-30 Revolution Medicines, Inc. Use of ras inhibitors for treating cancer
US20260108528A1 (en) 2024-10-22 2026-04-23 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030100594A1 (en) * 2001-08-10 2003-05-29 Pharmacia Corporation Carbonic anhydrase inhibitor
EA010904B1 (ru) * 2003-05-22 2008-12-30 НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. Производные пиразолохиназолина: способ получения и применение в качестве ингибиторов киназ
EA014231B1 (ru) * 2006-02-10 2010-10-29 НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. Комбинации, включающие ингибитор cdk и антитело фактора роста или антимитотик
EP2019101A1 (en) * 2007-07-26 2009-01-28 GPC Biotech AG Pyrazol[3,4-d]pyrimidin-4-one useful as Kinase Inhibitor
MX2010003269A (es) * 2007-09-25 2010-08-02 Bayer Healthcare Llc Derivados de pirrolotriazina utiles para tratar cancer a traves de la inhibicion de la aurora quinasa.
US8022216B2 (en) * 2007-10-17 2011-09-20 Wyeth Llc Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof
US8518930B2 (en) * 2008-07-29 2013-08-27 Nerviano Medical Sciences S.R.L. Therapeutic combination comprising a CDKS inhibitor and an antineoplastic agent
WO2010012733A1 (en) * 2008-07-29 2010-02-04 Nerviano Medical Sciences S.R.L. Use of a cdk inhibitor for the treatment of glioma
WO2010058006A1 (en) * 2008-11-24 2010-05-27 Nerviano Medical Sciences S.R.L. Cdk inhibitor for the treatment of mesothelioma
US8580793B2 (en) * 2009-03-20 2013-11-12 Nerviano Medical Services S.R.L. Use of kinase inhibitor for the treatment of thymoma

Also Published As

Publication number Publication date
JP2012525345A (ja) 2012-10-22
AR076433A1 (es) 2011-06-08
US20120041007A1 (en) 2012-02-16
CN102428086B (zh) 2014-08-20
HK1169408A1 (en) 2013-01-25
WO2010125004A1 (en) 2010-11-04
EP2424868A1 (en) 2012-03-07
EP2424868B1 (en) 2018-01-10
TW201043631A (en) 2010-12-16
CN102428086A (zh) 2012-04-25
US8586598B2 (en) 2013-11-19
JP5801285B2 (ja) 2015-10-28

Similar Documents

Publication Publication Date Title
ES2519446T3 (es) Proceso para la preparación de ácido 4-amino-butírico sustituido con biarilo o derivados del mismo y su uso en la producción de inhibidores de NEP
RU2397168C2 (ru) Производные тиофена в качестве ингибиторов снк 1
ES2524971T3 (es) Proceso para fabricación y resolución de ácido 2-acilamino-3- difenilpropanoico
AR078151A1 (es) Conjugados de acidos grasos y niacina, composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento de enfermedades metabolicas.
AR059349A1 (es) Sal especifica, forma hidratada y cristalina de un derivado de dihidropteridiona
ES2806458T3 (es) Un procedimiento para producir enzalutamida
AR063351A1 (es) DERIVADOS DE PURINA Y DE PIRIMIDINAS CONDENSADAS, COMPOSICION Y SU USO EN LA PREPARACIoN DE UN MEDICAMENTO PARA INHIBIR EL HSP90 EN UNA CELULA.
AR072199A1 (es) Derivados de fenilimidazol como inhibidores de la enzima pde10a
CU23713B7 (es) Cristales anhidros que incluyen una sal del ácido málico de una 2-indolinona sustituida con 3-pirrol, métodos de preparación y composiciones que las contienen
AR076433A1 (es) Sales inhibidoras de cdk
PE20141050A1 (es) Inhibidores de quinasa relacionados con pirrolo (2,3-d) pirimidina tropomiosina
KR930016389A (ko) No 신타제 및 시클로옥시게나제의 이중 억제제, 이들의 제조방법 및 이들을 함유하는 치료 조성물
JP2005526011A5 (es)
AR044856A1 (es) Acidos biariloximetilarenocarboxilicos; procedimientos para su preparacion; composiciones farmaceuticas que los contienen y su uso en la fabricacion de medicamentos.
AR072261A1 (es) Derivados piperazin-pirazolicos, composiciones farmaceuticas que los contienen y usos de los mismos como agentes anticancerigenos.
ES2450999T3 (es) Método para producir un derivado de aminotiazol y un intermedio de producción
PE20061490A1 (es) Derivados de ciclohexanosulfonilo como inhibidores del transportador de glicina glyt1
ES2933504T3 (es) Sal farmacéuticamente aceptable de alquilcarbamoil naftaleniloxi octenoil hidroxiamida o de sus derivados y método para preparar la misma
AR079497A1 (es) Derivados fenilimidazol que comprenden un enlazante de etinileno como inhibidores de enzima pde10a
AR049401A1 (es) Aza-biciclononanos
ES2366500T3 (es) Ácido (6s)-n(5)-metil-5,6,7,8-tetrahidrofólico cristalino estable, su preparación y uso.
AR037096A1 (es) Compuestos de benzimidazol sustituido,composicion farmacologica que los comprende y uso de los mismos para la preparacion de una droga
ES2543804T3 (es) Polimorfo B de Ibandronato
EA200801960A1 (ru) Соли дулоксетина
AR037698A1 (es) N-[4-(1h-imidazol-1-il)-2-fluorofenil]-3-(trifluorometil)-1h-pirazol-5-carboxamidas como inhibidores del factor xa