IL314404B1 - Pyrrolopyrimidines as CFTR enhancers - Google Patents
Pyrrolopyrimidines as CFTR enhancersInfo
- Publication number
- IL314404B1 IL314404B1 IL314404A IL31440424A IL314404B1 IL 314404 B1 IL314404 B1 IL 314404B1 IL 314404 A IL314404 A IL 314404A IL 31440424 A IL31440424 A IL 31440424A IL 314404 B1 IL314404 B1 IL 314404B1
- Authority
- IL
- Israel
- Prior art keywords
- pyrimidin
- pyrrolo
- fluorophenyl
- triazol
- amine
- Prior art date
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
- A61K31/495—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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
- A61P11/12—Mucolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- 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
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Otolaryngology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662423919P | 2016-11-18 | 2016-11-18 | |
| PCT/US2017/062148 WO2018094137A1 (en) | 2016-11-18 | 2017-11-17 | Pyrrolopyrimidines as cftr potentiators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL314404A IL314404A (en) | 2024-09-01 |
| IL314404B1 true IL314404B1 (en) | 2025-09-01 |
Family
ID=62144793
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL314404A IL314404B1 (en) | 2016-11-18 | 2017-11-17 | Pyrrolopyrimidines as CFTR enhancers |
| IL296279A IL296279A (en) | 2016-11-18 | 2017-11-17 | Pyrrolopyrimidines as cftr enhancers |
| IL266668A IL266668B2 (en) | 2016-11-18 | 2019-05-15 | Pyrrolopyrimidines as cftr enhancers |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL296279A IL296279A (en) | 2016-11-18 | 2017-11-17 | Pyrrolopyrimidines as cftr enhancers |
| IL266668A IL266668B2 (en) | 2016-11-18 | 2019-05-15 | Pyrrolopyrimidines as cftr enhancers |
Country Status (22)
| Country | Link |
|---|---|
| US (5) | US10301315B2 (enExample) |
| EP (2) | EP3541390B1 (enExample) |
| JP (3) | JP6978507B2 (enExample) |
| KR (2) | KR102824092B1 (enExample) |
| CN (2) | CN110337294B (enExample) |
| AU (2) | AU2017362350B2 (enExample) |
| CA (1) | CA3044050A1 (enExample) |
| CL (1) | CL2019001334A1 (enExample) |
| CO (1) | CO2019005993A2 (enExample) |
| CR (1) | CR20190292A (enExample) |
| DO (1) | DOP2019000126A (enExample) |
| EC (1) | ECSP19043120A (enExample) |
| ES (1) | ES2983686T3 (enExample) |
| IL (3) | IL314404B1 (enExample) |
| MX (2) | MX2021012639A (enExample) |
| PE (1) | PE20200739A1 (enExample) |
| PH (1) | PH12019501098A1 (enExample) |
| PL (1) | PL3541390T3 (enExample) |
| RU (2) | RU2021129721A (enExample) |
| SG (1) | SG10202106949XA (enExample) |
| UA (1) | UA125400C2 (enExample) |
| WO (1) | WO2018094137A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX350788B (es) | 2012-01-06 | 2017-09-13 | Abide Therapeutics Inc | Compuestos de carbamato y preparación y uso de los mismos. |
| SG10201902963PA (en) | 2014-10-06 | 2019-05-30 | Vertex Pharma | Modulators of cystic fibrosis transmembrane conductance regulator |
| CA3009339A1 (en) * | 2015-12-22 | 2017-06-29 | Proteostasis Therapeutics, Inc. | Methods of treating pulmonary diseases and disorders |
| GEP20217329B (en) | 2016-09-30 | 2021-12-10 | Vertex Pharma | Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator |
| PE20200739A1 (es) * | 2016-11-18 | 2020-07-24 | Cystic Fibrosis Found Therapeutics Inc | Pirrolopirimidinas como potenciadores de cftr |
| HUE052205T2 (hu) | 2016-12-09 | 2021-04-28 | Vertex Pharma | Cisztás fibrózis transzmembrán vezetõképesség szabályzó modulátora, gyógyszerészeti készítmények, kezelési eljárások és eljárás a modulátor elõállítására |
| SG10201911076QA (en) | 2016-12-16 | 2020-01-30 | Cystic Fibrosis Found | Bycyclic heteroaryl derivatives as cftr potentiators |
| BR112019025801A2 (pt) | 2017-06-08 | 2020-07-07 | Vertex Pharmaceuticals Incorporated | métodos de tratamento para fibrose cística |
| BR112020000941A2 (pt) | 2017-07-17 | 2020-07-21 | Vertex Pharmaceuticals Incorporated | métodos de tratamento para fibrose cística |
| US11434201B2 (en) | 2017-08-02 | 2022-09-06 | Vertex Pharmaceuticals Incorporated | Processes for preparing pyrrolidine compounds |
| CA3078893A1 (en) | 2017-10-19 | 2019-04-25 | Vertex Pharmaceuticals Incorporated | Crystalline forms and compositions of cftr modulators |
| CA3085006A1 (en) | 2017-12-08 | 2019-06-13 | Vertex Pharmaceuticals Incorporated | Processes for making modulators of cystic fibrosis transmembrane conductance regulator |
| 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 |
| HRP20230030T1 (hr) | 2018-02-15 | 2023-03-03 | Vertex Pharmaceuticals Incorporated | Makrocikli kao modulatori regulatora provodljivosti transmembrane cistične fibroze, njihovi farmaceutski pripravci, njihova uporaba u liječenju cistične fibroze, i postupak za njihovu proizvodnju |
| EP3774825A1 (en) | 2018-04-13 | 2021-02-17 | 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 |
| BR112021024668A2 (pt) * | 2019-06-10 | 2022-05-31 | Novartis Ag | Derivado de piridina e pirazina para o tratamento de fc, dpoc e bronquiectasia |
| JP2022541178A (ja) | 2019-07-15 | 2022-09-22 | ノバルティス アーゲー | （ｓ）－３－アミノ－６－メトキシ－ｎ－（３，３，３－トリフルオロ－２－ヒドロキシ－２－メチルプロピル）－５－（トリフルオロメチル）ピコリンアミド製剤 |
| HUE066896T2 (hu) | 2019-08-14 | 2024-09-28 | Vertex Pharma | Eljárás CFTR modulátorok elõállítására |
| CA3150162A1 (en) | 2019-08-14 | 2021-02-18 | Vertex Pharmaceuticals Incorporated | Crystalline forms of cftr modulators |
| TWI867024B (zh) | 2019-08-14 | 2024-12-21 | 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 |
| CN111138439B (zh) * | 2020-01-17 | 2021-06-25 | 厦门大学 | 氟代吡咯并嘧啶类化合物及其制备方法和应用 |
| US20230192700A1 (en) | 2020-03-06 | 2023-06-22 | Bayer Aktiengesellschaft | Pyrazolopyrazines acting on cancers via inhibition of cdk12 |
| CN116033895A (zh) | 2020-08-20 | 2023-04-28 | 小利兰·斯坦福大学托管委员会 | 用于治疗以黏液分泌过多为特征的呼吸系统疾病的方法 |
| WO2022125826A1 (en) | 2020-12-10 | 2022-06-16 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| WO2024096629A1 (ko) * | 2022-11-02 | 2024-05-10 | 일동제약 주식회사 | Cftr 조절제 화합물을 포함하는 점안용 조성물 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994013676A1 (en) * | 1992-12-17 | 1994-06-23 | Pfizer Inc. | Pyrrolopyrimidines as crf antagonists |
| NZ518726A (en) | 2001-05-09 | 2004-06-25 | Warner Lambert Co | Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor |
| JP2004534779A (ja) | 2001-05-30 | 2004-11-18 | エルジー ライフサイエンス リミテッド | 疾病治療用プロテインキナーゼ阻害剤 |
| US20050008640A1 (en) * | 2003-04-23 | 2005-01-13 | Wendy Waegell | Method of treating transplant rejection |
| CA2553724A1 (en) * | 2004-02-03 | 2005-08-18 | Abbott Laboratories | Aminobenzoxazoles as therapeutic agents |
| ES2545907T3 (es) | 2005-12-29 | 2015-09-16 | Abbvie Inc. | Inhibidores de proteína quinasa |
| KR20090007319A (ko) * | 2006-03-11 | 2009-01-16 | 베르날리스 (알 앤드 디) 리미티드 | Ｈｓｐ90 억제제로서 사용되는 피롤로피리미딘 유도체 |
| KR20150038395A (ko) * | 2006-04-04 | 2015-04-08 | 더 리젠트스 오브 더 유니이버시티 오브 캘리포니아 | 키나제 길항물질 |
| CA2705303A1 (en) * | 2007-11-07 | 2009-05-14 | Foldrx Pharmaceuticals, Inc. | Modulation of protein trafficking |
| EA024252B1 (ru) | 2009-01-08 | 2016-08-31 | Кьюрис, Инк. | Ингибиторы фосфоинозитид-3-киназ с цинксвязывающей группой |
| US20130123281A1 (en) | 2011-11-11 | 2013-05-16 | Beta Cat Pharmaceuticals, Llc | Compositions and Methods for Inhibition of TBL-1 Binding to Disease-Associated Molecules |
| US8828998B2 (en) * | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| WO2014060431A1 (en) * | 2012-10-16 | 2014-04-24 | Almirall, S.A. | Pyrrolotriazinone derivatives as pi3k inhibitors |
| WO2015091532A1 (en) | 2013-12-19 | 2015-06-25 | Almirall, S.A. | Pyrrolopyrimidine derivatives as pi3k inhibitors |
| PE20200739A1 (es) | 2016-11-18 | 2020-07-24 | Cystic Fibrosis Found Therapeutics Inc | Pirrolopirimidinas como potenciadores de cftr |
-
2017
- 2017-11-17 PE PE2019001045A patent/PE20200739A1/es unknown
- 2017-11-17 WO PCT/US2017/062148 patent/WO2018094137A1/en not_active Ceased
- 2017-11-17 RU RU2021129721A patent/RU2021129721A/ru unknown
- 2017-11-17 ES ES17872726T patent/ES2983686T3/es active Active
- 2017-11-17 MX MX2021012639A patent/MX2021012639A/es unknown
- 2017-11-17 CN CN201780083801.0A patent/CN110337294B/zh active Active
- 2017-11-17 IL IL314404A patent/IL314404B1/en unknown
- 2017-11-17 RU RU2019118623A patent/RU2757457C2/ru active
- 2017-11-17 EP EP17872726.9A patent/EP3541390B1/en active Active
- 2017-11-17 JP JP2019547579A patent/JP6978507B2/ja active Active
- 2017-11-17 US US15/815,809 patent/US10301315B2/en active Active
- 2017-11-17 EP EP24170395.8A patent/EP4424311A3/en active Pending
- 2017-11-17 UA UAA201906838A patent/UA125400C2/uk unknown
- 2017-11-17 IL IL296279A patent/IL296279A/en unknown
- 2017-11-17 PL PL17872726.9T patent/PL3541390T3/pl unknown
- 2017-11-17 CA CA3044050A patent/CA3044050A1/en active Pending
- 2017-11-17 MX MX2019005822A patent/MX387203B/es unknown
- 2017-11-17 AU AU2017362350A patent/AU2017362350B2/en active Active
- 2017-11-17 KR KR1020237033420A patent/KR102824092B1/ko active Active
- 2017-11-17 CN CN202211239693.0A patent/CN115850268B/zh active Active
- 2017-11-17 CR CR20190292A patent/CR20190292A/es unknown
- 2017-11-17 KR KR1020197017510A patent/KR102585398B1/ko active Active
- 2017-11-17 SG SG10202106949XA patent/SG10202106949XA/en unknown
-
2019
- 2019-04-05 US US16/377,005 patent/US10494374B2/en active Active
- 2019-05-15 IL IL266668A patent/IL266668B2/en unknown
- 2019-05-16 PH PH12019501098A patent/PH12019501098A1/en unknown
- 2019-05-16 CL CL2019001334A patent/CL2019001334A1/es unknown
- 2019-05-17 DO DO2019000126A patent/DOP2019000126A/es unknown
- 2019-06-07 CO CONC2019/0005993A patent/CO2019005993A2/es unknown
- 2019-06-17 EC ECSENADI201943120A patent/ECSP19043120A/es unknown
- 2019-09-20 US US16/578,277 patent/US20200017512A1/en not_active Abandoned
-
2021
- 2021-02-18 US US17/179,062 patent/US20210171534A1/en not_active Abandoned
- 2021-11-10 JP JP2021183048A patent/JP7360434B2/ja active Active
-
2022
- 2022-03-16 AU AU2022201816A patent/AU2022201816B2/en active Active
-
2023
- 2023-04-13 US US18/134,455 patent/US20230250100A1/en active Pending
- 2023-09-29 JP JP2023169299A patent/JP7592814B2/ja active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2022201816B2 (en) | Pyrrolopyrimidines as CFTR potentiators | |
| AU2021277702B2 (en) | Bicyclic heteroaryl derivatives as CFTR potentiators | |
| HK40014108A (en) | Pyrrolopyrimidines as cftr potentiators | |
| HK40014108B (en) | Pyrrolopyrimidines as cftr potentiators | |
| BR122022008825B1 (pt) | Compostos pirrolopirimidinas potenciadores de cftr, composição farmacêutica que compreende os mesmos e usos terapêuticos dos ditos compostos e composição | |
| BR112019010167B1 (pt) | Compostos pirrolopirimidinas potenciadores de cftr | |
| BR122024011694A2 (pt) | Compostos derivados de heteroarila bicíclica como potenciadores de cftr, composição farmacêutica que compreende os mesmos e uso dos ditos compostos para tratar fibrose cística, asma, bronquiectasia, doença pulmonar obstrutiva crônica, constipação, diabetes mellitus, doença do olho seco, pancreatite, rinossinusite ou síndrome de sjogren | |
| BR112019012335B1 (pt) | Compostos derivados de heteroarila bicíclica como potenciadores de cftr, composição farmacêutica que compreende os mesmos e uso dos ditos compostos para tratar fibrose cística, asma, bronquiectasia, doença pulmonar obstrutiva crônica, constipação, diabetes mellitus, doença do olho seco, pancreatite, rinossinusite ou síndrome de sjogren |