IL302173A

IL302173A - Compounds and methods for the treatment of ocular disorders

Compounds and methods for the treatment of ocular disorders

Info

Publication number: IL302173A
Authority: IL; Israel
Prior art keywords: substituted; alkyl; radical; heteroalkyl; compound
Prior art date: 2020-10-21

Application number

IL302173A

Other languages

English (en)

Hebrew (he)

Original Assignee

Azura Ophthalmics Ltd

Priority date

2020-10-21

Filing date

2021-10-20

Publication date

2023-06-01

2021-10-20 Application filed by Azura Ophthalmics Ltd filed Critical Azura Ophthalmics Ltd

2023-06-01 Publication of IL302173A publication Critical patent/IL302173A/en

Links

150000001875 compounds Chemical class 0.000 title claims description 219
238000000034 method Methods 0.000 title claims description 101
238000011282 treatment Methods 0.000 title description 38
208000030533 eye disease Diseases 0.000 title description 9
125000004404 heteroalkyl group Chemical group 0.000 claims description 362
-1 within the (e.g. Chemical compound 0.000 claims description 327
125000000217 alkyl group Chemical group 0.000 claims description 287
125000001424 substituent group Chemical group 0.000 claims description 209
150000003573 thiols Chemical group 0.000 claims description 160
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 154
230000001530 keratinolytic effect Effects 0.000 claims description 148
229940124091 Keratolytic Drugs 0.000 claims description 139
CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 claims description 124
PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 claims description 120
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 120
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 103
150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 102
229910052736 halogen Inorganic materials 0.000 claims description 102
125000004043 oxo group Chemical group O=* 0.000 claims description 87
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 74
125000004001 thioalkyl group Chemical group 0.000 claims description 67
229960004308 acetylcysteine Drugs 0.000 claims description 66
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 62
PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 62
IZFHEQBZOYJLPK-SSDOTTSWSA-N (R)-dihydrolipoic acid Chemical compound OC(=O)CCCC[C@@H](S)CCS IZFHEQBZOYJLPK-SSDOTTSWSA-N 0.000 claims description 60
229960003180 glutathione Drugs 0.000 claims description 60
150000003839 salts Chemical class 0.000 claims description 57
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 55
125000000547 substituted alkyl group Chemical group 0.000 claims description 52
150000002367 halogens Chemical class 0.000 claims description 48
125000000753 cycloalkyl group Chemical group 0.000 claims description 38
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 38
235000019136 lipoic acid Nutrition 0.000 claims description 37
229960002663 thioctic acid Drugs 0.000 claims description 37
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 36
150000002148 esters Chemical class 0.000 claims description 36
230000004054 inflammatory process Effects 0.000 claims description 35
206010061218 Inflammation Diseases 0.000 claims description 34
229910052739 hydrogen Inorganic materials 0.000 claims description 34
125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 claims description 33
VUAFHZCUKUDDBC-SCSAIBSYSA-N (2s)-2-[(2-methyl-2-sulfanylpropanoyl)amino]-3-sulfanylpropanoic acid Chemical compound CC(C)(S)C(=O)N[C@H](CS)C(O)=O VUAFHZCUKUDDBC-SCSAIBSYSA-N 0.000 claims description 32
229960004272 bucillamine Drugs 0.000 claims description 32
FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 claims description 32
229960000830 captopril Drugs 0.000 claims description 32
108010024636 Glutathione Proteins 0.000 claims description 30
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 30
235000018417 cysteine Nutrition 0.000 claims description 30
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 29
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 27
150000001408 amides Chemical class 0.000 claims description 23
239000008194 pharmaceutical composition Substances 0.000 claims description 21
239000004310 lactic acid Substances 0.000 claims description 19
235000014655 lactic acid Nutrition 0.000 claims description 19
AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 19
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 19
239000012453 solvate Substances 0.000 claims description 19
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
206010020649 Hyperkeratosis Diseases 0.000 claims description 18
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 claims description 17
230000000699 topical effect Effects 0.000 claims description 16
208000022873 Ocular disease Diseases 0.000 claims description 12
230000000813 microbial effect Effects 0.000 claims description 12
108010004073 cysteinylcysteine Proteins 0.000 claims description 11
230000008595 infiltration Effects 0.000 claims description 11
238000001764 infiltration Methods 0.000 claims description 11
RHAXKFFKGZJUOE-UHFFFAOYSA-N 7-acetyl-6-ethyl-3,5,8-trihydroxy-9,10-dioxoanthracene-1,2-dicarboxylic acid Chemical compound O=C1C2=CC(O)=C(C(O)=O)C(C(O)=O)=C2C(=O)C2=C1C(O)=C(CC)C(C(C)=O)=C2O RHAXKFFKGZJUOE-UHFFFAOYSA-N 0.000 claims description 10
OABOXRPGTFRBFZ-IMJSIDKUSA-N Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-N 0.000 claims description 10
239000000546 pharmaceutical excipient Substances 0.000 claims description 10
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 9
208000001126 Keratosis Diseases 0.000 claims description 9
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical group NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 9
208000015181 infectious disease Diseases 0.000 claims description 8
230000002500 effect on skin Effects 0.000 claims description 4
150000003254 radicals Chemical class 0.000 description 374
239000000203 mixture Substances 0.000 description 125
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 71
125000005843 halogen group Chemical group 0.000 description 68
206010065062 Meibomian gland dysfunction Diseases 0.000 description 64
208000003556 Dry Eye Syndromes Diseases 0.000 description 63
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 55
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 50
239000000243 solution Substances 0.000 description 49
239000003410 keratolytic agent Substances 0.000 description 47
210000004175 meibomian gland Anatomy 0.000 description 45
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 44
125000002947 alkylene group Chemical group 0.000 description 41
210000001508 eye Anatomy 0.000 description 41
239000002904 solvent Substances 0.000 description 40
206010013774 Dry eye Diseases 0.000 description 39
125000005647 linker group Chemical group 0.000 description 38
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 37
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 34
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
208000010217 blepharitis Diseases 0.000 description 28
238000011200 topical administration Methods 0.000 description 28
125000000623 heterocyclic group Chemical group 0.000 description 27
239000012043 crude product Substances 0.000 description 25
239000007787 solid Substances 0.000 description 25
238000003786 synthesis reaction Methods 0.000 description 25
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
201000010099 disease Diseases 0.000 description 24
210000000744 eyelid Anatomy 0.000 description 24
125000001072 heteroaryl group Chemical group 0.000 description 23
125000004432 carbon atom Chemical group C* 0.000 description 22
125000004429 atom Chemical group 0.000 description 21
239000001257 hydrogen Substances 0.000 description 21
239000000126 substance Substances 0.000 description 21
FJXYZZRFMGRWLR-UHFFFAOYSA-N 2-methylpentane;propan-2-one Chemical compound CC(C)=O.CCCC(C)C FJXYZZRFMGRWLR-UHFFFAOYSA-N 0.000 description 20
208000035475 disorder Diseases 0.000 description 20
238000003818 flash chromatography Methods 0.000 description 20
210000004907 gland Anatomy 0.000 description 20
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
208000024891 symptom Diseases 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
238000009472 formulation Methods 0.000 description 19
229910052943 magnesium sulfate Inorganic materials 0.000 description 18
235000019341 magnesium sulphate Nutrition 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
229920006395 saturated elastomer Polymers 0.000 description 17
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
230000015572 biosynthetic process Effects 0.000 description 15
150000002632 lipids Chemical class 0.000 description 15
230000028327 secretion Effects 0.000 description 15
NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical compound CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 15
229960004099 azithromycin Drugs 0.000 description 14
MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 14
229910052799 carbon Inorganic materials 0.000 description 14
239000003795 chemical substances by application Substances 0.000 description 14
230000001684 chronic effect Effects 0.000 description 14
230000002757 inflammatory effect Effects 0.000 description 14
229910052757 nitrogen Inorganic materials 0.000 description 14
239000000047 product Substances 0.000 description 14
239000008186 active pharmaceutical agent Substances 0.000 description 13
125000003710 aryl alkyl group Chemical group 0.000 description 13
125000003118 aryl group Chemical group 0.000 description 13
125000004452 carbocyclyl group Chemical group 0.000 description 13
210000003491 skin Anatomy 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
235000019439 ethyl acetate Nutrition 0.000 description 12
150000002431 hydrogen Chemical class 0.000 description 12
OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 11
239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 11
230000005856 abnormality Effects 0.000 description 11
230000001154 acute effect Effects 0.000 description 11
210000004087 cornea Anatomy 0.000 description 11
125000004122 cyclic group Chemical group 0.000 description 11
125000003709 fluoroalkyl group Chemical group 0.000 description 11
125000004446 heteroarylalkyl group Chemical group 0.000 description 11
125000005842 heteroatom Chemical group 0.000 description 11
125000004415 heterocyclylalkyl group Chemical group 0.000 description 11
239000010410 layer Substances 0.000 description 11
239000003921 oil Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
239000012071 phase Substances 0.000 description 11
238000012360 testing method Methods 0.000 description 11
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
125000004450 alkenylene group Chemical group 0.000 description 10
235000019270 ammonium chloride Nutrition 0.000 description 10
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 10
235000019253 formic acid Nutrition 0.000 description 10
210000001519 tissue Anatomy 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
125000003342 alkenyl group Chemical group 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
238000002953 preparative HPLC Methods 0.000 description 9
238000005160 1H NMR spectroscopy Methods 0.000 description 8
108090000371 Esterases Proteins 0.000 description 8
239000008346 aqueous phase Substances 0.000 description 8
230000007812 deficiency Effects 0.000 description 8
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
230000000694 effects Effects 0.000 description 8
125000004474 heteroalkylene group Chemical group 0.000 description 8
230000007062 hydrolysis Effects 0.000 description 8
238000006460 hydrolysis reaction Methods 0.000 description 8
239000007924 injection Substances 0.000 description 8
238000002347 injection Methods 0.000 description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
230000007246 mechanism Effects 0.000 description 8
125000004433 nitrogen atom Chemical group N* 0.000 description 8
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
239000011550 stock solution Substances 0.000 description 8
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
239000003643 water by type Substances 0.000 description 8
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
238000003556 assay Methods 0.000 description 7
125000005884 carbocyclylalkyl group Chemical group 0.000 description 7
150000001721 carbon Chemical group 0.000 description 7
210000000695 crystalline len Anatomy 0.000 description 7
239000000463 material Substances 0.000 description 7
125000000896 monocarboxylic acid group Chemical group 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
238000002560 therapeutic procedure Methods 0.000 description 7
241000283973 Oryctolagus cuniculus Species 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
239000007983 Tris buffer Substances 0.000 description 6
GPDHNZNLPKYHCN-DZOOLQPHSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-morpholin-4-ylmethylidene]-dimethylazanium;hexafluorophosphate Chemical compound F[P-](F)(F)(F)(F)F.CCOC(=O)C(\C#N)=N/OC(=[N+](C)C)N1CCOCC1 GPDHNZNLPKYHCN-DZOOLQPHSA-N 0.000 description 6
125000005466 alkylenyl group Chemical group 0.000 description 6
208000002205 allergic conjunctivitis Diseases 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000002585 base Substances 0.000 description 6
239000000872 buffer Substances 0.000 description 6
210000000795 conjunctiva Anatomy 0.000 description 6
125000004119 disulfanediyl group Chemical group *SS* 0.000 description 6
238000012423 maintenance Methods 0.000 description 6
239000002831 pharmacologic agent Substances 0.000 description 6
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
150000003431 steroids Chemical class 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
238000010792 warming Methods 0.000 description 6
238000005406 washing Methods 0.000 description 6
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
208000009329 Graft vs Host Disease Diseases 0.000 description 5
239000007995 HEPES buffer Substances 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
208000023715 Ocular surface disease Diseases 0.000 description 5
RQBBFKINEJYDOB-UHFFFAOYSA-N acetic acid;acetonitrile Chemical compound CC#N.CC(O)=O RQBBFKINEJYDOB-UHFFFAOYSA-N 0.000 description 5
125000003545 alkoxy group Chemical group 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
206010069664 atopic keratoconjunctivitis Diseases 0.000 description 5
239000012267 brine Substances 0.000 description 5
125000004093 cyano group Chemical group *C#N 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000012530 fluid Substances 0.000 description 5
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208000024908 graft versus host disease Diseases 0.000 description 5
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230000004968 inflammatory condition Effects 0.000 description 5
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229910052760 oxygen Inorganic materials 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
229960002429 proline Drugs 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
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230000001225 therapeutic effect Effects 0.000 description 5
208000018464 vernal keratoconjunctivitis Diseases 0.000 description 5
KUUGWQVDHKXXKS-UHFFFAOYSA-N 3-acetyl-2-methyl-1,3-thiazolidine-4-carboxylic acid Chemical compound CC1SCC(C(O)=O)N1C(C)=O KUUGWQVDHKXXKS-UHFFFAOYSA-N 0.000 description 4
208000023275 Autoimmune disease Diseases 0.000 description 4
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206010010741 Conjunctivitis Diseases 0.000 description 4
201000009343 Cornelia de Lange syndrome Diseases 0.000 description 4
208000003471 De Lange Syndrome Diseases 0.000 description 4
208000009319 Keratoconjunctivitis Sicca Diseases 0.000 description 4
239000004201 L-cysteine Substances 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
208000002193 Pain Diseases 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
102000001744 Purinergic P2Y2 Receptors Human genes 0.000 description 4
108010029812 Purinergic P2Y2 Receptors Proteins 0.000 description 4
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NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 4
125000000304 alkynyl group Chemical group 0.000 description 4
230000004075 alteration Effects 0.000 description 4
239000002260 anti-inflammatory agent Substances 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
229940125773 compound 10 Drugs 0.000 description 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
210000000981 epithelium Anatomy 0.000 description 4
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 4
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238000009115 maintenance therapy Methods 0.000 description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
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SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
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239000011369 resultant mixture Substances 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
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