AR110346A1 - Modulador del regulador de conductancia transmembrana de fibrosis quística, composiciones farmacéuticas, métodos de tratamiento y proceso para producir el modulador - Google Patents

Modulador del regulador de conductancia transmembrana de fibrosis quística, composiciones farmacéuticas, métodos de tratamiento y proceso para producir el modulador

Info

Publication number
AR110346A1
AR110346A1 ARP170103464A ARP170103464A AR110346A1 AR 110346 A1 AR110346 A1 AR 110346A1 AR P170103464 A ARP170103464 A AR P170103464A AR P170103464 A ARP170103464 A AR P170103464A AR 110346 A1 AR110346 A1 AR 110346A1
Authority
AR
Argentina
Prior art keywords
halogens
independently selected
alkyl groups
crystalline form
compound
Prior art date
Application number
ARP170103464A
Other languages
English (en)
Inventor
David A Siesel
Muna Shrestha
Yi Shi
Fabrice J D Pierre
Prasuna Paraselli
Mark T Miller
Jason Mcartney
Paul J Krenitsky
Haripada Khatuya
Ali Keshavarz-Shokri
Ping Kang
Pramod V Joshi
Robert M Hughes
Clara Kuang Hsia
- Hadida Ruah Sara S Ju
Anton Gulevich
Raymond S Gross
Peter D J Grootenhuis
Lori Ann Ferris
Thomas Cleveland
Jeremy J Clemens
Minson Baek
Paul T Angell
Corey Andersoy
Timothy Alcacio
Alexander R Abela
Jinglan Zhou
Timothy John Young
Goor Fredrick F Van
Johnny Uy
Andreas P Termin
Kathy Stavropoulos
Original Assignee
Vertex Pharma
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 Vertex Pharma filed Critical Vertex Pharma
Publication of AR110346A1 publication Critical patent/AR110346A1/es

Links

Classifications

    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • 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
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

También se describen composiciones farmacéuticas que los comprenden, su uso para el tratamiento de la fibrosis quística para confeccionarlos. Se describen además las formas en estado sólido del compuesto de fórmula (7) y sales y solvatos de este. Reivindicación 1: Un compuesto de fórmula (1), una sal farmacéuticamente aceptable de este o un derivado deuterado de cualquiera de los que anteceden, donde: uno de Y¹ e Y² es N el otro es CH; X se selecciona de grupos N(alquilo C₁₋₄), O y NH; R¹ es -(C(R²)₂)ₖ-O-(C(R²)₂)ₘR⁷; cada R² se selecciona independientemente de hidrógeno; halógenos; ciano; hidroxi; grupos alcoxi C₁₋₂; y grupos alquilo C₁₋₂ sustituidos opcionalmente con uno o más sustituyentes, donde cada uno se selecciona independientemente de halógenos, hidroxi y grupos cicloalquilo C₃₋₅ sustituidos opcionalmente con uno o más sustituyentes, donde cada uno se selecciona independientemente de grupos alquilo C₁₋₂, grupos alquilo C₁₋₂ halogenados y halógenos; cada R³ se selecciona independientemente de grupos alquilo C₁₋₄ sustituidos opcionalmente con uno o más grupos hidroxi, u opcionalmente, dos R³ germinales, junto con el átomo de carbono al cual se acoplan, forman un cicloalquilo C₃₋₄; cada R⁴ se selecciona independientemente de halógenos; R⁵ se selecciona de grupos alquilo C₁₋₄ e hidrógeno; cada R⁶ se selecciona independientemente de halógenos, ciano, hidroxi, hidroximetilo, grupos alcoxi C₁₋₂, grupos alquilo C₁₋₂ y grupos alquilo C₁₋₂ halogenados; R⁷ se selecciona de hidrógeno; halógenos; ciano; grupos alquilo C₁₋₂ sustituidos opcionalmente con uno o más sustituyentes, donde cada uno se selecciona independientemente de halógenos e hidroxi; y grupos cicloalquilo C₃₋₁₀ sustituidos opcionalmente con uno o más sustituyentes, donde cada uno se selecciona independientemente de grupos alquilo C₁₋₂, grupos alquilo C₁₋₂ halogenados y halógenos; k es 0 ó 1; r es 0 ó 1; m es 0, 1, 2 ó 3; p es 0, 1 ó 2; y q es 0, 1, 2, 3, 4, 5, 6, 7 u 8. Reivindicación 64: Un compuesto de fórmula (2) o una sal de este, o un derivado deuterado de cualquiera de los que anteceden, donde Xᵃ es F o Cl. Reivindicación 65: Un compuesto de fórmula (3) ó (4), o una sal de este, o un derivado deuterado de cualquiera de los que anteceden, donde, en cada una de dichas fórmulas: uno de Y¹ e Y² es independientemente N y el otro es independientemente CH; R¹ es -(C(R²)₂)ₖ-O-(C(R²)₂)ₘR⁷; cada R² se selecciona independientemente de hidrógeno; halógenos; ciano; hidroxi; grupos alcoxi C₁₋₂; y grupos alquilo C₁₋₂ sustituidos opcionalmente con uno o más sustituyentes, donde cada uno se selecciona independientemente de halógenos, hidroxi y grupos cicloalquilo C₃₋₅ sustituidos opcionalmente con uno o más sustituyentes, donde cada uno se selecciona independientemente de grupos alquilo C₁₋₂, grupos alquilo C₁₋₂ halogenados y halógenos; cada R⁴ se selecciona independientemente de halógenos; R⁷ se selecciona de hidrógeno, halógenos, ciano, grupos alquilo C₁₋₂ sustituidos opcionalmente con uno o más sustituyentes, donde cada uno se selecciona independientemente de halógenos e hidroxi, y grupos cicloalquilo C₃₋₁₀ sustituidos opcionalmente con uno o más sustituyentes, donde cada uno se selecciona independientemente de grupos alquilo C₁₋₂, grupos alquilo C₁₋₂ halogenados y halógenos; Rᵃ es alquilo C₁₋₄; Xᵃ es F o Cl; k es 0 ó 1; r es 0 ó 1; y m es 0, 1, 2 ó 3. Reivindicación 68: Un compuesto de fórmula (5) ó (6), o una sal de este, o un derivado deuterado de cualquiera de los que anteceden, donde Rᵃ es alquilo C₁₋₄; y cada Xᵃ es independientemente F o Cl. Reivindicación 72: Una Forma cristalina A del compuesto de fórmula (7). Reivindicación 74: La Forma cristalina A de acuerdo con la reivindicación 72, caracterizada por un difractograma en polvo de rayos X que posee una señal a al menos tres valores 2-q que se seleccionan de 6.6 ± 0.2, 7.6 ± 0.2, 9.6 ± 0.2, 12.4 ± 0.2, 13.1 ± 0.2, 15.2 ± 0.2, 16.4 ± 0.2, 18.2 ± 0.2 y 18.6 ± 0.2. Reivindicación 83: Una Forma cristalina M del compuesto de fórmula (7). Reivindicación 85: La Forma cristalina M de acuerdo con la reivindicación 83, caracterizada por un difractograma en polvo de rayos X que posee una señal a al menos tres valores 2-q que se seleccionan de 7.0 ± 0.2, 11.6 ± 0.2, 13.1 ± 0.2, 13.7 ± 0.2, 15.2 ± 0.2, 15.9 ± 0.2, 16.4 ± 0.2, 17.8 ± 0.2 y 19.3 ± 0.2. Reivindicación 90: Una Forma cristalina E del compuesto de fórmula (7). Reivindicación 92: La Forma cristalina E de acuerdo con la reivindicación 90, caracterizada por un difractograma en polvo de rayos X que posee una señal a al menos tres valores 2-q que se seleccionan de 7.0 ± 0.2, 11.2 ± 0.2, 12.8 ± 0.2, 13.2 ± 0.2, 14.1 ± 0.2, 15.1 ± 0.2, 16.1 ± 0.2, 17.8 ± 0.2 y 18.9 ± 0.2. Reivindicación 99: Una Forma cristalina X de una sal de potasio del compuesto de fórmula (7). Reivindicación 101: La Forma cristalina X de acuerdo con la reivindicación 99, caracterizada por un difractograma en polvo de rayos X que posee una señal a al menos tres valores 2-q que se seleccionan de 4.9 ± 0.2, 5.9 ± 0.2, 8.1 ± 0.2, 8.5 ± 0.2, 10.3 ± 0.2, 13.0 ± 0.2, 13.9 ± 0.2, 14.6 ± 0.2 y 17.0 ± 0.2. Reivindicación 106: Una Forma cristalina Y de una sal de sodio del compuesto de fórmula (7). Reivindicación 108: La Forma cristalina Y de acuerdo con la reivindicación 106, caracterizada por un difractograma en polvo de rayos X que posee una señal a al menos tres valores 2-q que se seleccionan de 3.5 ± 0.2, 7.0 ± 0.2, 11.7 ± 0.2, 12.8 ± 0.2, 13.2 ± 0.2, 14.2 ± 0.2, 15.4 ± 0.2, 16.6 ± 0.2 y 18.0 ± 0.2. Reivindicación 119: Una Forma cristalina P2 del compuesto de fórmula (7). Reivindicación 121: La Forma cristalina P2 de acuerdo con la reivindicación 119, caracterizada por un difractograma en polvo de rayos X que posee una señal a al menos tres valores 2-q que se seleccionan de 10.2 ± 0.2, 10.9 ± 0.2, 12.6 ± 0.2, 12.9 ± 0.2, 15.0 ± 0.2, 15.9 ± 0.2, 16.2 ± 0.2, 16.5 ± 0.2 y 17.6 ± 0.2.
ARP170103464A 2016-12-09 2017-12-12 Modulador del regulador de conductancia transmembrana de fibrosis quística, composiciones farmacéuticas, métodos de tratamiento y proceso para producir el modulador AR110346A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201662432537P 2016-12-09 2016-12-09

Publications (1)

Publication Number Publication Date
AR110346A1 true AR110346A1 (es) 2019-03-20

Family

ID=60953944

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP170103464A AR110346A1 (es) 2016-12-09 2017-12-12 Modulador del regulador de conductancia transmembrana de fibrosis quística, composiciones farmacéuticas, métodos de tratamiento y proceso para producir el modulador

Country Status (36)

Country Link
US (3) US10793547B2 (es)
EP (2) EP3551622B1 (es)
JP (3) JP6916285B2 (es)
KR (1) KR102269492B1 (es)
CN (2) CN110267948B (es)
AR (1) AR110346A1 (es)
AU (3) AU2017371200B2 (es)
BR (1) BR112019011626A2 (es)
CA (1) CA3046086A1 (es)
CL (1) CL2019001553A1 (es)
CO (1) CO2019007129A2 (es)
CY (1) CY1123736T1 (es)
DK (1) DK3551622T3 (es)
EA (2) EA202192783A1 (es)
EC (1) ECSP19048759A (es)
ES (1) ES2837431T3 (es)
GE (1) GEP20247634B (es)
HR (1) HRP20201946T1 (es)
HU (1) HUE052205T2 (es)
IL (3) IL294237A (es)
JO (1) JOP20190125B1 (es)
LT (1) LT3551622T (es)
MA (2) MA54847A (es)
MD (1) MD3551622T2 (es)
MX (2) MX2021013639A (es)
PE (2) PE20241131A1 (es)
PT (1) PT3551622T (es)
RS (1) RS61150B1 (es)
SA (1) SA519401947B1 (es)
SG (1) SG10201913606VA (es)
SI (1) SI3551622T1 (es)
TW (1) TWI774712B (es)
UA (1) UA128449C2 (es)
UY (2) UY37513A (es)
WO (1) WO2018107100A1 (es)
ZA (1) ZA201904062B (es)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG10201913603QA (en) 2014-10-06 2020-02-27 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
PL3436446T3 (pl) 2016-03-31 2023-09-11 Vertex Pharmaceuticals Incorporated Modulatory mukowiscydozowego przezbłonowego regulatora przewodnictwa
LT3519401T (lt) 2016-09-30 2021-11-25 Vertex Pharmaceuticals Incorporated Cistinės fibrozės transmembraninio laidumo reguliavimo moduliatorius, farmacinės kompozicijos, gydymo būdai ir moduliatoriaus gamybos būdas
US10793547B2 (en) 2016-12-09 2020-10-06 Vertex Pharmaceuticals Incorporated Modulator of the cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
AU2018279646B2 (en) 2017-06-08 2023-04-06 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
CA3069226A1 (en) * 2017-07-17 2019-01-24 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
CN111051280B (zh) * 2017-08-02 2023-12-22 弗特克斯药品有限公司 制备吡咯烷化合物的方法
CA3078893A1 (en) 2017-10-19 2019-04-25 Vertex Pharmaceuticals Incorporated Crystalline forms and compositions of cftr modulators
JP7245834B2 (ja) 2017-12-08 2023-03-24 バーテックス ファーマシューティカルズ インコーポレイテッド 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターを作成するためのプロセス
TWI810243B (zh) * 2018-02-05 2023-08-01 美商維泰克斯製藥公司 用於治療囊腫纖化症之醫藥組合物
PT3752510T (pt) * 2018-02-15 2023-03-15 Vertex Pharma Macrociclos como moduladores do regulador de condutância de transmembrana da fibrose cística, suas composições farmacêuticas, seu uso no tratamento da fibrose cística e processos para produzi-los
US11414439B2 (en) 2018-04-13 2022-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
AR118555A1 (es) * 2019-04-03 2021-10-20 Vertex Pharma Agentes moduladores del regulador de la conductancia transmembrana de la fibrosis quística
WO2020214921A1 (en) 2019-04-17 2020-10-22 Vertex Pharmaceuticals Incorporated Solid forms of modulators of cftr
WO2020242935A1 (en) * 2019-05-29 2020-12-03 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
TW202115092A (zh) 2019-08-14 2021-04-16 美商維泰克斯製藥公司 囊腫纖維化跨膜傳導調節蛋白之調節劑
TW202120517A (zh) 2019-08-14 2021-06-01 美商維泰克斯製藥公司 製備cftr調節劑之方法
BR112022002605A2 (pt) 2019-08-14 2022-05-03 Vertex Pharma Formas cristalinas de moduladores de cftr
CR20230120A (es) 2020-08-07 2023-09-01 Vertex Pharma Moduladores del regulador de la conductancia transmembrana de la fibrosis quística
AU2023215372A1 (en) 2022-02-03 2024-08-22 Vertex Pharmaceuticals Incorporated Methods of preparing and crystalline forms of (6a,12a)-17-amino-12-methyl-6,15-bis(trifluoromethyl)-13,19-dioxa-3,4,18-triazatricyclo[ 12.3.1.12,5]nonadeca-1(18),2,4,14,16-pentaen-6-ol
WO2023150237A1 (en) 2022-02-03 2023-08-10 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
WO2023154291A1 (en) 2022-02-08 2023-08-17 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
WO2023224924A1 (en) 2022-05-16 2023-11-23 Vertex Pharmaceuticals Incorporated Solid forms of a macrocyclic compounds as cftr modulators and their preparation
WO2023224931A1 (en) 2022-05-16 2023-11-23 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
WO2023240267A2 (en) * 2022-06-10 2023-12-14 Sionna Therapeutics Compounds, compositions, and methods of using thereof
WO2024031081A1 (en) 2022-08-04 2024-02-08 Vertex Pharmaceuticals Incorporated Compositions for the treatment of cftr-mediated diseases
WO2024056791A1 (en) 2022-09-15 2024-03-21 Idorsia Pharmaceuticals Ltd Combination of macrocyclic cftr modulators with cftr correctors and / or cftr potentiators
WO2024056798A1 (en) 2022-09-15 2024-03-21 Idorsia Pharmaceuticals Ltd Macrocyclic cftr modulators

Family Cites Families (226)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1117936A (en) * 1914-03-04 1914-11-17 Harry H West Circular-knitting machine.
EP0194599A3 (en) 1985-03-14 1988-01-20 Nissan Chemical Industries Ltd. Benzamide derivatives, process for producing the same, and soil fungicides containing the same
GB9122590D0 (en) 1991-10-24 1991-12-04 Lilly Industries Ltd Pharmaceutical compounds
DE4410453A1 (de) 1994-03-25 1995-09-28 Hoechst Ag Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel
GB9514160D0 (en) 1994-07-25 1995-09-13 Zeneca Ltd Aromatic compounds
PL321244A1 (en) 1995-01-19 1997-11-24 Ciba Geigy Ag Insecticide composition
WO1997018712A1 (en) 1995-11-23 1997-05-29 Novartis Ag Herbicidal composition
CA2238875C (en) 1995-12-15 2003-09-16 Merck Frosst Canada Inc. Tri-aryl ethane derivatives as pde iv inhibitors
CA2264020A1 (en) 1996-08-26 1998-03-05 Jean Bemis Inhibitors of phospholipase enzymes
JPH10114654A (ja) 1996-10-09 1998-05-06 Fujisawa Pharmaceut Co Ltd 新規用途
AU6209098A (en) 1997-01-15 1998-08-07 Novartis Ag Herbicidal agent
GB9716657D0 (en) 1997-08-07 1997-10-15 Zeneca Ltd Chemical compounds
DE19742951A1 (de) 1997-09-29 1999-04-15 Hoechst Schering Agrevo Gmbh Acylsulfamoylbenzoesäureamide, diese enthaltende nutzpflanzenschützende Mittel und Verfahren zu ihrer Herstellung
DE19802697A1 (de) 1998-01-24 1999-07-29 Bayer Ag Selektive Herbizide auf Basis von N-Aryl-triazolin(thi)onen und N-Arylsulfonylamino(thio)carbonyltriazolin(thi)onen
EP1069112A4 (en) 1998-02-13 2001-04-18 Kureha Chemical Ind Co Ltd N- (PHENYLSULFONYL) PICOLINAMIDE DERIVATIVES, METHOD FOR THEIR PREPARATION AND HERBICIDES
EP1070705A4 (en) 1998-04-06 2002-04-17 Fujisawa Pharmaceutical Co INDOLE DERIVATIVES
SK17622001A3 (sk) 1999-06-10 2003-06-03 Warner-Lambert Company Izoindolínové deriváty, ich použitie a farmaceutické kompozície na ich báze
DE19936438A1 (de) 1999-08-03 2001-02-08 Aventis Cropscience Gmbh Kombinationen von Herbiziden und Safenern
DE19940860A1 (de) 1999-08-27 2001-03-01 Bayer Ag Selektive Herbizide auf Basis eines substituierten Phenylsulfonyl aminocarbonyltriazolinons und Safenern II
DE19958381A1 (de) 1999-12-03 2001-06-07 Bayer Ag Herbizide auf Basis von N-Aryl-uracilen
AU2001286557A1 (en) 2000-08-23 2002-03-04 Merck Frosst Canada And Co. Method of treating or preventing urinary incontinence using prostanoid ep1 receptor antagonists
AR031130A1 (es) 2000-09-20 2003-09-10 Abbott Lab N-acilsulfonamidas promotoras de la apoptosis
US20020055631A1 (en) 2000-09-20 2002-05-09 Augeri David J. N-acylsulfonamide apoptosis promoters
US6720338B2 (en) 2000-09-20 2004-04-13 Abbott Laboratories N-acylsulfonamide apoptosis promoters
EP1341761A1 (en) 2000-10-10 2003-09-10 Smithkline Beecham Corporation SUBSTITUTED INDOLES, PHARMACEUTICAL COMPOSITIONS CONTAINING SUCH INDOLES AND THEIR USE AS PPAR-$g(g) BINDING AGENTS
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
DE10119721A1 (de) 2001-04-21 2002-10-31 Bayer Cropscience Gmbh Herbizide Mittel enthaltend Benzoylcyclohexandione und Safener
CA2449150C (en) 2001-05-31 2011-07-12 Vicore Pharma Ab Tricyclic compounds useful as angiotensin ii agonists
CN1522246B (zh) 2001-06-28 2010-04-21 辉瑞产品公司 三酰胺取代的吲哚、苯并呋喃及苯并噻吩
DE10145019A1 (de) 2001-09-13 2003-04-03 Bayer Cropscience Gmbh Kombinationen aus Herbiziden und Safenern
DE10146873A1 (de) 2001-09-24 2003-04-17 Bayer Cropscience Gmbh Heterocyclische Amide und -Iminderivate, Verfahren zu ihrer Herstellung, sie enthaltende Mittel und ihre Verwendung als Schädlingsbekämpfungsmittel
WO2003048135A1 (en) 2001-11-14 2003-06-12 Teva Pharmaceutical Industries Ltd. Amorphous and crystalline forms of losartan potassium and process for their preparation
WO2003043655A1 (fr) 2001-11-19 2003-05-30 Ono Pharmaceutical Co., Ltd. Remedes pour la frequence urinaire
DE10157545A1 (de) 2001-11-23 2003-06-12 Bayer Cropscience Gmbh Herbizide Mittel enthaltend Benzoylpyrazole und Safener
US7247748B2 (en) 2002-03-27 2007-07-24 Smithkline Corporation Amide compounds and methods of using the same
GB0212785D0 (en) 2002-05-31 2002-07-10 Glaxo Group Ltd Compounds
RS51816B (en) 2002-06-08 2011-12-31 Bayer Cropscience Ag. COMBINATION OF HERBICIDIC AROMATIC CARBONIC ACIDS AND PROTECTANTS
DE10237461A1 (de) 2002-08-16 2004-02-26 Bayer Cropscience Gmbh Herbizide Mittel enthaltend Benzoylpyrazole und Safener
US20060019932A1 (en) 2002-09-06 2006-01-26 Mancini Joseph A Treatment of rheumatoid arthritis by inhibition of pde4
CA2503063A1 (en) 2002-10-22 2004-05-06 Merck Frosst Canada & Co./Merck Frosst Canada & Cie Nitric oxide releasing selective cyclooxygenase-2 inhibitors
GB0225548D0 (en) 2002-11-01 2002-12-11 Glaxo Group Ltd Compounds
AU2003302106A1 (en) 2002-11-21 2004-06-15 Vicore Pharma Ab New tricyclic angiotensin ii agonists
MXPA05006744A (es) 2002-12-20 2005-09-08 Pfizer Prod Inc Inhibidores de la proteina microsomal de transferencia de trigliceridos.
CA2510815A1 (en) 2002-12-20 2004-07-08 Pfizer Products Inc. Microsomal triglyceride transfer protein inhibitors
WO2004078114A2 (en) 2003-02-28 2004-09-16 Encysive Pharmaceuticals Inc. Pyridine, pyrimidine, quinoline, quinazoline, and naphthalene urotensin-ii receptor antagonists.
AU2003219291A1 (en) 2003-03-24 2004-10-18 Vicore Pharma Ab Bicyclic compounds useful as angiotensin ii agonists
DE602004022819D1 (de) 2003-06-06 2009-10-08 Vertex Pharma Von atp-bindende kassette transportern
NZ547220A (en) 2003-11-14 2009-12-24 Vertex Pharma Thiazoles and oxazoles useful as modulators of ATP-binding cassette transporters
GB0328024D0 (en) 2003-12-03 2004-01-07 Glaxo Group Ltd Compounds
US20090131342A1 (en) 2004-01-22 2009-05-21 Nitromed, Inc. Nitrosated and/or nitrosylated compounds, compositions and methods of use
US7977322B2 (en) 2004-08-20 2011-07-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
BRPI0507278A (pt) 2004-01-30 2007-06-26 Vertex Pharma moduladores dos transportadores do cassete de ligação ao atp
EP1716137A1 (en) 2004-02-04 2006-11-02 Pfizer Products Incorporated Substituted quinoline compounds
TW200533336A (en) 2004-03-02 2005-10-16 Fujisawa Pharmaceutical Co Concomitant drugs
DK1731512T3 (en) 2004-03-05 2015-01-05 Nissan Chemical Ind Ltd Isoxazoline-substituted benzamide AND INSTRUMENTS FOR COMBATING HARMFUL ORGANISMS
WO2005099705A2 (en) 2004-03-24 2005-10-27 Bayer Pharmaceuticals Corporation Preparation of imidazole derivatives and methods of use
US7414037B2 (en) 2004-03-30 2008-08-19 The Regents Of The University Of California Hydrazide-containing CFTR inhibitor compounds and uses thereof
GB0410121D0 (en) 2004-05-06 2004-06-09 Glaxo Group Ltd Compounds
BR122018075478B8 (pt) 2004-06-24 2023-10-31 Vertex Pharma moduladores de transportadores de cassete de ligação de atp
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
EP1790638B1 (en) 2004-09-15 2013-04-03 Shionogi Co., Ltd. Carbamoylpyridone derivative having hiv integrase inhibitory activity
US7205296B2 (en) 2004-09-29 2007-04-17 Portola Pharmaceuticals, Inc. Substituted 2H-1,3-benzoxazin-4(3H)-ones
WO2006065204A1 (en) 2004-12-14 2006-06-22 Astrazeneca Ab Substituted aminopyridines and uses thereof
GB0428173D0 (en) 2004-12-23 2005-01-26 Astrazeneca Ab Compounds
ES2321535T3 (es) 2004-12-23 2009-06-08 Glaxo Group Limited Compuestos de piridina para el tratamiento de enfermedades mediadas por prostaglandinas.
US20070032488A1 (en) 2005-08-05 2007-02-08 Genelabs Technologies, Inc. 6-Membered aryl and heteroaryl derivatives for treating viruses
JP5143738B2 (ja) 2005-08-11 2013-02-13 バーテックス ファーマシューティカルズ インコーポレイテッド 嚢胞性線維症膜コンダクタンス制御因子の調節物質
WO2007053641A2 (en) 2005-11-01 2007-05-10 Mars, Incorporated A-type procyanidins and inflammation
ES2439736T3 (es) * 2005-11-08 2014-01-24 Vertex Pharmaceuticals Incorporated Moduladores heterocíclicos de transportadores de casete de unión a ATP
CA2635214A1 (en) 2005-12-27 2007-07-05 Vertex Pharmaceuticals Incorporated Compounds useful in cftr assays and methods therewith
CA2856037C (en) 2005-12-28 2017-03-07 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US7671221B2 (en) 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
HUE049976T2 (hu) 2005-12-28 2020-11-30 Vertex Pharma N-[2,4-bisz(1,1-dimetil-etil)-5-hidroxi-fenil]-1,4-dihidro-4-oxo-kinolin-3-karboxamid amorf alakjának gyógyászati kompozíciói
EP2007745A2 (en) 2006-04-05 2008-12-31 Bayer CropScience S.A. Fungicide n-cyclopropyl-sulfonylamide derivatives
RU2451018C2 (ru) 2006-04-07 2012-05-20 Вертекс Фармасьютикалз Инкорпорейтед Модуляторы атф-связывающих кассетных транспортеров
AU2007249269A1 (en) 2006-05-12 2007-11-22 Vertex Pharmaceuticals Incorporated Compositions of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide
US8778977B2 (en) 2006-06-30 2014-07-15 Sunesis Pharmaceuticals, Inc. Pyridinonyl PDK1 inhibitors
EP2118103B1 (en) 2006-11-03 2014-04-23 Vertex Pharmaceuticals Inc. Azaindole derivatives as cftr modulators
US7754739B2 (en) 2007-05-09 2010-07-13 Vertex Pharmaceuticals Incorporated Modulators of CFTR
CN101687789A (zh) 2007-02-12 2010-03-31 因特蒙公司 C型肝炎病毒复制的新颖抑制剂
WO2008141385A1 (en) 2007-05-21 2008-11-27 Biota Scientific Management Pty Ltd Viral polymerase inhibitors
US8058299B2 (en) 2007-05-22 2011-11-15 Via Pharmaceuticals, Inc. Diacylglycerol acyltransferase inhibitors
WO2008147544A1 (en) 2007-05-25 2008-12-04 Amgen Inc. Substituted hydroxyethyl amine compounds as beta-secretase modulators and methods of use
GB0716532D0 (en) 2007-08-24 2007-10-03 Angeletti P Ist Richerche Bio Therapeutic compounds
AU2008295476B2 (en) 2007-08-29 2013-08-01 Merck Sharp & Dohme Corp. 2, 3-Substituted Indole Derivatives for treating viral infections
NZ600865A (en) 2007-09-14 2014-01-31 Vertex Pharma Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
JP5249344B2 (ja) 2007-11-16 2013-07-31 メルク・シャープ・アンド・ドーム・コーポレーション ヘテロ環の３位が置換されたインドール誘導体およびその使用
AU2013231151B2 (en) 2007-11-16 2015-06-25 Vertex Pharmaceuticals Incorporated Isoquinoline modulators of ATP-Binding Cassette transporters
GB0723794D0 (en) 2007-12-05 2008-01-16 Lectus Therapeutics Ltd Potassium ion channel modulators and uses thereof
CN101910156B (zh) 2007-12-07 2013-12-04 沃泰克斯药物股份有限公司 3-(6-(1-(2,2-二氟苯并[d][1,3]间二氧杂环戊烯-5-基)环丙烷甲酰氨基)-3-甲基吡啶-2-基)苯甲酸的固体形式
CA2989620C (en) 2007-12-07 2022-05-03 Vertex Pharmaceuticals Incorporated Processes for producing cycloalkylcarboxamido-pyridine benzoic acids
AU2013270464B2 (en) 2008-03-31 2016-05-26 Vertex Pharmaceuticals Incorporated Pyridyl derivatives as CFTR modulators
US20110071197A1 (en) 2008-04-16 2011-03-24 Peter Nilsson Bis-aryl compounds for use as medicaments
US20110112193A1 (en) 2008-05-14 2011-05-12 Peter Nilsson Bis-aryl compounds for use as medicaments
EP2145537A1 (en) 2008-07-09 2010-01-20 Bayer CropScience AG Plant growth regulator
UY31982A (es) 2008-07-16 2010-02-26 Boehringer Ingelheim Int Derivados de 1,2-dihidropiridin-3-carboxamidas n-sustituidas
JP5575768B2 (ja) 2008-08-13 2014-08-20 バーテックス ファーマシューティカルズ インコーポレイテッド 薬学的組成物およびその投与
EP2326178A4 (en) 2008-08-21 2012-10-24 Glaxosmithkline Llc INHIBITORS OF PROLYL-HYDROXYLASE
CN102256969A (zh) 2008-08-27 2011-11-23 钙医学公司 调节胞内钙的化合物
CN102164587A (zh) 2008-09-29 2011-08-24 沃泰克斯药物股份有限公司 3-(6-(1-(2,2-二氟苯并[d][1,3]间二氧杂环戊烯-5-基)环丙烷甲酰氨基)-3-甲基吡啶-2-基)苯甲酸的剂量单元
EA018891B1 (ru) 2008-10-23 2013-11-29 Вертекс Фармасьютикалз, Инкорпорейтед Модуляторы регулятора трансмембранной проводимости при муковисцидозе
UA121188C2 (uk) 2008-11-06 2020-04-27 Вертекс Фармасьютікалз Інкорпорейтед Модулятори атф-зв'язувальних касетних транспортерів
UA104876C2 (uk) 2008-11-06 2014-03-25 Вертекс Фармасьютікалз Інкорпорейтед Модулятори atф-зв'язувальних касетних транспортерів
US20100160322A1 (en) 2008-12-04 2010-06-24 Abbott Laboratories Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
UA108193C2 (uk) 2008-12-04 2015-04-10 Апоптозіндукуючий засіб для лікування раку і імунних і аутоімунних захворювань
EP2382197B1 (en) 2008-12-30 2016-10-05 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
NZ593593A (en) 2009-01-19 2013-11-29 Abbvie Inc Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
WO2010102758A2 (de) 2009-03-11 2010-09-16 Bayer Cropscience Ag Halogenalkylmethylenoxy-phenyl-substituierte ketoenole
SG10201504084QA (en) 2009-03-20 2015-06-29 Vertex Pharma Process for making modulators of cystic fibrosis transmembrane conductance regulator
CA2755969C (en) 2009-03-20 2018-05-08 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
JP5697163B2 (ja) 2009-03-26 2015-04-08 塩野義製薬株式会社 置換された３−ヒドロキシ−４−ピリドン誘導体
CN102458122A (zh) 2009-04-20 2012-05-16 人类健康研究所 含有哒嗪磺胺衍生物的化合物、组合物和方法
HUE027698T2 (en) 2009-05-26 2016-10-28 Abbvie Bahamas Ltd Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases
WO2011102514A1 (ja) 2010-02-22 2011-08-25 武田薬品工業株式会社 芳香環化合物
CN103180298A (zh) 2010-03-19 2013-06-26 沃泰克斯药物股份有限公司 N-[2,4-双(1,1-二甲基乙基)-5-羟基苯基]-1,4-二氢-4-氧代喹啉-3-甲酰胺的固体形式
PT2826776T (pt) 2010-03-25 2021-02-01 Vertex Pharma Forma amorfa sólida de (r)-1(2,2-difluorobenzo(d)(1,3)dioxol-5-ilo)-n-(1-(2,3-dihidroxipropilo)-6-fluoro-2-(1-hidroxi-2-metilpropan-2-ilo)-1h-indol-5-ilo)-ciclopropanocarboxamida
BR112012026257A2 (pt) 2010-04-07 2017-03-14 Vertex Pharma formas sólidas de ácido 3-(6-(1-(2-,2-difluorbenzo[d][1,3]dioxol-5-il)ciclopropanocarboxamido)-3-metilpiridin-2-il)benzóico
DK3150198T3 (da) 2010-04-07 2021-11-01 Vertex Pharma Farmaceutiske sammensætninger af 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioxol-5-yl)-cyclopropancarboxamido)-3-methylpyriodin-2-yl)benzoesyre og indgivelse deraf
US8344137B2 (en) 2010-04-14 2013-01-01 Hoffman-La Roche Inc. 3,3-dimethyl tetrahydroquinoline derivatives
EP2560649A1 (en) 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
MX2012012204A (es) 2010-04-22 2012-12-05 Vertex Pharma Proceso para producir compuestos de cicloalquilcarboxamido-indol.
TWI520960B (zh) 2010-05-26 2016-02-11 艾伯維有限公司 用於治療癌症及免疫及自體免疫疾病之細胞凋亡誘導劑
US8563593B2 (en) 2010-06-08 2013-10-22 Vertex Pharmaceuticals Incorporated Formulations of (R)-1-(2,2-difluorobenzo[D] [1,3] dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide
MX2013002035A (es) 2010-08-23 2013-03-25 Vertex Pharma Composiciones farmaceuticas de (r)-1-(2, 2-difluorobenzo[d] [1, 3]dioxol-5-il)-n-(1-(2, 3-dihidroxipropil)-6-fluoro-2-(1-hidroxi-2 -metilpropano-2-il)-1h-indol-5-il) ciclopropanocarboxamida y administracion de las mismas.
RU2013113627A (ru) 2010-08-27 2014-10-10 Вертекс Фармасьютикалз Инкорпорейтед Фармацевтическая композиция и ее введения
US9394290B2 (en) 2010-10-21 2016-07-19 Universitaet Des Saarlandes Campus Saarbruecken Selective CYP11B1 inhibitors for the treatment of cortisol dependent diseases
WO2012087938A1 (en) 2010-12-20 2012-06-28 Glaxosmithkline Llc Quinazolinone derivatives as antiviral agents
EP2471363A1 (de) 2010-12-30 2012-07-04 Bayer CropScience AG Verwendung von Aryl-, Heteroaryl- und Benzylsulfonamidocarbonsäuren, -carbonsäureestern, -carbonsäureamiden und -carbonitrilen oder deren Salze zur Steigerung der Stresstoleranz in Pflanzen
CA2825746A1 (en) 2011-01-26 2012-08-02 Kyorin Pharmaceutical Co. Ltd. Pyrazolopyridine derivative or pharmacologically acceptable salt thereof
JP2014508752A (ja) 2011-02-17 2014-04-10 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 治療用の置換３−（ビフェニル−３−イル）−８，８−ジフルオロ−４−ヒドロキシ−１−アザスピロ［４．５］デカ−３−エン−２−オン
EP2681191B1 (de) 2011-03-01 2015-09-02 Bayer Intellectual Property GmbH 2-acyloxy-pyrrolin-4-one
AR085585A1 (es) 2011-04-15 2013-10-09 Bayer Cropscience Ag Vinil- y alquinilciclohexanoles sustituidos como principios activos contra estres abiotico de plantas
HUE047354T2 (hu) 2011-05-18 2020-04-28 Vertex Pharmaceuticals Europe Ltd Ivacaftor deuterizált származékai
US9260416B2 (en) 2011-05-27 2016-02-16 Amira Pharmaceuticals, Inc. Heterocyclic autotaxin inhibitors and uses thereof
AU2012300246A1 (en) 2011-08-30 2014-03-06 Chdi Foundation, Inc. Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof
JP6138797B2 (ja) 2011-09-16 2017-05-31 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ 植物収量を向上させるためのアシルスルホンアミド類の使用
WO2013038373A1 (en) 2011-09-16 2013-03-21 Novartis Ag Pyridine amide derivatives
US9226505B2 (en) 2011-09-23 2016-01-05 Bayer Intellectual Property Gmbh 4-substituted 1-phenylpyrazole-3-carboxylic acid derivatives as agents against abiotic plant stress
ME02650B (me) 2011-11-08 2017-06-20 Vertex Pharma Modulatori atp- vezujućih kasetnih transportera
US8426450B1 (en) 2011-11-29 2013-04-23 Helsinn Healthcare Sa Substituted 4-phenyl pyridines having anti-emetic effect
CA2862859C (en) 2012-01-25 2022-08-02 Vertex Pharmaceuticals Incorporated Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
JP2015083542A (ja) 2012-02-08 2015-04-30 大日本住友製薬株式会社 ３位置換プロリン誘導体
CN109966264A (zh) 2012-02-27 2019-07-05 沃泰克斯药物股份有限公司 药物组合物及其施用
US8889730B2 (en) 2012-04-10 2014-11-18 Pfizer Inc. Indole and indazole compounds that activate AMPK
AU2012377446A1 (en) 2012-04-20 2014-10-23 Vertex Pharmaceuticals Incorporated Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
SG11201408284VA (en) 2012-05-22 2015-02-27 Xenon Pharmaceuticals Inc N-substituted benzamides and their use in the treatment of pain
AU2013270681A1 (en) 2012-06-08 2014-12-18 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for the treatment of CFTR -mediated disorders
WO2013185202A1 (en) 2012-06-14 2013-12-19 Beta Pharma Canada Inc Apoptosis inducers
WO2014008458A2 (en) 2012-07-06 2014-01-09 Genentech, Inc. N-substituted benzamides and methods of use thereof
AR092857A1 (es) 2012-07-16 2015-05-06 Vertex Pharma Composiciones farmaceuticas de (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-il)-n-(1-(2,3-dihidroxipropil)-6-fluoro-2-(1-hidroxi-2-metilpropan-2-il)-1h-indol-5-il)ciclopropancarboxamida y administracion de las mismas
JP2015178458A (ja) 2012-07-25 2015-10-08 杏林製薬株式会社 ベンゼン環縮合含窒素５員複素環式化合物、またはその薬理学的に許容される塩
CN103571906B (zh) 2012-07-27 2018-12-11 上海泽元海洋生物技术有限公司 一种利用微藻高效生产虾青素的新方法
CN104736153B (zh) 2012-08-13 2018-06-29 艾伯维公司 细胞凋亡诱导剂
DK2888251T3 (da) 2012-08-21 2019-07-29 Peter Maccallum Cancer Inst Perforinhæmmende benzensulfonamidforbindelser, fremstilling og anvendelser deraf
WO2014039714A2 (en) 2012-09-06 2014-03-13 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US10093640B2 (en) 2012-09-21 2018-10-09 Vanderbilt University Substituted benzofuran, benzothiophene and indole MCL-1 inhibitors
EP2917203B1 (en) 2012-11-02 2019-04-03 Dana-Farber Cancer Institute, Inc. Method for identifying myc inhibitors
IL283276B2 (en) 2012-11-02 2024-05-01 Vertex Pharma Preparations containing 3-(6-(1-(2,2-difluorobenzo[1,3][D]dioxol-5-yl)cycloproponecarboxamide)-3-methylpyridin-2-yl)benzoic acid and N-(5-hydroxy- 2,4-di-tert-butyl-phenyl)-4-oxo-H1-quinoline-3-carboxamide and their uses
CN104955459B (zh) 2012-11-05 2019-02-01 南特知识产权控股有限责任公司 取代的吲哚-5-酚衍生物及其治疗应用
WO2014086723A1 (de) 2012-12-05 2014-06-12 Bayer Cropscience Ag Verwendung substituierter 1-(arylethinyl)-, 1-(heteroarylethinyl)-, 1-(heterocyclylethinyl)- und 1-(cyloalkenylethinyl)-bicycloalkanole als wirkstoffe gegen abiotischen pflanzenstress
BR112015012926A2 (pt) 2012-12-05 2017-07-11 Bayer Cropscience Ag uso de 1-(aril etinil)-, 1-(heteroaril etinil)-, 1-(heterociclil etinil)- substituído e 1-(cicloalquenil etinil)-ciclohexanóis como agentes ativos contra o estresse abiótico da planta
UA115576C2 (uk) 2012-12-06 2017-11-27 Байєр Фарма Акцієнгезелльшафт Похідні бензимідазолу як антагоністи ер4
GB201223265D0 (en) 2012-12-21 2013-02-06 Selvita Sa Novel benzimidazole derivatives as kinase inhibitors
US20150353542A1 (en) 2013-01-14 2015-12-10 Amgen Inc. Methods of using cell-cycle inhibitors to modulate one or more properties of a cell culture
DK2968304T3 (en) 2013-03-14 2019-01-28 Univ Columbia 4-PHENYLPIPERIDINES, THEIR PREPARATION AND USE.
US9637450B2 (en) 2013-03-14 2017-05-02 The Trustees Of Columbia University In The City Of New York Octahydrocyclopentapyrroles, their preparation and use
KR102362835B1 (ko) 2013-03-15 2022-02-14 사이클리온 테라퓨틱스, 인크. ｓＧＣ 자극인자
PT2978752T (pt) 2013-03-29 2018-03-09 Takeda Pharmaceuticals Co Derivados de 6-(5-hidroxi-1h-pirazol-1-il)nicotinamida e o seu uso como inibidores de phd
AU2014264936B2 (en) 2013-05-07 2018-09-27 Galapagos Nv Novel compounds and pharmaceutical compositions thereof for the treatment of cystic fibrosis
WO2014181287A1 (en) 2013-05-09 2014-11-13 Piramal Enterprises Limited Heterocyclyl compounds and uses thereof
AU2014268477A1 (en) 2013-05-24 2015-11-12 The California Institute For Biomedical Research Compounds for treatment of drug resistant and persistent tuberculosis
WO2015010832A1 (en) 2013-07-22 2015-01-29 Syngenta Participations Ag Microbiocidal heterocyclic derivatives
WO2015031608A1 (en) 2013-08-28 2015-03-05 Vanderbilt University Substituted indole mcl-1 inhibitors
US9663508B2 (en) 2013-10-01 2017-05-30 Amgen Inc. Biaryl acyl-sulfonamide compounds as sodium channel inhibitors
WO2015069287A1 (en) 2013-11-08 2015-05-14 Allergan, Inc. Compounds as tyrosine kinase modulators
US10231932B2 (en) 2013-11-12 2019-03-19 Vertex Pharmaceuticals Incorporated Process of preparing pharmaceutical compositions for the treatment of CFTR mediated diseases
ES2957761T3 (es) * 2014-04-15 2024-01-25 Vertex Pharma Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
SG10201913603QA (en) 2014-10-06 2020-02-27 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
CN107250113B (zh) 2014-10-07 2019-03-29 弗特克斯药品有限公司 囊性纤维化跨膜传导调节蛋白的调节剂的共晶
JP6494757B2 (ja) 2014-11-18 2019-04-03 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ ハイスループット試験高速液体クロマトグラフィーを行うプロセス
CA2971855A1 (en) 2014-12-23 2016-06-30 Proteostasis Therapeutics, Inc. Derivatives of 5-(hetero)arylpyrazol-3-carboxylic amide or 1-(hetero)aryltriazol-4-carboxylic amide useful for the treatment of inter alia cystic fibrosis
MA41253A (fr) 2014-12-23 2017-10-31 Proteostasis Therapeutics Inc Composés, compositions et procédés pour augmenter l'activité du cftr
JP6700291B2 (ja) 2015-02-15 2020-05-27 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ １−（ｈｅｔ）アリールスルホニル−（ピロリジン又はピペリジン）−２−カルボキサミド誘導体、及びｔｒｐａ１拮抗薬としてのそれらの使用
CA2981495C (en) 2015-03-31 2023-09-26 Vertex Pharmaceuticals (Europe) Limited Deuterated vx-661
MX2018003331A (es) 2015-09-21 2018-08-16 Vertex Pharmaceuticals Europe Ltd Administracion de potenciadores de regulador de la conductancia transmembrana de fibrosis quistica (cftr) deuterados.
JP2019513714A (ja) 2016-03-30 2019-05-30 ジェネンテック， インコーポレイテッド 置換ベンズアミド及びその使用方法
PL3436446T3 (pl) 2016-03-31 2023-09-11 Vertex Pharmaceuticals Incorporated Modulatory mukowiscydozowego przezbłonowego regulatora przewodnictwa
NZ746793A (en) 2016-04-07 2022-10-28 Proteostasis Therapeutics Inc Silicone atoms containing ivacaftor analogues
BR112018072047A2 (pt) 2016-04-26 2019-02-12 AbbVie S.à.r.l. moduladores da proteína reguladora de condutância transmembranar de fibrose cística
US10138227B2 (en) 2016-06-03 2018-11-27 Abbvie S.Á.R.L. Heteroaryl substituted pyridines and methods of use
US10899751B2 (en) 2016-06-21 2021-01-26 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
LT3519401T (lt) 2016-09-30 2021-11-25 Vertex Pharmaceuticals Incorporated Cistinės fibrozės transmembraninio laidumo reguliavimo moduliatorius, farmacinės kompozicijos, gydymo būdai ir moduliatoriaus gamybos būdas
US10399940B2 (en) 2016-10-07 2019-09-03 Abbvie S.Á.R.L. Substituted pyrrolidines and methods of use
US9981910B2 (en) 2016-10-07 2018-05-29 Abbvie S.Á.R.L. Substituted pyrrolidines and methods of use
EP3532461A1 (en) 2016-10-26 2019-09-04 Proteostasis Therapeutics, Inc. N-phenyl-2-(3-phenyl-6-oxo-1,6-dihydropyridazin-1-yl)acetamide derivatives for treating cystic fibrosis
EP3532469A1 (en) 2016-10-26 2019-09-04 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for modulating cftr
WO2018081381A1 (en) 2016-10-26 2018-05-03 Proteostasis Therapeutics, Inc Pyridazine derivatives, compositions and methods for modulating cftr
KR20230146104A (ko) 2016-11-18 2023-10-18 시스틱 파이브로시스 파운데이션 Cftr 강화제로서의 피롤로피리미딘
US10793547B2 (en) 2016-12-09 2020-10-06 Vertex Pharmaceuticals Incorporated Modulator of the cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
US10131670B2 (en) 2016-12-16 2018-11-20 Cystic Fibrosis Foundation Therapeutics, Inc. Bicyclic heteroaryl derivatives as CFTR potentiators
EP3558982A1 (en) 2016-12-20 2019-10-30 AbbVie S.À.R.L. Deuterated cftr modulators and methods of use
US11053239B2 (en) 2017-01-07 2021-07-06 Fochon Pharmaceuticals, Ltd. Compounds as BLC-2-selective apoptosis-inducing agents
TW201831471A (zh) 2017-02-24 2018-09-01 盧森堡商艾伯維公司 囊腫纖化症跨膜傳導調節蛋白的調節劑及其使用方法
WO2018183367A1 (en) 2017-03-28 2018-10-04 Van Goor Fredrick F Methods of treating cystic fibrosis in patients with residual function mutations
MA49061A (fr) 2017-04-28 2021-04-21 Proteostasis Therapeutics Inc Dérivés 4-sulfonylaminocarbonylquinoline pour augmenter l'activité cftr
AU2018279646B2 (en) 2017-06-08 2023-04-06 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
CA3068609A1 (en) 2017-07-01 2019-01-10 Vertex Pharmaceuticals Incorporated Compositions and methods for treatment of cystic fibrosis
WO2019018353A1 (en) 2017-07-17 2019-01-24 Vertex Pharmaceuticals Incorporated METHODS OF TREATING CYSTIC FIBROSIS
CA3069226A1 (en) 2017-07-17 2019-01-24 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
US11427858B2 (en) 2017-07-31 2022-08-30 Technion Research & Development Foundation Limited Methods of detecting modified and unmodified DNA
CN111051280B (zh) 2017-08-02 2023-12-22 弗特克斯药品有限公司 制备吡咯烷化合物的方法
US10988454B2 (en) 2017-09-14 2021-04-27 Abbvie Overseas S.À.R.L. Modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use
WO2019071078A1 (en) 2017-10-06 2019-04-11 Proteostasis Therapeutics, Inc. COMPOUNDS, COMPOSITIONS AND METHODS FOR INCREASING CFTR ACTIVITY
CA3078893A1 (en) 2017-10-19 2019-04-25 Vertex Pharmaceuticals Incorporated Crystalline forms and compositions of cftr modulators
WO2019113089A1 (en) 2017-12-04 2019-06-13 Vertex Pharmaceuticals Incorporated Compositions for treating cystic fibrosis
JP7245834B2 (ja) 2017-12-08 2023-03-24 バーテックス ファーマシューティカルズ インコーポレイテッド 嚢胞性線維症膜コンダクタンス制御因子のモジュレーターを作成するためのプロセス
TWI810243B (zh) 2018-02-05 2023-08-01 美商維泰克斯製藥公司 用於治療囊腫纖化症之醫藥組合物
US20210009560A1 (en) 2018-03-30 2021-01-14 Vertex Pharmaceuticals Incorporated Crystalline forms of modulators of cftr
WO2019195739A1 (en) 2018-04-05 2019-10-10 Alexander Russell Abela Modulators of cystic fibrosis transmembrane conductance regulator
US11414439B2 (en) 2018-04-13 2022-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
WO2020214921A1 (en) 2019-04-17 2020-10-22 Vertex Pharmaceuticals Incorporated Solid forms of modulators of cftr
WO2020242935A1 (en) 2019-05-29 2020-12-03 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
BR112022002606A2 (pt) 2019-08-14 2022-05-03 Vertex Pharma Moduladores do regulador de condutância transmembrana da fibrose cística
TW202120517A (zh) 2019-08-14 2021-06-01 美商維泰克斯製藥公司 製備cftr調節劑之方法
TW202115092A (zh) 2019-08-14 2021-04-16 美商維泰克斯製藥公司 囊腫纖維化跨膜傳導調節蛋白之調節劑
BR112022002605A2 (pt) 2019-08-14 2022-05-03 Vertex Pharma Formas cristalinas de moduladores de cftr

Also Published As

Publication number Publication date
UY37513A (es) 2018-07-31
EP3551622A1 (en) 2019-10-16
NZ754805A (en) 2023-11-24
EP3551622B1 (en) 2020-10-07
JOP20190125A1 (ar) 2019-05-28
AU2021211993B2 (en) 2023-04-06
JOP20190125B1 (ar) 2022-03-14
SA519401947B1 (ar) 2022-06-19
ZA201904062B (en) 2022-12-21
IL277491A (en) 2020-11-30
SI3551622T1 (sl) 2021-02-26
ES2837431T3 (es) 2021-06-30
IL267048A (en) 2019-07-31
US11453655B2 (en) 2022-09-27
MA49235A (fr) 2019-10-16
CN110267948A (zh) 2019-09-20
IL294237A (en) 2022-08-01
AU2021211993A1 (en) 2021-08-26
LT3551622T (lt) 2021-02-25
ECSP19048759A (es) 2019-07-31
RS61150B1 (sr) 2020-12-31
MD3551622T2 (ro) 2021-03-31
PE20191304A1 (es) 2019-09-23
JP2020500906A (ja) 2020-01-16
JP7373522B2 (ja) 2023-11-02
JP2021119172A (ja) 2021-08-12
US10793547B2 (en) 2020-10-06
US20230357191A1 (en) 2023-11-09
UY39723A (es) 2022-05-31
CL2019001553A1 (es) 2020-04-03
GEP20247634B (en) 2024-06-25
CA3046086A1 (en) 2018-06-14
AU2017371200A1 (en) 2019-07-11
MA54847A (fr) 2021-12-08
CN117843619A (zh) 2024-04-09
MA49235B1 (fr) 2021-02-26
HUE052205T2 (hu) 2021-04-28
KR102269492B1 (ko) 2021-06-24
JP6916285B2 (ja) 2021-08-11
BR112019011626A2 (pt) 2019-10-22
WO2018107100A1 (en) 2018-06-14
IL267048B (en) 2020-11-30
CO2019007129A2 (es) 2019-07-31
KR20190101993A (ko) 2019-09-02
SG10201913606VA (en) 2020-02-27
EA201991403A1 (ru) 2019-12-30
HRP20201946T1 (hr) 2021-01-22
EP3812379A1 (en) 2021-04-28
DK3551622T3 (da) 2020-11-23
AU2017371200B2 (en) 2021-05-06
TWI774712B (zh) 2022-08-21
EA039280B1 (ru) 2021-12-28
CN110267948B (zh) 2023-12-08
PT3551622T (pt) 2020-11-12
TW201835065A (zh) 2018-10-01
MX2019006637A (es) 2019-08-21
IL277491B (en) 2022-08-01
MX2021013639A (es) 2022-09-30
EA202192783A1 (ru) 2022-02-24
US20210047295A1 (en) 2021-02-18
US20180162839A1 (en) 2018-06-14
CY1123736T1 (el) 2022-03-24
JP2023154048A (ja) 2023-10-18
UA128449C2 (uk) 2024-07-17
PE20241131A1 (es) 2024-05-24
AU2023203944A1 (en) 2023-07-13

Similar Documents

Publication Publication Date Title
AR110346A1 (es) Modulador del regulador de conductancia transmembrana de fibrosis quística, composiciones farmacéuticas, métodos de tratamiento y proceso para producir el modulador
AR114254A1 (es) Moduladores del regulador de conductancia transmembrana de fibrosis quística, composiciones farmacéuticas, métodos de tratamiento y proceso de preparación de los moduladores
AR110139A1 (es) COMPUESTOS MONO Y ESPIROCÍCLICOS QUE CONTIENEN CICLOBUTANO Y AZETIDINA COMO INHIBIDORES DE LA INTEGRINA aV
AR088175A1 (es) 3-pirimidin-4-il-oxazolidin-2-onas utiles para tratar cancer y composiciones farmaceuticas que las contienen
AR108130A1 (es) Derivados de pirazolopirimidina
AR099177A1 (es) Determinadas (2s)-n-[(1s)-1-ciano-2-feniletil]-1,4-oxazepan-2-carboxamidas como inhibidores de dipeptidil peptidasa 1
AR106865A1 (es) Piridinas sustituidas y métodos de uso
AR096979A1 (es) Derivados de pirrol, su procedimiento de preparación y las composiciones farmacéuticas que los contienen
AR077695A1 (es) Derivados de pirimidina como inhibidores del factor ixa
AR104415A1 (es) Compuestos antiestrogénicos derivados de cromeno
AR107061A1 (es) Heteroarilhidroxipirimidinonas como agonistas del receptor de apj
AR108906A1 (es) Heterociclos de biarilmetilo
AR100808A1 (es) Inhibidores de fosfatidilinositol 3-quinasa
AR103833A1 (es) Compuestos bicíclicos de sulfonamida cetona
AR100807A1 (es) Inhibidores de fosfatidilinositol 3-quinasa
AR094300A1 (es) Derivados de quinolonas
RU2016135922A (ru) Терапевтические соединения и композиции
AR090945A1 (es) Moduladores de la via del complemento y usos de los mismos
AR100806A1 (es) Inhibidores de fosfatidilinositol 3-quinasa
AR106297A1 (es) Compuestos macrocíclicos modificados como inhibidores selectivos de la quinasa cdk9
AR103742A1 (es) Derivados de trifluorometilpropanamida
AR099914A1 (es) Derivados de indol y de pirrol, su procedimiento de preparación y las composiciones farmacéuticas que los contienen
AR109952A1 (es) Derivados de fenilamina 4-sustituidos y su uso para proteger cultivos al combatir microorganismos fitopatogénicos indeseados
AR093503A1 (es) Derivados de n-(piridin-2-il)pirimidin-4-amina que contienen un grupo sulfoximina
AR106185A1 (es) Compuestos macrocíclicos de sulfondiimina