RU2019104161A - Композиции для лечения легочного фиброза - Google Patents
Композиции для лечения легочного фиброза Download PDFInfo
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- RU2019104161A RU2019104161A RU2019104161A RU2019104161A RU2019104161A RU 2019104161 A RU2019104161 A RU 2019104161A RU 2019104161 A RU2019104161 A RU 2019104161A RU 2019104161 A RU2019104161 A RU 2019104161A RU 2019104161 A RU2019104161 A RU 2019104161A
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- Prior art keywords
- pulmonary fibrosis
- subject
- independently
- compound
- risk
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- 208000005069 pulmonary fibrosis Diseases 0.000 title claims 15
- 239000000203 mixture Substances 0.000 title 1
- 238000000034 method Methods 0.000 claims 11
- 150000001875 compounds Chemical class 0.000 claims 8
- -1 hydroxy, amino Chemical group 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 6
- 239000012453 solvate Substances 0.000 claims 6
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 0.000 claims 4
- 229920006395 saturated elastomer Polymers 0.000 claims 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 230000000069 prophylactic effect Effects 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010011224 Cough Diseases 0.000 claims 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 206010021143 Hypoxia Diseases 0.000 claims 1
- 208000032376 Lung infection Diseases 0.000 claims 1
- 206010035664 Pneumonia Diseases 0.000 claims 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- 150000003973 alkyl amines Chemical class 0.000 claims 1
- 239000010425 asbestos Substances 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000000428 dust Substances 0.000 claims 1
- 239000000835 fiber Substances 0.000 claims 1
- 239000007789 gas Substances 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 230000007954 hypoxia Effects 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 201000004193 respiratory failure Diseases 0.000 claims 1
- 229910052895 riebeckite Inorganic materials 0.000 claims 1
- 239000000779 smoke Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/402—1-aryl substituted, e.g. piretanide
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- A61K31/426—1,3-Thiazoles
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- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
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- C07D263/36—One oxygen atom
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- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
- C07D263/44—Two oxygen atoms
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- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
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- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D277/62—Benzothiazoles
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- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
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Claims (65)
1. Соединение формулы:
или его фармакологически приемлемые соль, стереоизомер, диастереомер, энантиомер, рацемат, гидрат и/или сольват,
где:
В выбран из группы, состоящей из:
R1, R3 и R4 независимо представляют собой С, СН, СН2, О, N, NH или S;
R2 представляет собой С, СН, СН2, N, NH, C-CF3, CH-CF3 или С=O;
R5-R9 независимо представляют собой С или N;
Q независимо выбран из галогена, алкила, гидрокси, амино и замещенного амино;
n равно 0, 1, 2, 3, 4 или 5;
D представляет собой:
R10-R14 независимо представляют собой С, N, О или S;
Т независимо выбран из С1-6алкила, галогена, С0-6алкилкарбоновой кислоты, амино, гидрокси и С1-6алкокси; и
m равно 0, 1, 2, 3 или 4,
при этом D не может представлять собой незамещенный фенил, и Q не может представлять собой гидрокси, когда n равно 1, и все R5-R9 представляют собой С.
2. Соединение по п. 1, где соединение выбрано из группы, состоящей из:
или их фармакологически приемлемых соли, стереоизомера, диастереомера, энантиомера, рацемата, гидрата и/или сольвата.
3. Соединение формулы:
или его фармакологически приемлемые соль, стереоизомер, диастереомер, энантиомер, рацемат, гидрат и/или сольват.
4. Способ профилактического или терапевтического лечения легочного фиброза или связанного с ним состояния у субъекта с легочным фиброзом или с риском развития легочного фиброза, включающий введение субъекту эффективного количества соединения по любому из пп. 1-3.
5. Способ профилактического или терапевтического лечения легочного фиброза или связанного с ним состояния у субъекта с легочным фиброзом или с риском развития легочного фиброза, включающий введение субъекту эффективного количества соединения формул:
или его фармакологически приемлемых соли, стереоизомера, диастереомера, энантиомера, рацемата, гидрата и/или сольвата,
где:
А выбран из возможно замещенного насыщенного, частично насыщенного или ненасыщенного 5- или 6-членного гетероциклила; возможно замещенного С1-6алкоксиламина; возможно замещенного С1-6алкиламина; возможно замещенной С0-6алкилкарбоновой кислоты; возможно замещенного С1-6алкилгидроксила; возможно замещенного насыщенного или ненасыщенного бициклического С0-6алкилгетероциклила; и возможно замещенного насыщенного или ненасыщенного бициклического С1-6алкоксил-гетероциклила;
В выбран из группы, состоящей из:
Q независимо выбран из галогена, алкила, гидрокси, амино и замещенного амино;
n равно 0, 1, 2, 3, 4 или 5;
R1, R3 и R4 независимо представляют собой С, СН, СН2, О, N, NH или S;
R2 представляет собой С, СН, СН2, N, NH, C-CF3, CH-CF3 или С=O;
R5-R9 независимо представляют собой С или N;
D представляет собой:
R10-R14 независимо представляют собой С, N, О или S;
Т независимо выбран из С1-6алкила, галогена, С0-6алкилкарбоновой кислоты, амино, гидрокси и С1-6алкокси;
m равно 0, 1, 2, 3 или 4; и
6. Способ по п. 5, где соединение выбрано из группы, состоящей из:
или их фармакологически приемлемых соли, стереоизомера, диастереомера, энантиомера, рацемата, гидрата и/или сольвата.
7. Способ по любому из пп. 4-6, где субъект с риском развития легочного фиброза подвергался воздействию газов, дыма, химических веществ, асбестовых волокон или пыли.
8. Способ по любому из пп. 4-6, где субъект с риском развития легочного фиброза имеет аутоиммунное расстройство, вирусную инфекцию или бактериальную инфекцию легкого.
9. Способ по любому из пп. 4-6, где субъект с риском развития легочного фиброза получал лучевую терапию по поводу рака легкого или молочной железы.
10. Способ по любому из пп. 4-6, где субъект с риском развития легочного фиброза имеет генетическую предрасположенность.
11. Способ по любому из пп. 4-6, где субъект с риском развития легочного фиброза является курильщиком.
12. Способ по любому из пп. 4-11, где связанное с легочным фиброзом состояние выбрано из легочной гипертензии, правосторонней сердечной недостаточности, дыхательной недостаточности, гипоксии, кашля, образования тромбов, пневмонии и рака легкого.
13. Способ по любому из пп. 4-12, где такое лечение предотвращает, ослабляет или замедляет прогрессирование легочного фиброза.
14. Способ по любому из пп. 4-13, где такое лечение ослабляет диагностированный легочный фиброз.
15. Соединение формулы
или его фармакологически приемлемые соль, стереоизомер, диастереомер, энантиомер, рацемат, гидрат и/или сольват.
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PCT/AU2017/050784 WO2018018091A1 (en) | 2016-07-28 | 2017-07-28 | Compositions for the treatment of pulmonary fibrosis |
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