US2013095181A1PendingUtilityA1
Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyriodin-2-yl)benzoic acid and administration thereof
Est. expiryApr 7, 2030(~3.7 yrs left)· nominal 20-yr term from priority
Inventors:Marinus Jacobus VerwijsRossitza Gueorguieva AlargovaRitu Rohit KaushikIrina Nikolaevna KadiyalaChristopher R. Young
A61P 3/06A61P 7/12A61P 7/04A61P 3/10A61P 5/14A61P 35/00A61P 37/02A61P 9/00A61P 43/00A61P 5/18A61P 7/00A61P 25/28A61P 25/16A61P 27/02A61P 25/08A61P 25/14A61P 25/02A61P 25/00A61P 21/00A61P 11/06A61P 13/12A61P 13/02A61P 15/10A61P 19/00A61P 11/02A61P 1/16A61P 11/00A61P 1/18A61P 19/08A61P 19/10A61P 15/00A61P 21/02A61P 1/10A61P 21/04A61K 31/443A61K 9/2077C07D 405/14A61K 9/2054A61K 9/2027A61K 9/2866A61K 31/47C07D 405/12A61K 9/2013A61K 9/2095A61K 9/28A61K 9/1652A61K 9/141A61K 9/1623A61K 9/1682C07D 451/02A61K 9/2009A61K 9/0053A61K 45/06
61
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Claims
Abstract
A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.
Claims
exact text as granted — not AI-modified1 . A tablet for oral administration comprising:
a. Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A; b. a filler; c. a diluent; d. a disintegrant; e. a surfactant; f. a lubricant; and g. at least one of a binder and a glidant.
2 . The tablet of claim 1 , wherein Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A is present in the tablet in an amount ranging from about 25 mg to about 250 mg.
3 . The tablet of claim 1 or 2 , wherein the amount of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A in the tablet ranges from about 15 wt % to about 75 wt % by weight of the tablet, or from about 20 wt % to about 45 wt % by weight of the tablet, from about 40 wt % to about 60 wt % by weight of the tablet.
4 . (canceled)
5 . (canceled)
6 . The tablet of claim 1 , wherein the filler is selected from cellulose, modified cellulose, sodium carboxymethyl cellulose, ethyl cellulose hydroxymethyl cellulose, hydroxypropylcellulose, cellulose acetate, microcrystalline cellulose, dibasic calcium phosphate, sucrose, lactose, corn starch, potato starch, or any combination thereof.
7 . The tablet of claim 6 , wherein the filler is microcrystalline cellulose (MCC) and is present in the tablet in an amount ranging from about 20 wt % to about 50 wt % by weight of the tablet.
8 . The tablet of claim 1 , wherein the diluent is selected from lactose, mannitol, sorbitol, cellulose, calcium phosphate, starch, sugar or any combination thereof.
9 . The tablet of claim 8 , wherein the diluent is mannitol and is present in the tablet in an amount ranging from about 1 wt % to about 30 wt % by weight of the tablet.
10 . The tablet of claim 1 , wherein the disintegrant is selected from agar-agar, algins, calcium carbonate, carboxmethylcellulose, cellulose, hydroxypropylcellulose, low substituted hydroxypropylcellulose, clays, croscarmellose sodium, crospovidone, gums, magnesium aluminum silicate, methylcellulose, polacrilin potassium, sodium alginate, sodium starch glycolate, maize starch, potato starch, tapioca starch, or any combination thereof.
11 . The tablet of claim 10 , wherein the disintegrant is croscarmellose sodium and is present in the tablet at a concentration of 5 wt % or less by weight of the tablet.
12 . The tablet of claim 1 , wherein the surfactant is selected from sodium lauryl sulfate, sodium stearyl fumerate, polyoxyethylene 20 sorbitan mono-oleate, or any combination thereof.
13 . The tablet of claim 12 , wherein the surfactant is sodium lauryl sulfate and has a concentration of about 5 wt % or less by weight of the tablet.
14 . The tablet of claim 1 , wherein the glidant is selected from colloidal silicon dioxide, talc, corn starch, or a combination thereof.
15 . The tablet of claim 14 , wherein the glidant is colloidal silicon dioxide and has a concentration of 5 wt % or less by weight of the tablet.
16 . The tablet of claim 1 , wherein the binder is selected from polyvinylpyrrolidone, dibasic calcium phosphate, sucrose, corn starch, modified cellulose, or any combination thereof.
17 . The tablet of claim 16 , wherein the binder is polyvinylpyrrolidone and has a concentration of less than 10 wt % by weight of the tablet.
18 . The tablet of claim 1 , wherein the lubricant is selected from magnesium stearate, calcium stearate, zinc stearate, sodium stearate, stearic acid, aluminum stearate, leucine, glyceryl behenate, hydrogenated vegetable oil or any combination thereof.
19 . The tablet of claim 18 , wherein the lubricant is magnesium stearate and has a concentration of less than 5 wt % by weight of the tablet.
20 . The tablet of claim 1 , wherein the tablet further comprises a colorant.
21 . A pharmaceutical composition comprising a plurality of granules, the composition comprising:
a. Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A in an amount ranging from about 20 wt % to about 80 wt % by weight of the composition; b. a filler in an amount ranging from about 20 wt % to about 50 wt % by weight of the composition of a filler; c. a disintegrant in an amount ranging from a from about 1 wt % to about 5 wt % by weight of the composition; d. a surfactant in an amount ranging from about 2 wt % to about 0.3 wt % by weight of the composition; e. a diluent in an amount ranging from about 1 wt % to about 30 wt % by weight of the composition; f. a lubricant in an amount ranging from about 0.3 wt % to about 5 wt % by weight of the composition; and g. at least one of a binder in an amount from about 20 wt % to about 45 wt % by weight of the composition or a glidant in an amount ranging from about 0.05 wt % to about 2 wt % by weight of the composition.
22 . The tablet of claim 1 comprising:
a. Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A in an amount ranging from about 25 mg to about 250 mg;
b. a filler;
c. a diluent;
d. a disintegrant;
e. a surfactant;
f. a lubricant; and
g. at least one of a binder and a glidant.
23 . The tablet of claim 1 of one the following formulations:
(% w/w)
Roller Compaction Granule Blend
Compound 1 Form I
30
Microcrystalline cellulose
42.3
Mannitol
21.2
Croscarmellose Sodium
3
Sodium Lauryl Sulfate
1
Colloidal Silica
0.5
Magnesium Stearate
2
Tablet Composition
(100 mg dose, 335 mg image)
Roller Compaction Granule Blend
99.5
Magnesium Stearate
0.5
(% w/w)
High Shear Granule Blend
Compound 1 Form I
50
Microcrystalline cellulose
30
Mannitol
13
Croscarmellose Sodium
2
Polyvinylpyrrolidone
4
Sodium Lauryl Sulfate
1
Water (removed during drying)
25-40%
solids
Tablet Composition
(100 mg dose, 205 mg image)
High Shear Granule Blend
97.5
Croscarmellose Sodium
2.0
Magnesium Stearate
0.5
(% w/w)
High Shear Granule Blend
Compound 1 Form I
60
Microcrystalline cellulose
20
Mannitol
13
Croscarmellose Sodium
2
Polyvinylpyrrolidone
4
Sodium Lauryl Sulfate
1
Water (removed during drying)
25-40%
solids
Tablet Composition
(100 mg dose, 171 mg image)
High Shear Granule Blend
97.5
Croscarmellose Sodium
2.0
Magnesium Stearate
0.5
(% w/w)
High Shear Granule Blend
Compound 1 Form I
60
Microcrystalline cellulose
20
Mannitol
13
Croscarmellose Sodium
2
Polyvinylpyrrolidone
4
Sodium Lauryl Sulfate
1
Water (removed during drying)
25-40%
solids
Tablet Composition
(200 mg dose, 402 mg image)
High Shear Granule Blend
83
Microcrystalline cellulose
14
Croscarmellose Sodium
2
Magnesium Stearate
1.0
mg
High Shear Granule Blend
Compound 1 Form I
200
Microcrystalline cellulose
66
Mannitol
43
Croscarmellose Sodium
7
Polyvinylpyrrolidone
13
Sodium Lauryl Sulfate
3
Core Tablet Composition
(200 mg dose, 400 mg image)
High Shear Granule Blend
332
Microcrystalline cellulose
56
Croscarmellose Sodium
8
Magnesium Stearate
4
Film Coated Tablet
(200 mg dose, 412 mg image)
Core Tablet Composition
400
Film Coat
12
Wax
0.04
mg
High Shear Granule Blend
Compound 1 Form I
200
Microcrystalline cellulose
67
Mannitol
45
Croscarmellose Sodium
7
Polyvinylpyrrolidone
10.4
Sodium Lauryl Sulfate
2.6
Core Tablet Composition
(200 mg dose, 400 mg image)
High Shear Granule Blend
332
Microcrystalline cellulose
56
Croscarmellose Sodium
8
Magnesium Stearate
4
Film Coated Tablet
(200 mg dose, 412 mg image)
Core Tablet Composition
400
Film Coat
12
Wax
0.04
(% w/w)
High Shear Granule Blend
Compound 1 Form I
70
Microcrystalline cellulose
12
Mannitol
11
Croscarmellose Sodium
2
Polyvinylpyrrolidone
4
Sodium Lauryl Sulfate
1
Water (removed during drying)
25-40%
solids
Tablet Composition
(100 mg dose, 147 mg image)
High Shear Granule Blend
97.5
Croscarmellose Sodium
2.0
Magnesium Stearate
0.5
(% w/w)
High Shear Granule Blend
Compound 1 Form I or Form II
61
Microcrystalline cellulose
20.3
Mannitol
13.2
Croscarmellose Sodium
2
Polyvinylpyrrolidone
2.7
Sodium Lauryl Sulfate
0.7
Tablet Composition
(100 mg dose, 197 mg image)
High Shear Granule Blend
83
Microcrystalline cellulose
14
Croscarmellose Sodium
2
Magnesium Stearate
1
mg
High Shear Granule Blend
Compound 1 Form I or Form II
100
Microcrystalline cellulose
33.3
Mannitol
21.7
Croscarmellose Sodium
3.3
Polyvinylpyrrolidone
4.4
Sodium Lauryl Sulfate
1.1
Core Tablet Composition
(100 mg dose, 197 mg image)
High Shear Granule Blend
163.9
Microcrystalline cellulose
27.6
Croscarmellose Sodium
3.9
Magnesium Stearate
2.0
24 . (canceled)
25 . (canceled)
26 . (canceled)
27 . (canceled)
28 . (canceled)
29 . (canceled)
30 . (canceled)
31 . (canceled)
32 . The pharmaceutical composition of claim 21 which is suitable for oral administration comprising:
a. Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A in an amount ranging from about 20 wt % to about 80 wt % by weight of the composition;
b. a filler comprising microcrystalline cellulose in an amount ranging from about 20 wt % to about 50 wt % by weight of the composition;
c. a disintegrant comprising sodium croscarmellose sodium in an amount ranging from about 1 wt % to about 5 wt % by weight of the composition;
d. a surfactant comprising sodium lauryl sulfate in an amount ranging from about 2 wt % to about 0.3 wt % by weight of the composition;
e. a diluent comprising mannitol in an amount ranging from about 1 wt % to about 30 wt % by weight of the composition;
f. a lubricant comprising magnesium stearate in an amount ranging from about 0.3 wt % to about 5 wt % by weight of the composition; and
g. at least one of: a binder comprising polyvinylpyrrolidone in an amount ranging from about 0.1 wt % to about 5 wt % by weight of the composition and a glidant comprising colloidal silica in an amount ranging from about 0.05 wt % to about 2 wt % by weight of the composition.
33 . The pharmaceutical composition of claim 32 , further comprising about 0.4 wt % of colorant by weight of the composition.
34 . The pharmaceutical composition of claim 32 , wherein the pharmaceutical composition comprises a plurality of granules, wherein the plurality of granules have a mean or average particle diameter ranging from 100 μm to about 2 mm.
35 . (canceled)
36 . The pharmaceutical composition of claim 32 , wherein the pharmaceutical composition is a tablet comprising a coating.
37 . (canceled)
38 . The pharmaceutical composition of claim 32 , wherein the pharmaceutical composition further comprises at least one additional therapeutic agent, wherein the additional therapeutic agent is a CFTR modulator or a CFTR potentiator.
39 . (canceled)
40 . (canceled)
41 . A dosage unit form which comprises:
a. about 30 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A by weight of the composition; b. about 42 wt % of microcrystalline cellulose by weight of the composition; c. about 21 wt % of mannitol by weight of the composition; d. about 3 wt % of sodium croscarmellose sodium by weight of the composition; e. about 1 wt % of sodium lauryl sulfate by weight of the composition; f. about 2.5 wt % of magnesium stearate by weight of the composition; and g. about 0.5 wt % of colloidal silica by weight of the composition; a. about 50 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A; b. about 30 wt % of microcrystalline cellulose by weight of the composition; c. about 13 wt % of mannitol by weight of the composition; d. about 2 wt % of sodium croscarmellose sodium by weight of the composition; e. about 4 wt % of polyvinylpyrrolidone by weight of the composition; f. about 1 wt % of sodium lauryl sulfate by weight of the composition; and g. about 0.5 wt % of magnesium stearate by weight of the composition; a. about 60 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A; b. about 20 wt % of microcrystalline cellulose by weight of the composition; c. about 13 wt % of mannitol by weight of the composition; d. about 2 wt % of sodium croscarmellose sodium by weight of the composition; e. about 4 wt % of polyvinylpyrrolidone by weight of the composition; f. about 1 wt % of sodium lauryl sulfate by weight of the composition; and g. about 0.5 wt % of magnesium stearate by weight of the composition; a. about 60 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A; b. about 34 wt % of microcrystalline cellulose by weight of the composition; c. about 13 wt % of mannitol by weight of the composition; d. about 4 wt % of sodium croscarmellose sodium by weight of the composition; e. about 4 wt % of polyvinylpyrrolidone by weight of the composition; f. about 1 wt % of sodium lauryl sulfate by weight of the composition; and g. about 1.5 wt % of magnesium stearate by weight of the composition; a. about 150 to 250 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A; b. about 40 to 50 mg of mannitol; c. about 120 to 130 mg of microcrystalline cellulose; d. about 10 to 20 mg of croscarmellose sodium; e. about 10 to 20 mg of polyvinylpyrrolidone; f. about 1 to 5 mg of sodium lauryl sulfate; and g. about 1 to 5 mg of magnesium stearate; a. about 200 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A; b. about 43 mg of mannitol; c. about 123 mg of microcrystalline cellulose; d. about 15 mg of croscarmellose sodium; e. about 13 mg of polyvinylpyrrolidone; f. about 3 mg of sodium lauryl sulfate; and g. about 4 mg of magnesium stearate;
or
a. about 70 wt % of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or
Compound 1 HCl Salt Form A;
b. about 12 wt % of microcrystalline cellulose by weight of the composition;
c. about 11 wt % of mannitol by weight of the composition;
d. about 2 wt % of sodium croscarmellose sodium by weight of the composition;
e. about 4 wt % of polyvinylpyrrolidone by weight of the composition;
f. about 1 wt % of sodium lauryl sulfate by weight of the composition; and
g. about 0.5 wt % of magnesium stearate by weight of the composition.
42 . (canceled)
43 . (canceled)
44 . (canceled)
45 . (canceled)
46 . (canceled)
47 . (canceled)
48 . The tablet, pharmaceutical composition, or dosage unit form of claim 1 , 21 , or 41 , wherein Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A has a particle size of 0.1 microns to 50 microns, 0.1 to 20 microns, 0.1 to 10 microns, 1.0 to 5 microns, or a particle size D50 of 2.0 microns.
49 . (canceled)
50 . (canceled)
51 . (canceled)
52 . (canceled)
53 . A method of producing a pharmaceutical composition comprising the steps of: combining a therapeutically effective amount of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A and at least one granulation excipient selected from the group consisting of: a binder; a glidant; a surfactant; a lubricant; a disintegrant; a filler, a diluent and combinations thereof to form an admixture; mixing the admixture; and compacting the admixture to form the pharmaceutical composition.
54 . The method of claim 53 , wherein the pharmaceutical composition comprises a plurality of granules.
55 . The method of claim 53 , wherein compacting the admixture comprises compacting the admixture in a roller compactor forming compressed sheets of admixture; and milling the sheets of admixture to form a plurality of granules.
56 . The method of claim 54 , further comprising compressing the plurality of granules with at least one pharmaceutical acceptable excipient to form a tablet, wherein the at least one pharmaceutical acceptable excipient is selected from the group consisting of magnesium stearate, croscarmellose sodium and combinations thereof.
57 . (canceled)
58 . The method according to claim 54 , wherein the plurality of granules are compressed to produce a tablet having a hardness of at least 5 kP.
59 . The method of claim 53 , wherein the step of compacting the admixture to form the pharmaceutical composition further comprises drying the admixture.
60 . The method of claim 53 , wherein mixing the admixture comprises mixing the admixture until the admixture is substantially homogenous.
61 . The method of claim 53 , wherein a plurality of granules are formed by combining Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A with a granulation fluid comprising a surfactant and a binder.
62 . The method of claim 61 , wherein the surfactant is sodium lauryl sulfate.
63 . A method of administering a tablet comprising orally administering to a patient at least once per day a tablet comprising:
a. about 25 to 200 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A; b. a filler; c. a diluent; d. a disintegrant; e. a surfactant; f. at least one of a binder and a glidant; and g. a lubricant.
64 . The method of claim 63 , wherein the tablet comprises about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A.
65 . (canceled)
66 . (canceled)
67 . (canceled)
68 . (canceled)
69 . The method of claim 63 , wherein the tablet is orally administered to the patient twice per day.
70 . The method of claim 69 , wherein the tablet comprises about 25 mg about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A.
71 . (canceled)
72 . (canceled)
73 . (canceled)
74 . (canceled)
75 . (canceled)
76 . The method of claim 63 , wherein the tablet is orally administered to the patient once every 12 hours.
77 . The method of claim 76 , wherein the tablet comprises about 25 mg about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A.
78 . (canceled)
79 . (canceled)
80 . (canceled)
81 . (canceled)
82 . (canceled)
83 . A method of treating or lessening the severity of a disease in a subject comprising administering to the subject a tablet, pharmaceutical composition, or dosage unit form of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A, wherein the disease is selected from cystic fibrosis, asthma, smoke induced COPD, chronic bronchitis, rhinosinusitis, constipation, pancreatitis, pancreatic insufficiency, male infertility caused by congenital bilateral absence of the vas deferens (CBAVD), mild pulmonary disease, idiopathic pancreatitis, allergic bronchopulmonary aspergillosis (ABPA), liver disease, hereditary emphysema, hereditary hemochromatosis, coagulation-fibrinolysis deficiencies, protein C deficiency, Type 1 hereditary angioedema, lipid processing deficiencies, familial hypercholesterolemia, Type 1 chylomicronemia, abetalipoproteinemia, lysosomal storage diseases, I-cell disease/pseudo-Hurler, mucopolysaccharidoses, Sandhof/Tay-Sachs, Crigler-Najjar type II, polyendocrinopathy/hyperinsulemia, Diabetes mellitus, Laron dwarfism, myleoperoxidase deficiency, primary hypoparathyroidism, melanoma, glycanosis CDG type 1, congenital hyperthyroidism, osteogenesis imperfecta, hereditary hypofibrinogenemia, ACT deficiency, Diabetes insipidus (DI), neurophyseal DI, neprogenic DI, Charcot-Marie Tooth syndrome, Perlizaeus-Merzbacher disease, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, progressive supranuclear plasy, Pick's disease, several polyglutamine neurological disorders, Huntington's, spinocerebullar ataxia type I, spinal and bulbar muscular atrophy, dentatorubal pallidoluysian, myotonic dystrophy, spongiform encephalopathies, hereditary Creutzfeldt-Jakob disease (due to prion protein processing defect), Fabry disease, Straussler-Scheinker syndrome, COPD, dry-eye disease, Sjogren's disease, Osteoporosis, Osteopenia, Gorham's Syndrome, chloride channelopathies, myotonia congenita (Thomson and Becker forms), Bartter's syndrome type III, Dent's disease, hyperekplexia, epilepsy, hyperekplexia, lysosomal storage disease, Angelman syndrome, Primary Ciliary Dyskinesia (PCD), inherited disorders of the structure and/or function of cilia, PCD with situs inversus (also known as Kartagener syndrome), PCD without situs inversus, or ciliary aplasia.
84 . The method of claim 83 , wherein the disease is disease is cystic fibrosis, emphysema, COPD, or osteoporosis.
85 . The method of claim 83 , wherein the disease is cystic fibrosis.
86 . The method of claim 83 , wherein said patient has cystic fibrosis transmembrane receptor (CFTR) with a ΔF508 mutation, a R117H mutation, or a G551D mutation.
87 . (canceled)
88 . (canceled)
89 . The method of claim 83 , wherein the method comprises administering an additional therapeutic agent.
90 . A kit comprising a tablet, pharmaceutical composition, or dosage unit form of Compound 1, Compound 1 Form I, Compound 1 Form II, and/or Compound 1 HCl Salt Form A and instructions for use thereof.
91 . The kit of claim 90 , wherein Compound 1 is Compound 1 Form I and is present in the tablet, pharmaceutical composition, or dosage unit in an amount ranging from 25 mg to about 200 mg.
92 . The pharmaceutical composition of claim 38 , wherein the CFTR modulator is N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide.
93 . The method of claim 89 wherein the additional therapeutic agent is N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide.Join the waitlist — get patent alerts
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