公开(公告)号：US12226405B2

公开(公告)日：2025-02-18

申请号：US17241981

申请日：2021-04-27

Applicant: Novartis AG

Inventor： Robin Alec Fairhurst ,  Christine Fritsch ,  Marc Gerspacher ,  Jürgen Hans-Hermann Hinrichs ,  Jean-Baptiste Georges Armand Langlois ,  Catherine Leblanc ,  Tengfei Li ,  Edwige Liliane Jeanne Lorthiois ,  Christophe Mura ,  Cristina Montserrat Nieto-Oberhuber ,  Milen Todorov ,  Andrea Vaupel ,  Nicolas Warin ,  Rainer Wilcken

IPC: A61K31/437 ,  A61K31/155 ,  A61K31/436 ,  A61K31/4375 ,  A61K31/4747 ,  A61K31/519 ,  A61K31/53 ,  A61K31/5377 ,  A61K31/635 ,  A61K31/675 ,  A61P35/00 ,  C07D471/10 ,  C07D471/20 ,  C07D491/20 ,  C07D491/22 ,  C07D495/20 ,  C07D495/22

Abstract: The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt form thereof, wherein the substituents are as defined in the specification; to intermediates in the preparation of the compounds, to pharmaceutical compositions comprising the compounds and to the use of the compounds in the treatment of disease.

公开(公告)号：US10434092B2

公开(公告)日：2019-10-08

申请号：US15719636

申请日：2017-09-29

Applicant: Novartis AG

Inventor： Emmanuelle di Tomaso ,  Marie-Caroline Germa ,  Cristian Massacesi ,  Christine Fritsch ,  Christian René Schnell ,  Ranjana Tavorath

IPC: A61K31/4439 ,  A61K9/00

Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

公开(公告)号：US20180078540A1

公开(公告)日：2018-03-22

申请号：US15719636

申请日：2017-09-29

Applicant: Novartis AG

Inventor： Emmanuelle di Tomaso ,  Marie-Caroline Germa ,  Cristian Massacesi ,  Christine Fritsch ,  Christian René Schnell ,  Ranjana Tavorath

IPC: A61K31/4439 ,  A61K9/00

CPC classification number: A61K31/4439 ,  A61K9/0053

Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

公开(公告)号：US20180280370A1

公开(公告)日：2018-10-04

申请号：US15772302

申请日：2016-10-31

Applicant: Novartis AG

Inventor： Christian Schnell ,  Christine Fritsch ,  Emmanuelle di Tomaso ,  Cristian Massacesi ,  Lars Blumenstein

IPC: A61K31/4439 ,  A61K31/5377 ,  A61K31/553 ,  A61K31/519 ,  A61K31/506 ,  A61K9/00 ,  A61P35/00

Abstract: A method of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of a phosphatidylinositol 3-kinase inhibitor compound or a pharmaceutically acceptable salt thereof once-per-day either on a continuous daily schedule or an intermittent schedule at about zero to about three hours prior to sleep; a therapeutic regimen comprising administration of said compound or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

公开(公告)号：US20180325883A1

公开(公告)日：2018-11-15

申请号：US16033764

申请日：2018-07-12

Applicant: Novartis AG

Inventor： Saskia Maria Brachmann ,  Christine Fritsch ,  Sauveur-Michel Maira ,  Christian Schnell ,  Carlos Garcia-Echeverria

IPC: A61K31/4439 ,  A61K39/395 ,  C07K16/32 ,  A61K31/517 ,  A61K45/06 ,  A61K39/00

CPC classification number: A61K31/4439 ,  A61K31/517 ,  A61K39/3955 ,  A61K39/39558 ,  A61K45/06 ,  A61K2039/505 ,  A61K2300/00 ,  C07K16/32 ,  C07K2317/24

Abstract: The use of compounds of formula (I) in the treatment of Epidermal Growth Factor Receptor (EGFR) dependent diseases or diseases that have acquired resistance to agents that target EGFR family members, use of said compounds for the manufacture of pharmaceutical compositions for the treatment of said diseases, combinations of said compounds with EGFR modulators for said use, methods of treating said diseases with said compounds and pharmaceutical preparations for the treatment of said diseases comprising said compounds alone or in combination, especially with an EGFR modulator.

公开(公告)号：US20180085362A1

公开(公告)日：2018-03-29

申请号：US15715865

申请日：2017-09-26

Applicant: Novartis AG

Inventor： Christine Fritsch ,  Carlos Garcia-Echeverria ,  Xizhong Huang ,  Sauveur-Michel Maira

IPC: A61K31/4439 ,  A61K45/06 ,  A61K31/436

CPC classification number: A61K31/4439 ,  A61K31/427 ,  A61K31/436 ,  A61K31/439 ,  A61K31/506 ,  A61K45/06 ,  A61K2300/00

Abstract: The present invention relates to a pharmaceutical combination comprising a phosphatidylinositol-3-kinase (PI3K) inhibitor compound which is a 2-carboxamide cycloamino urea derivative or a pharmaceutically acceptable salt thereof and at least one mammalian target of rapamycin (mTOR) inhibitor or a pharmaceutically acceptable salt thereof; a pharmaceutical composition comprising such a combination; and the uses of such a combination in the treatment proliferative diseases, more specifically of mammalian target of rapamycin (mTOR) kinase dependent diseases.

公开(公告)号：US20140275089A1

公开(公告)日：2014-09-18

申请号：US14350577

申请日：2012-10-11

Applicant: NOVARTIS AG

Inventor： Xizhong Huang ,  Cornelia Quadt ,  Hui-Qin Wang ,  Christine Fritsch ,  Christian René Schnell

IPC: A61K31/5377 ,  A61K31/4439

CPC classification number: A61K31/5377 ,  A61K31/16 ,  A61K31/235 ,  A61K31/428 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/506 ,  A61K31/519 ,  A61K31/52 ,  A61K45/06 ,  A61K2300/00

Abstract: The present invention relates to a pharmaceutical combination comprising a 2-carboxamide cycloamino urea derivative compound of formula (I) and inhibitors of Heat Shock Protein 90, and the uses of such combinations in the treatment of proliferative diseases, more specifically PI3K dependent diseases, more specifically PI3K-alpha dependent diseases.

Abstract translation: 本发明涉及包含式（I）的2-甲酰胺环氨基脲衍生物化合物和热休克蛋白90抑制剂的药物组合，以及这些组合在治疗增殖性疾病中的用途，更具体地说是PI3K依赖性疾病 特别是PI3K-α依赖性疾病。

公开(公告)号：US20210196696A1

公开(公告)日：2021-07-01

申请号：US17105453

申请日：2020-11-25

Applicant: Novartis AG

Inventor： Emmanuelle di Tomaso ,  Christine Fritsch ,  Marie-Caroline Germa ,  Cristian Massacesi ,  Christian René Schnell ,  Ranjana Tavorath

IPC: A61K31/4439 ,  A61K9/00

Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

公开(公告)号：US20200069670A1

公开(公告)日：2020-03-05

申请号：US16556111

申请日：2019-08-29

Applicant: Novartis AG

Inventor： Emmanuelle di Tomaso ,  Marie-Caroline Germa ,  Cristian Massacesi ,  Christine Fritsch ,  Christian René Schnell ,  Ranjana Tavorath

IPC: A61K31/4439 ,  A61K9/00

Abstract: The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

公开(公告)号：US20150111927A1

公开(公告)日：2015-04-23

申请号：US14387653

申请日：2013-03-27

Applicant: NOVARTIS AG

Inventor： Pascal Furet ,  Christine Fritsch ,  Sauveur-Michel Maira

IPC: A61K31/4439 ,  C12Q1/68

CPC classification number: A61K31/4439 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156

Abstract: The present invention relates to selective cancer treatment regimes based on assaying for the presence or absence of a glutamine or a nucleic acid that encodes glutamine at position 859 of the catalytic p110α subunit of PI3K; methods for producing a transmittable form of information for predicting the responsiveness of patient to (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide), or a pharmaceutically acceptable salt thereof; and a kit thereof.

Abstract translation: 本发明涉及基于测定PI3K的催化性p110α亚基的位置859处谷氨酰胺或编码谷氨酰胺的核酸的存在或不存在的选择性癌症治疗方案; 用于产生用于预测患者对（S） - 吡咯烷-1,2-二羧酸2-酰胺1 - （{4-甲基-5- [2-（2,2,2-三氟乙基） 三氟-1,1-二甲基 - 乙基） - 吡啶-4-基] - 噻唑-2-基} - 酰胺）或其药学上可接受的盐; 及其套件。