SK166097A3 - C-4'-modified adenosine kinase inhibitors - Google Patents

C-4'-modified adenosine kinase inhibitors Download PDF

Info

Publication number: SK166097A3
Authority: SK; Slovakia
Prior art keywords: phenyl; amino; compound; phenylamino; halogen
Prior art date: 1995-06-07

Application number

SK1660-97A

Other languages

English (en)

Slovak (sk)

Inventor

Serge H Boyer

Mark D Erion

Bheemarao G Ugarkar

Original Assignee

Metabasis Therapeutics Inc

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.)

1995-06-07

Filing date

1996-06-07

Publication date

1999-06-11

1996-06-07 Application filed by Metabasis Therapeutics Inc filed Critical Metabasis Therapeutics Inc

1999-06-11 Publication of SK166097A3 publication Critical patent/SK166097A3/sk

Links

239000003121 adenosine kinase inhibitor Substances 0.000 title abstract description 27
OOXNYFKPOPJIOT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical class Cl.Cl.C=12C(N)=NC=NC2=NC(C=2C=NC(=CC=2)N2CCOCC2)=CC=1C1=CC=CC(Br)=C1 OOXNYFKPOPJIOT-UHFFFAOYSA-N 0.000 title description 27
QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 claims abstract description 8
239000002718 pyrimidine nucleoside Substances 0.000 claims abstract description 5
-1 amino, hydroxy Chemical group 0.000 claims description 403
150000001875 compounds Chemical class 0.000 claims description 351
125000000217 alkyl group Chemical group 0.000 claims description 90
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 75
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 75
229910052739 hydrogen Inorganic materials 0.000 claims description 55
239000001257 hydrogen Substances 0.000 claims description 55
229910052736 halogen Chemical group 0.000 claims description 54
150000002367 halogens Chemical group 0.000 claims description 53
229910052757 nitrogen Chemical group 0.000 claims description 48
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 43
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 40
125000003118 aryl group Chemical group 0.000 claims description 38
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
125000003545 alkoxy group Chemical group 0.000 claims description 30
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
125000004432 carbon atom Chemical group C* 0.000 claims description 24
125000005842 heteroatom Chemical group 0.000 claims description 24
125000004430 oxygen atom Chemical group O* 0.000 claims description 23
125000005518 carboxamido group Chemical group 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
125000004093 cyano group Chemical group *C#N 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 18
125000001769 aryl amino group Chemical group 0.000 claims description 17
150000002431 hydrogen Chemical class 0.000 claims description 15
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 15
229910052760 oxygen Inorganic materials 0.000 claims description 14
239000001301 oxygen Substances 0.000 claims description 13
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
125000003282 alkyl amino group Chemical group 0.000 claims description 10
229910052799 carbon Inorganic materials 0.000 claims description 10
125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
125000003710 aryl alkyl group Chemical group 0.000 claims description 9
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
125000002252 acyl group Chemical group 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 6
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
239000011593 sulfur Chemical group 0.000 claims description 6
125000002723 alicyclic group Chemical group 0.000 claims description 5
125000004122 cyclic group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 3
125000000304 alkynyl group Chemical group 0.000 claims description 3
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
150000005676 cyclic carbonates Chemical class 0.000 claims description 3
125000001207 fluorophenyl group Chemical group 0.000 claims description 3
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
125000005110 aryl thio group Chemical group 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
125000001188 haloalkyl group Chemical group 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims 4
125000003277 amino group Chemical group 0.000 claims 2
238000002360 preparation method Methods 0.000 abstract description 111
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 abstract description 103
239000002777 nucleoside Substances 0.000 abstract description 58
239000002126 C01EB10 - Adenosine Substances 0.000 abstract description 51
229960005305 adenosine Drugs 0.000 abstract description 51
150000003833 nucleoside derivatives Chemical class 0.000 abstract description 28
230000000694 effects Effects 0.000 abstract description 22
230000004054 inflammatory process Effects 0.000 abstract description 7
238000006467 substitution reaction Methods 0.000 abstract description 7
206010061218 Inflammation Diseases 0.000 abstract description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
230000001965 increasing effect Effects 0.000 abstract description 6
235000000346 sugar Nutrition 0.000 abstract description 6
201000010099 disease Diseases 0.000 abstract description 5
150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 abstract description 4
230000002526 effect on cardiovascular system Effects 0.000 abstract description 3
208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
208000026106 cerebrovascular disease Diseases 0.000 abstract description 2
125000003843 furanosyl group Chemical group 0.000 abstract 1
230000001105 regulatory effect Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 291
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 183
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 156
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 154
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 70
239000000741 silica gel Substances 0.000 description 61
229910002027 silica gel Inorganic materials 0.000 description 61
239000000243 solution Substances 0.000 description 57
238000000034 method Methods 0.000 description 55
239000000203 mixture Substances 0.000 description 52
230000002829 reductive effect Effects 0.000 description 51
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
230000015572 biosynthetic process Effects 0.000 description 50
238000003786 synthesis reaction Methods 0.000 description 50
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 45
239000000377 silicon dioxide Substances 0.000 description 45
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
230000005764 inhibitory process Effects 0.000 description 35
239000011541 reaction mixture Substances 0.000 description 35
229920006395 saturated elastomer Polymers 0.000 description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
150000001720 carbohydrates Chemical class 0.000 description 28
108010076278 Adenosine kinase Proteins 0.000 description 27
102100032534 Adenosine kinase Human genes 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
238000003818 flash chromatography Methods 0.000 description 25
238000003756 stirring Methods 0.000 description 25
241000700159 Rattus Species 0.000 description 24
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
229910052938 sodium sulfate Inorganic materials 0.000 description 24
235000011152 sodium sulphate Nutrition 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 22
238000005859 coupling reaction Methods 0.000 description 21
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
230000008878 coupling Effects 0.000 description 20
238000010168 coupling process Methods 0.000 description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
241001465754 Metazoa Species 0.000 description 19
125000000623 heterocyclic group Chemical group 0.000 description 19
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
239000004480 active ingredient Substances 0.000 description 17
238000010511 deprotection reaction Methods 0.000 description 17
239000012044 organic layer Substances 0.000 description 17
210000002683 foot Anatomy 0.000 description 16
239000011780 sodium chloride Substances 0.000 description 16
239000003112 inhibitor Substances 0.000 description 14
206010010904 Convulsion Diseases 0.000 description 13
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 13
239000000725 suspension Substances 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
208000002193 Pain Diseases 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000002585 base Substances 0.000 description 11
238000009472 formulation Methods 0.000 description 11
239000003981 vehicle Substances 0.000 description 11
235000019270 ammonium chloride Nutrition 0.000 description 10
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 10
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
238000002474 experimental method Methods 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
239000003826 tablet Substances 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
150000001412 amines Chemical class 0.000 description 8
239000001961 anticonvulsive agent Substances 0.000 description 8
238000002347 injection Methods 0.000 description 8
239000007924 injection Substances 0.000 description 8
230000003647 oxidation Effects 0.000 description 8
238000007254 oxidation reaction Methods 0.000 description 8
239000000651 prodrug Substances 0.000 description 8
229940002612 prodrug Drugs 0.000 description 8
239000007787 solid Substances 0.000 description 8
XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 7
KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 7
WHSIXKUPQCKWBY-IOSLPCCCSA-N 5-iodotubercidin Chemical compound C1=C(I)C=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WHSIXKUPQCKWBY-IOSLPCCCSA-N 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
239000002775 capsule Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
239000000284 extract Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 7
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 6
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000001299 aldehydes Chemical class 0.000 description 6
239000000908 ammonium hydroxide Substances 0.000 description 6
230000001773 anti-convulsant effect Effects 0.000 description 6
229960003965 antiepileptics Drugs 0.000 description 6
210000003169 central nervous system Anatomy 0.000 description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
239000003814 drug Substances 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
210000000440 neutrophil Anatomy 0.000 description 6
125000003835 nucleoside group Chemical group 0.000 description 6
239000000843 powder Substances 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
239000003765 sweetening agent Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
GVSGUDGNTHCZHI-KQYNXXCUSA-N (2r,3s,4r,5r)-2-(aminomethyl)-5-(6-aminopurin-9-yl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CN)O[C@H]1N1C2=NC=NC(N)=C2N=C1 GVSGUDGNTHCZHI-KQYNXXCUSA-N 0.000 description 5
101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 5
102000055025 Adenosine deaminases Human genes 0.000 description 5
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
230000009286 beneficial effect Effects 0.000 description 5
235000014633 carbohydrates Nutrition 0.000 description 5
235000010418 carrageenan Nutrition 0.000 description 5
239000000679 carrageenan Substances 0.000 description 5
229920001525 carrageenan Polymers 0.000 description 5
229940113118 carrageenan Drugs 0.000 description 5
238000001816 cooling Methods 0.000 description 5
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 5
239000002270 dispersing agent Substances 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
235000003599 food sweetener Nutrition 0.000 description 5
239000008187 granular material Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
210000000548 hind-foot Anatomy 0.000 description 5
238000001802 infusion Methods 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000008194 pharmaceutical composition Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
230000009467 reduction Effects 0.000 description 5
230000004044 response Effects 0.000 description 5
210000002966 serum Anatomy 0.000 description 5
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 5
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 4
ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
102000003896 Myeloperoxidases Human genes 0.000 description 4
108090000235 Myeloperoxidases Proteins 0.000 description 4
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
208000006011 Stroke Diseases 0.000 description 4
229910021529 ammonia Inorganic materials 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
239000007900 aqueous suspension Substances 0.000 description 4
206010003246 arthritis Diseases 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
230000006399 behavior Effects 0.000 description 4
125000001246 bromo group Chemical group Br* 0.000 description 4
201000011510 cancer Diseases 0.000 description 4
239000007859 condensation product Substances 0.000 description 4
235000014113 dietary fatty acids Nutrition 0.000 description 4
239000000194 fatty acid Substances 0.000 description 4
229930195729 fatty acid Natural products 0.000 description 4
150000004665 fatty acids Chemical class 0.000 description 4
239000000796 flavoring agent Substances 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
238000002649 immunization Methods 0.000 description 4
230000003053 immunization Effects 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
238000001990 intravenous administration Methods 0.000 description 4
230000000302 ischemic effect Effects 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
230000026731 phosphorylation Effects 0.000 description 4
238000006366 phosphorylation reaction Methods 0.000 description 4
230000003389 potentiating effect Effects 0.000 description 4
239000003755 preservative agent Substances 0.000 description 4
230000008569 process Effects 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
210000003491 skin Anatomy 0.000 description 4
206010040882 skin lesion Diseases 0.000 description 4
231100000444 skin lesion Toxicity 0.000 description 4
239000000126 substance Substances 0.000 description 4
239000000375 suspending agent Substances 0.000 description 4
230000008961 swelling Effects 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
239000000080 wetting agent Substances 0.000 description 4
JXPDNDHCMMOJPC-UHFFFAOYSA-N 2-hydroxybutanedinitrile Chemical compound N#CC(O)CC#N JXPDNDHCMMOJPC-UHFFFAOYSA-N 0.000 description 3
QHJIWASWLMYGRR-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine;dihydrochloride Chemical compound Cl.Cl.N1=CNC2=NC=CC2=C1 QHJIWASWLMYGRR-UHFFFAOYSA-N 0.000 description 3
102000004625 Aspartate Aminotransferases Human genes 0.000 description 3
108010003415 Aspartate Aminotransferases Proteins 0.000 description 3
241000416162 Astragalus gummifer Species 0.000 description 3
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
235000010643 Leucaena leucocephala Nutrition 0.000 description 3
240000007472 Leucaena leucocephala Species 0.000 description 3
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
229920001615 Tragacanth Polymers 0.000 description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
NQGYDIOMIVPKOQ-UHFFFAOYSA-N [Li]COCC1=CC=CC=C1 Chemical compound [Li]COCC1=CC=CC=C1 NQGYDIOMIVPKOQ-UHFFFAOYSA-N 0.000 description 3
230000004913 activation Effects 0.000 description 3
239000000654 additive Substances 0.000 description 3
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 3
238000003556 assay Methods 0.000 description 3
230000008901 benefit Effects 0.000 description 3
150000005347 biaryls Chemical group 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
229910000019 calcium carbonate Inorganic materials 0.000 description 3
150000003857 carboxamides Chemical class 0.000 description 3
239000003086 colorant Substances 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
238000013270 controlled release Methods 0.000 description 3
125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
150000002009 diols Chemical class 0.000 description 3
150000004252 dithioacetals Chemical class 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000011156 evaluation Methods 0.000 description 3
239000003257 excitatory amino acid Substances 0.000 description 3
230000002461 excitatory amino acid Effects 0.000 description 3
238000001914 filtration Methods 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
230000006870 function Effects 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
150000002243 furanoses Chemical group 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
229940057995 liquid paraffin Drugs 0.000 description 3
239000002609 medium Substances 0.000 description 3
230000000926 neurological effect Effects 0.000 description 3
229940127073 nucleoside analogue Drugs 0.000 description 3
239000004006 olive oil Substances 0.000 description 3
235000008390 olive oil Nutrition 0.000 description 3
230000036961 partial effect Effects 0.000 description 3
230000010412 perfusion Effects 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
150000004944 pyrrolopyrimidines Chemical group 0.000 description 3
150000003254 radicals Chemical class 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
239000002904 solvent Substances 0.000 description 3
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
239000002562 thickening agent Substances 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
UDTIRZGWWRQEAL-KBIHSYGRSA-N (3R,4S,5R)-2-benzyl-5-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound C1(=CC=CC=C1)CC1(O)[C@H](O)[C@H](O)[C@H](O1)CO UDTIRZGWWRQEAL-KBIHSYGRSA-N 0.000 description 2
OCTYDUFUTNPBPY-YJUWBKPTSA-N (3r,4r,5r)-2-methoxy-5-(methoxymethyl)-3,4-bis(phenylmethoxy)oxolane Chemical compound O([C@H]1C(OC)O[C@@H]([C@H]1OCC=1C=CC=CC=1)COC)CC1=CC=CC=C1 OCTYDUFUTNPBPY-YJUWBKPTSA-N 0.000 description 2
ZUVKEYOGNNRSAF-FYYLOGMGSA-N (3s,4r)-1-azido-5-(1,3-dithian-2-yl)-3,4-bis(phenylmethoxy)pentan-2-one Chemical compound O([C@H](C(=O)CN=[N+]=[N-])[C@@H](CC1SCCCS1)OCC=1C=CC=CC=1)CC1=CC=CC=C1 ZUVKEYOGNNRSAF-FYYLOGMGSA-N 0.000 description 2
JMBYLDQVOMHFEQ-ISKFKSNPSA-N (3s,4r)-5-(1,3-dithian-2-yl)-1-methoxy-3,4-bis(phenylmethoxy)pentan-2-one Chemical compound O([C@H](C(=O)COC)[C@@H](CC1SCCCS1)OCC=1C=CC=CC=1)CC1=CC=CC=C1 JMBYLDQVOMHFEQ-ISKFKSNPSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
CBWBJFJMNBPWAL-UHFFFAOYSA-N 4-chloro-5-iodo-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C(I)=CN2 CBWBJFJMNBPWAL-UHFFFAOYSA-N 0.000 description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
OPNUYEGWZWHJMT-UHFFFAOYSA-N 7H-pyrrolo[2,3-d]pyrimidine trihydrochloride Chemical compound Cl.Cl.Cl.N1C=NC=C2C1=NC=C2 OPNUYEGWZWHJMT-UHFFFAOYSA-N 0.000 description 2
208000030507 AIDS Diseases 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
208000000094 Chronic Pain Diseases 0.000 description 2
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 2
YRXVCOHCIWLGFK-UHFFFAOYSA-N NC1=NC=C2C(N1)=NC=C2C1=CC=CC=C1 Chemical compound NC1=NC=C2C(N1)=NC=C2C1=CC=CC=C1 YRXVCOHCIWLGFK-UHFFFAOYSA-N 0.000 description 2
235000019483 Peanut oil Nutrition 0.000 description 2
229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
238000008050 Total Bilirubin Reagent Methods 0.000 description 2
102000003929 Transaminases Human genes 0.000 description 2
108090000340 Transaminases Proteins 0.000 description 2
LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 2
208000005298 acute pain Diseases 0.000 description 2
125000004442 acylamino group Chemical group 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
150000001336 alkenes Chemical class 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
230000002917 arthritic effect Effects 0.000 description 2
150000001543 aryl boronic acids Chemical class 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000033228 biological regulation Effects 0.000 description 2
238000001574 biopsy Methods 0.000 description 2
238000009835 boiling Methods 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
229910000389 calcium phosphate Inorganic materials 0.000 description 2
235000011010 calcium phosphates Nutrition 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical class C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
239000002131 composite material Substances 0.000 description 2
229940127204 compound 29 Drugs 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 2
230000009615 deamination Effects 0.000 description 2
238000006481 deamination reaction Methods 0.000 description 2
238000006392 deoxygenation reaction Methods 0.000 description 2
SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000012039 electrophile Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
206010015037 epilepsy Diseases 0.000 description 2
235000013305 food Nutrition 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
238000006206 glycosylation reaction Methods 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 2
229960003132 halothane Drugs 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
230000006698 induction Effects 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
239000003701 inert diluent Substances 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
238000001361 intraarterial administration Methods 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
NQMJUWWUZGVUFN-UHFFFAOYSA-N iodo(triphenoxy)phosphanium Chemical compound C=1C=CC=CC=1O[P+](OC=1C=CC=CC=1)(I)OC1=CC=CC=C1 NQMJUWWUZGVUFN-UHFFFAOYSA-N 0.000 description 2
230000003902 lesion Effects 0.000 description 2
150000007517 lewis acids Chemical class 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
210000003141 lower extremity Anatomy 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
238000006241 metabolic reaction Methods 0.000 description 2
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
238000000465 moulding Methods 0.000 description 2
229940035363 muscle relaxants Drugs 0.000 description 2
239000003158 myorelaxant agent Substances 0.000 description 2
MGNPLIACIXIYJE-UHFFFAOYSA-N n-fluoroaniline Chemical compound FNC1=CC=CC=C1 MGNPLIACIXIYJE-UHFFFAOYSA-N 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
230000004770 neurodegeneration Effects 0.000 description 2
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
239000000346 nonvolatile oil Substances 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
239000007764 o/w emulsion Substances 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
238000003305 oral gavage Methods 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
125000002524 organometallic group Chemical group 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000000312 peanut oil Substances 0.000 description 2
XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
239000006187 pill Substances 0.000 description 2
229940068918 polyethylene glycol 400 Drugs 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
230000036515 potency Effects 0.000 description 2
229940069328 povidone Drugs 0.000 description 2
239000002243 precursor Substances 0.000 description 2
230000002335 preservative effect Effects 0.000 description 2
ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
238000006798 ring closing metathesis reaction Methods 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
241000894007 species Species 0.000 description 2
210000000278 spinal cord Anatomy 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
230000001629 suppression Effects 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
235000010487 tragacanth Nutrition 0.000 description 2
239000000196 tragacanth Substances 0.000 description 2
229940116362 tragacanth Drugs 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000000844 transformation Methods 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
125000004417 unsaturated alkyl group Chemical group 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
UWNWFTYYVYWVJR-GARXJVFOSA-N (2R,3R,4S,5R)-5-(2-amino-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)-2-methyloxolane-3,4-diol Chemical compound NC=1N=CC2=C(N=1)N(C=C2C1=CC=CC=C1)[C@H]1[C@@H](O)[C@@H](O)[C@](O1)(CO)C UWNWFTYYVYWVJR-GARXJVFOSA-N 0.000 description 1
KFMNBWIVUMLJKI-JDJSBBGDSA-N (2R,3S,4R)-2-(azidomethyl)-5-methoxyoxolane-3,4-diol Chemical compound COC1O[C@H](CN=[N+]=[N-])[C@@H](O)[C@H]1O KFMNBWIVUMLJKI-JDJSBBGDSA-N 0.000 description 1
IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
XKGRTPNAKSMPGN-SDWZKWEYSA-N (2r,3r,4r)-2-(azidomethyl)-5-methoxy-3,4-bis(phenylmethoxy)oxolane Chemical compound O([C@@H]1[C@@H](CN=[N+]=[N-])OC([C@@H]1OCC=1C=CC=CC=1)OC)CC1=CC=CC=C1 XKGRTPNAKSMPGN-SDWZKWEYSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
GQHFRCCEFXYQJE-HECDAVGJSA-N (3R,4S,5R)-2-methyl-3,4,5-tris(phenylmethoxy)-5-(phenylmethoxymethyl)oxolan-2-ol Chemical compound C1(=CC=CC=C1)CO[C@]1([C@H]([C@H](C(O)(O1)C)OCC1=CC=CC=C1)OCC1=CC=CC=C1)COCC1=CC=CC=C1 GQHFRCCEFXYQJE-HECDAVGJSA-N 0.000 description 1
UDTIRZGWWRQEAL-FEZOTEKNSA-N (3S,4R,5R)-2-benzyl-5-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound C1(=CC=CC=C1)CC1(O)[C@@H](O)[C@@H](O)[C@H](O1)CO UDTIRZGWWRQEAL-FEZOTEKNSA-N 0.000 description 1
SFVQVXGNBVJNQC-YTYFACEESA-N (3r,4s)-5,5-dimethyl-3,4-bis(phenylmethoxy)oxolan-2-ol Chemical compound O([C@H]1C(O)OC([C@H]1OCC=1C=CC=CC=1)(C)C)CC1=CC=CC=C1 SFVQVXGNBVJNQC-YTYFACEESA-N 0.000 description 1
LHTPWANFYITXGL-RKEPMNIXSA-N (3r,4s,5r)-2-methoxy-5-(methoxymethyl)oxolane-3,4-diol Chemical compound COC[C@H]1OC(OC)[C@H](O)[C@@H]1O LHTPWANFYITXGL-RKEPMNIXSA-N 0.000 description 1
MYEKQLWUTBLSDY-FVOJZJPKSA-N (3r,4s,5r)-5-(azidomethyl)-5-[(4-methoxyphenyl)methoxymethyl]-3,4-bis(phenylmethoxy)oxolan-2-ol Chemical compound C1=CC(OC)=CC=C1COC[C@]1(CN=[N+]=[N-])[C@@H](OCC=2C=CC=CC=2)[C@@H](OCC=2C=CC=CC=2)C(O)O1 MYEKQLWUTBLSDY-FVOJZJPKSA-N 0.000 description 1
IHVDXAJGJGUDFX-RIFKGGETSA-N (3r,4s,5r)-5-methyl-3,4-bis(phenylmethoxy)-5-(phenylmethoxymethyl)oxolan-2-ol Chemical compound C([C@]1(C)[C@H]([C@@H](OCC=2C=CC=CC=2)C(O)O1)OCC=1C=CC=CC=1)OCC1=CC=CC=C1 IHVDXAJGJGUDFX-RIFKGGETSA-N 0.000 description 1
UZRLAIQWFNWYAN-FWYCZPIQSA-N (3r,4s,5s)-5-(1-hydroxy-2-methylprop-1-enyl)oxolane-2,3,4-triol Chemical compound CC(C)=C(O)[C@H]1OC(O)[C@H](O)[C@@H]1O UZRLAIQWFNWYAN-FWYCZPIQSA-N 0.000 description 1
ZVZCHKSCEPAUFP-PQHLKRTFSA-N (3s,4r)-5-(1,3-dithian-2-yl)-1,3,4-tris(phenylmethoxy)pentan-2-one Chemical compound O=C([C@@H](OCC=1C=CC=CC=1)[C@@H](CC1SCCCS1)OCC=1C=CC=CC=1)COCC1=CC=CC=C1 ZVZCHKSCEPAUFP-PQHLKRTFSA-N 0.000 description 1
FLTJWSFPCFZASA-PERGRGJXSA-N (3s,4r,5r)-5-(methoxymethyl)-3,4-bis(phenylmethoxy)-5-(phenylmethoxymethyl)oxolan-2-ol Chemical compound C([C@]1(COC)[C@@H]([C@H](OCC=2C=CC=CC=2)C(O)O1)OCC=1C=CC=CC=1)OCC1=CC=CC=C1 FLTJWSFPCFZASA-PERGRGJXSA-N 0.000 description 1
IHVDXAJGJGUDFX-SMVCDJAZSA-N (3s,4r,5r)-5-methyl-3,4-bis(phenylmethoxy)-5-(phenylmethoxymethyl)oxolan-2-ol Chemical compound C([C@]1(C)[C@@H]([C@H](OCC=2C=CC=CC=2)C(O)O1)OCC=1C=CC=CC=1)OCC1=CC=CC=C1 IHVDXAJGJGUDFX-SMVCDJAZSA-N 0.000 description 1
AXKGIPZJYUNAIW-UHFFFAOYSA-N (4-aminophenyl)methanol Chemical compound NC1=CC=C(CO)C=C1 AXKGIPZJYUNAIW-UHFFFAOYSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
JNVXRQOSRUDXDY-UHFFFAOYSA-N 1,1-diiodoethane Chemical compound CC(I)I JNVXRQOSRUDXDY-UHFFFAOYSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
YFVKHKCZBSGZPE-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-2-(propylamino)propan-1-one Chemical compound CCCNC(C)C(=O)C1=CC=C2OCOC2=C1 YFVKHKCZBSGZPE-UHFFFAOYSA-N 0.000 description 1
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
KSFNPHRSKZPYSG-UHFFFAOYSA-N 1-ethoxy-1,1,2-trifluoroethane Chemical compound CCOC(F)(F)CF KSFNPHRSKZPYSG-UHFFFAOYSA-N 0.000 description 1
JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 description 1
QXHDYMUPPXAMPQ-UHFFFAOYSA-N 2-(4-aminophenyl)ethanol Chemical group NC1=CC=C(CCO)C=C1 QXHDYMUPPXAMPQ-UHFFFAOYSA-N 0.000 description 1
PUBNWUYQBUCYHR-UHFFFAOYSA-N 2-(ethoxymethylidene)-4-phenylpyrrole-3-carbonitrile Chemical compound CCOC=C1N=CC(C=2C=CC=CC=2)=C1C#N PUBNWUYQBUCYHR-UHFFFAOYSA-N 0.000 description 1
FBPINGSGHKXIQA-UHFFFAOYSA-N 2-amino-3-(2-carboxyethylsulfanyl)propanoic acid Chemical compound OC(=O)C(N)CSCCC(O)=O FBPINGSGHKXIQA-UHFFFAOYSA-N 0.000 description 1
XYEJDFIDVKWWTR-UHFFFAOYSA-N 2-amino-4-phenyl-1h-pyrrole-3-carbonitrile Chemical compound N#CC1=C(N)NC=C1C1=CC=CC=C1 XYEJDFIDVKWWTR-UHFFFAOYSA-N 0.000 description 1
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical class NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
UJZWJOQRSMOFMA-UHFFFAOYSA-N 2-chloro-1-(4-fluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C=C1 UJZWJOQRSMOFMA-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
IOSAAWHGJUZBOG-UHFFFAOYSA-N 3-(6-amino-9h-purin-9-yl)nonan-2-ol Chemical compound N1=CN=C2N(C(C(C)O)CCCCCC)C=NC2=C1N IOSAAWHGJUZBOG-UHFFFAOYSA-N 0.000 description 1
HDFDQSVGZXYQOA-UHFFFAOYSA-N 4-(2-fluorophenyl)-5-phenyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound FC1=C(C=CC=C1)C1=C2C(NC(=N1)N)=NC=C2C1=CC=CC=C1 HDFDQSVGZXYQOA-UHFFFAOYSA-N 0.000 description 1
YMXQUFUYCADCFL-UHFFFAOYSA-N 4-chloro-1h-pyrazolo[3,4-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=NN2 YMXQUFUYCADCFL-UHFFFAOYSA-N 0.000 description 1
QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical group NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
FFNKBQRKZRMYCL-UHFFFAOYSA-N 5-amino-1h-pyrazole-4-carbonitrile Chemical compound NC1=NNC=C1C#N FFNKBQRKZRMYCL-UHFFFAOYSA-N 0.000 description 1
KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
USVZHTBPMMSRHY-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-chlorophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Cl USVZHTBPMMSRHY-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical group CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
102000009346 Adenosine receptors Human genes 0.000 description 1
108050000203 Adenosine receptors Proteins 0.000 description 1
102000005234 Adenosylhomocysteinase Human genes 0.000 description 1
108020002202 Adenosylhomocysteinase Proteins 0.000 description 1
241001209177 Akis Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
235000003911 Arachis Nutrition 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
206010003805 Autism Diseases 0.000 description 1
208000020706 Autistic disease Diseases 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
208000009386 Experimental Arthritis Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000796941 Homo sapiens Adenosine kinase Proteins 0.000 description 1
101001099460 Homo sapiens Myeloperoxidase Proteins 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010021118 Hypotonia Diseases 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
229930010555 Inosine Natural products 0.000 description 1
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
FFFHZYDWPBMWHY-UHFFFAOYSA-N L-Homocysteine Natural products OC(=O)C(N)CCS FFFHZYDWPBMWHY-UHFFFAOYSA-N 0.000 description 1
FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
208000008930 Low Back Pain Diseases 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
241000186359 Mycobacterium Species 0.000 description 1
UCQTVYAQUSWUBG-UHFFFAOYSA-N N,5-diphenylpyrrolo[2,3-d]pyrimidin-1-amine Chemical compound C1(=CC=CC=C1)NN1C=NC=C2C1=NC=C2C1=CC=CC=C1 UCQTVYAQUSWUBG-UHFFFAOYSA-N 0.000 description 1
KCTZOTUQSGYWLV-UHFFFAOYSA-N N1C=NC=C2N=CC=C21 Chemical compound N1C=NC=C2N=CC=C21 KCTZOTUQSGYWLV-UHFFFAOYSA-N 0.000 description 1
208000001738 Nervous System Trauma Diseases 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
206010033799 Paralysis Diseases 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
208000004983 Phantom Limb Diseases 0.000 description 1
206010056238 Phantom pain Diseases 0.000 description 1
229920005372 Plexiglas® Polymers 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
206010063837 Reperfusion injury Diseases 0.000 description 1
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
229910052772 Samarium Inorganic materials 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
206010070834 Sensitisation Diseases 0.000 description 1
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
XUFJVJSLEQLSTG-MGRQHWMJSA-N [(3r,4r)-4,5-diacetyloxyoxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1COC(OC(C)=O)[C@@H]1OC(C)=O XUFJVJSLEQLSTG-MGRQHWMJSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
238000007171 acid catalysis Methods 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004849 alkoxymethyl group Chemical group 0.000 description 1
125000005211 alkyl trimethyl ammonium group Chemical group 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001414 amino alcohols Chemical class 0.000 description 1
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
150000001448 anilines Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
230000002547 anomalous effect Effects 0.000 description 1
230000003288 anthiarrhythmic effect Effects 0.000 description 1
230000003502 anti-nociceptive effect Effects 0.000 description 1
239000003416 antiarrhythmic agent Substances 0.000 description 1
229940125681 anticonvulsant agent Drugs 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
210000002376 aorta thoracic Anatomy 0.000 description 1
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical compound N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
UGUUDTWORXNLAK-UHFFFAOYSA-N azidoalcohol Chemical compound ON=[N+]=[N-] UGUUDTWORXNLAK-UHFFFAOYSA-N 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
239000012166 beeswax Substances 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
150000003935 benzaldehydes Chemical class 0.000 description 1
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 description 1
230000008033 biological extinction Effects 0.000 description 1
230000006406 biphasic response Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000001772 blood platelet Anatomy 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
230000036770 blood supply Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
230000003925 brain function Effects 0.000 description 1
208000029028 brain injury Diseases 0.000 description 1
244000309464 bull Species 0.000 description 1
150000004657 carbamic acid derivatives Chemical group 0.000 description 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
210000004413 cardiac myocyte Anatomy 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
230000020411 cell activation Effects 0.000 description 1
230000033077 cellular process Effects 0.000 description 1
230000003727 cerebral blood flow Effects 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
230000001055 chewing effect Effects 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
230000002057 chronotropic effect Effects 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
229940126142 compound 16 Drugs 0.000 description 1
229940125807 compound 37 Drugs 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000006880 cross-coupling reaction Methods 0.000 description 1
SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 1
238000005888 cyclopropanation reaction Methods 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000005695 dehalogenation reaction Methods 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
150000004662 dithiols Chemical class 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003974 emollient agent Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
210000002889 endothelial cell Anatomy 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
230000001037 epileptic effect Effects 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
230000005284 excitation Effects 0.000 description 1
239000012467 final product Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000007306 functionalization reaction Methods 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
230000036541 health Effects 0.000 description 1
229940097789 heavy mineral oil Drugs 0.000 description 1
231100000304 hepatotoxicity Toxicity 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
210000003630 histaminocyte Anatomy 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
102000051251 human MPO Human genes 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
230000000917 hyperalgesic effect Effects 0.000 description 1
230000002631 hypothermal effect Effects 0.000 description 1
230000001146 hypoxic effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000036737 immune function Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
229940102213 injectable suspension Drugs 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229960003786 inosine Drugs 0.000 description 1
230000000297 inotrophic effect Effects 0.000 description 1
206010022437 insomnia Diseases 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
HXLVCCRPDYIRRX-UHFFFAOYSA-N iodoamine Chemical compound IN HXLVCCRPDYIRRX-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
239000002085 irritant Substances 0.000 description 1
231100000021 irritant Toxicity 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
210000004731 jugular vein Anatomy 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
238000011694 lewis rat Methods 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
230000003908 liver function Effects 0.000 description 1
230000007056 liver toxicity Effects 0.000 description 1
230000006742 locomotor activity Effects 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000007932 molded tablet Substances 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
230000004118 muscle contraction Effects 0.000 description 1
230000036640 muscle relaxation Effects 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
IRNCDKLDJPXBOD-UHFFFAOYSA-N n',n'-dimethyl-n-phenylmethanediamine Chemical compound CN(C)CNC1=CC=CC=C1 IRNCDKLDJPXBOD-UHFFFAOYSA-N 0.000 description 1
FEKWSMXKEUPBJG-UHFFFAOYSA-N n,5-diphenyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N1=CNC2=NC=C(C=3C=CC=CC=3)C2=C1NC1=CC=CC=C1 FEKWSMXKEUPBJG-UHFFFAOYSA-N 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
230000008555 neuronal activation Effects 0.000 description 1
230000008906 neuronal response Effects 0.000 description 1
201000001119 neuropathy Diseases 0.000 description 1
230000007823 neuropathy Effects 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
230000003957 neurotransmitter release Effects 0.000 description 1
210000000929 nociceptor Anatomy 0.000 description 1
108091008700 nociceptors Proteins 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
125000001979 organolithium group Chemical group 0.000 description 1
150000002905 orthoesters Chemical class 0.000 description 1
230000001151 other effect Effects 0.000 description 1
238000007248 oxidative elimination reaction Methods 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N p-hydroxybenzoic acid propyl ester Natural products CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
238000010651 palladium-catalyzed cross coupling reaction Methods 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
125000005010 perfluoroalkyl group Chemical group 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
238000006303 photolysis reaction Methods 0.000 description 1
230000015843 photosynthesis, light reaction Effects 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
230000001242 postsynaptic effect Effects 0.000 description 1
239000008057 potassium phosphate buffer Substances 0.000 description 1
FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
210000005215 presynaptic neuron Anatomy 0.000 description 1
238000002203 pretreatment Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
BXEMXLDMNMKWPV-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1 BXEMXLDMNMKWPV-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000003233 pyrroles Chemical class 0.000 description 1
150000005255 pyrrolopyridines Chemical class 0.000 description 1
238000000611 regression analysis Methods 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
230000008313 sensitization Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000003378 silver Chemical class 0.000 description 1
238000006884 silylation reaction Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
229940083466 soybean lecithin Drugs 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003509 tertiary alcohols Chemical class 0.000 description 1
YEKUWOWHPVKTCQ-UHFFFAOYSA-M tetraethylazanium;fluoride;hydrate Chemical compound O.[F-].CC[N+](CC)(CC)CC YEKUWOWHPVKTCQ-UHFFFAOYSA-M 0.000 description 1
USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000003555 thioacetals Chemical class 0.000 description 1
150000003568 thioethers Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
230000000451 tissue damage Effects 0.000 description 1
231100000827 tissue damage Toxicity 0.000 description 1
230000001256 tonic effect Effects 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
230000008733 trauma Effects 0.000 description 1
JLMIYJNXZDWSIO-UHFFFAOYSA-N triethylazanium;fluoride;hydrate Chemical compound O.[F-].CC[NH+](CC)CC JLMIYJNXZDWSIO-UHFFFAOYSA-N 0.000 description 1
POSZUTFLHGNLHX-KSBRXOFISA-N tris maleate Chemical compound OCC(N)(CO)CO.OCC(N)(CO)CO.OC(=O)\C=C/C(O)=O POSZUTFLHGNLHX-KSBRXOFISA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
150000003673 urethanes Chemical class 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000003260 vortexing Methods 0.000 description 1
239000007762 w/o emulsion Substances 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000002023 wood Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/14—Pyrrolo-pyrimidine radicals

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Pain & Pain Management (AREA)
Dermatology (AREA)
Rheumatology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Saccharide Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK1660-97A 1995-06-07 1996-06-07 C-4'-modified adenosine kinase inhibitors SK166097A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/486,161 US5674998A (en)	1989-09-15	1995-06-07	C-4' modified adenosine kinase inhibitors
PCT/US1996/010404 WO1996040705A1 (fr)	1995-06-07	1996-06-07	Inhibiteurs de l'adenosine kinase modifies en c-4'

Publications (1)

Publication Number	Publication Date
SK166097A3 true SK166097A3 (en)	1999-06-11

Family

ID=23930844

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1660-97A SK166097A3 (en)	1995-06-07	1996-06-07	C-4'-modified adenosine kinase inhibitors

Country Status (24)

Country	Link
US (1)	US5674998A (fr)
EP (1)	EP0832091B1 (fr)
JP (1)	JPH11507387A (fr)
KR (1)	KR19990022740A (fr)
CN (1)	CN1190401A (fr)
AP (1)	AP9701165A0 (fr)
AT (1)	ATE257841T1 (fr)
AU (1)	AU6178396A (fr)
BG (1)	BG102163A (fr)
BR (1)	BR9609013A (fr)
CA (1)	CA2220642A1 (fr)
CZ (1)	CZ392797A3 (fr)
DE (1)	DE69631330T2 (fr)
EA (1)	EA199800009A1 (fr)
HU (1)	HUP9802193A3 (fr)
IL (1)	IL122335A0 (fr)
IS (1)	IS4621A (fr)
MX (1)	MX9709859A (fr)
NO (1)	NO975585L (fr)
OA (1)	OA10639A (fr)
PL (1)	PL323904A1 (fr)
SK (1)	SK166097A3 (fr)
TR (1)	TR199701539T1 (fr)
WO (1)	WO1996040705A1 (fr)

Families Citing this family (76)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK0682027T3 (da) *	1994-05-03	1998-05-04	Ciba Geigy Ag	Pyrrolopyrimidinderivater med antiproliferativ virkning
DK0836605T3 (da) *	1995-07-06	2002-05-13	Novartis Ag	Pyrrolopyrimidiner og fremgangsmåder til deres fremstilling
US6051578A (en) *	1996-02-12	2000-04-18	Pfizer Inc.	Pyrazolopyrimidines for treatment of CNS disorders
US7863444B2 (en)	1997-03-19	2011-01-04	Abbott Laboratories	4-aminopyrrolopyrimidines as kinase inhibitors
US6713474B2 (en)	1998-09-18	2004-03-30	Abbott Gmbh & Co. Kg	Pyrrolopyrimidines as therapeutic agents
YU25500A (sh) *	1999-05-11	2003-08-29	Pfizer Products Inc.	Postupak za sintezu analoga nukleozida
US6831069B2 (en)	1999-08-27	2004-12-14	Ribapharm Inc.	Pyrrolo[2,3-d]pyrimidine nucleoside analogs
CA2381297A1 (fr) *	1999-08-27	2001-04-19	Esmir Gunic	Analogues nucleosidiques de pyrrolo¬2,3-d\|pyrimidine
US7071199B1 (en)	1999-09-17	2006-07-04	Abbott Gmbh & Cco. Kg	Kinase inhibitors as therapeutic agents
PT1212327E (pt)	1999-09-17	2004-01-30	Abbott Gmbh & Co Kg	Pirazolopirimidinas como agentes terapeuticos
MXPA02005959A (es) *	1999-12-16	2003-10-14	Alcon Inc	Inhibidores de adenosina cinasa para el tratamiento del nervio optico y el bano retiniano.
DE60134196D1 (de) *	2000-02-10	2008-07-10	Mitsui Chemicals Inc	Verfahren zur selektiven herstellung eines 1-phosphoryliertem zuckerderivativ-anomers und verfahren zur herstellung von nukleosiden
US7638496B2 (en)	2000-02-15	2009-12-29	Valeant Pharmaceuticals North America	Nucleoside analogs with carboxamidine modified monocyclic base
US7414036B2 (en) *	2002-01-25	2008-08-19	Muscagen Limited	Compounds useful as A3 adenosine receptor agonists
AU2002951247A0 (en) *	2002-09-06	2002-09-19	Alchemia Limited	Compounds that interact with kinases
BRPI0400869B8 (pt) *	2004-03-02	2021-05-25	Univ Estadual Campinas Unicamp	novos compostos derivados de 4-anilinoquinazolinas com propriedade inibidora de adenosinacinases
JP2008520744A (ja)	2004-11-19	2008-06-19	ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア	抗炎症性ピラゾロピリミジン
DK1848718T3 (da)	2005-02-04	2012-08-27	Millennium Pharm Inc	E1 aktiveringsenzymhæmmere
AU2006279720A1 (en) *	2005-08-12	2007-02-22	Merck & Co., Inc.	Novel 2'-C-methyl and 4'-C-methyl nucleoside derivatives
PT1989206E (pt)	2006-02-02	2012-10-15	Millennium Pharm Inc	Inibidores da enzima de ativação e1
KR20130087054A (ko)	2006-04-04	2013-08-05	더 리젠트스 오브 더 유니이버시티 오브 캘리포니아	키나제 길항물질
WO2009046448A1 (fr)	2007-10-04	2009-04-09	Intellikine, Inc.	Entités chimiques et leurs utilisations thérapeutiques
MX358640B (es) *	2008-01-04	2018-08-29	Intellikine Llc	Isoquinolin-1 (2h) -onas y tieno [2,3-d]pirimidin-4(3h) -onas substituidas, y metodos de uso de las mismas.
US8193182B2 (en) *	2008-01-04	2012-06-05	Intellikine, Inc.	Substituted isoquinolin-1(2H)-ones, and methods of use thereof
WO2009114874A2 (fr)	2008-03-14	2009-09-17	Intellikine, Inc.	Inhibiteurs de kinases (benzothiazole) et procédés d’utilisation associés
JP5547099B2 (ja)	2008-03-14	2014-07-09	インテリカイン，エルエルシー	キナーゼ阻害剤および使用方法
WO2010006072A2 (fr)	2008-07-08	2010-01-14	The Regents Of The University Of California	Modulateurs de mtor et leurs utilisations
US9096611B2 (en)	2008-07-08	2015-08-04	Intellikine Llc	Kinase inhibitors and methods of use
US8703778B2 (en)	2008-09-26	2014-04-22	Intellikine Llc	Heterocyclic kinase inhibitors
JP5819195B2 (ja)	2008-10-16	2015-11-18	ザリージェンツオブザユニバーシティオブカリフォルニア	融合環ヘテロアリールキナーゼ阻害剤
US8476431B2 (en)	2008-11-03	2013-07-02	Itellikine LLC	Benzoxazole kinase inhibitors and methods of use
JP5789252B2 (ja)	2009-05-07	2015-10-07	インテリカイン，エルエルシー	複素環式化合物およびその使用
SG175929A1 (en)	2009-05-14	2011-12-29	Millennium Pharm Inc	Hydrochloride salt of ((1s,2s,4r)-4-{4-[(1s)-2,3-dihydro-1h-inden-1-ylamino]-7h-pyrrolo [2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate
WO2011005860A2 (fr) *	2009-07-07	2011-01-13	Alnylam Pharmaceuticals, Inc.	Mimétiques de 5' phosphate
WO2011047384A2 (fr)	2009-10-16	2011-04-21	The Regents Of The University Of California	Procédés d'inhibition de l'activité ire1
EP2571357B1 (fr)	2010-05-21	2016-07-06	Infinity Pharmaceuticals, Inc.	Composés chimiques, compositions et procédés pour modulation de kinases
CN103298474B (zh)	2010-11-10	2016-06-29	无限药品股份有限公司	杂环化合物及其用途
TWI546305B (zh)	2011-01-10	2016-08-21	英菲尼提製藥股份有限公司	製備異喹啉酮之方法及異喹啉酮之固體形式
EP2678018A4 (fr)	2011-02-23	2015-09-30	Intellikine Llc	Combinaison d'inhibiteurs des kinases et utilisations associées
WO2013012918A1 (fr)	2011-07-19	2013-01-24	Infinity Pharmaceuticals Inc.	Composés hétérocycliques et leurs utilisations
AU2012284088B2 (en)	2011-07-19	2015-10-08	Infinity Pharmaceuticals Inc.	Heterocyclic compounds and uses thereof
CA2846431A1 (fr)	2011-08-29	2013-03-07	Infinity Pharmaceuticals Inc.	Composes heterocycliques et leurs utilisations
MX370814B (es)	2011-09-02	2020-01-08	Univ California	Pirazolo[3,4-d]pirimidinas sustituidas y usos de las mismas.
AU2012358803C1 (en)	2011-12-22	2019-12-19	Janssen Biopharma, Inc.	Substituted nucleosides, nucleotides and analogs thereof
US9441007B2 (en)	2012-03-21	2016-09-13	Alios Biopharma, Inc.	Substituted nucleosides, nucleotides and analogs thereof
USRE48171E1 (en)	2012-03-21	2020-08-25	Janssen Biopharma, Inc.	Substituted nucleosides, nucleotides and analogs thereof
US8940742B2 (en)	2012-04-10	2015-01-27	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
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
EP3255049A1 (fr)	2012-06-29	2017-12-13	Pfizer Inc	Nouvelles 7h-pyrrolo[2,3-d]pyrimidines substituées par un groupe amino en position 4, utilisées comme inhibiteurs de lrrk2
RU2015115631A (ru)	2012-09-26	2016-11-20	Дзе Риджентс Оф Дзе Юниверсити Оф Калифорния	Модулирование ire1
CN105102000B (zh)	2012-11-01	2021-10-22	无限药品公司	使用pi3激酶亚型调节剂的癌症疗法
US9481667B2 (en)	2013-03-15	2016-11-01	Infinity Pharmaceuticals, Inc.	Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
AU2014302715B2 (en)	2013-06-26	2018-12-06	Alios Biopharma, Inc.	Substituted nucleosides, nucleotides and analogs thereof
MX389256B (es)	2013-10-04	2025-03-20	Infinity Pharmaceuticals Inc	Compuestos heterociclicos y usos de los mismos.
US9751888B2 (en)	2013-10-04	2017-09-05	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
EP3055319A4 (fr)	2013-10-11	2018-01-10	Alios Biopharma, Inc.	Nucléosides substitués, nucléotides substitués et analogues de ceux-ci
EP3083618B1 (fr)	2013-12-17	2018-02-21	Pfizer Inc	Nouvelles 1h-pyrrolo[2,3- b]pyridines 3,4-disubstituées et 7h-pyrrolo[2,3-c]pyridazines 4,5-disubstituées en tant qu'inhibiteurs de la lrrk2
EA201691872A1 (ru)	2014-03-19	2017-04-28	Инфинити Фармасьютикалз, Инк.	Гетероциклические соединения для применения в лечении pi3k-гамма-опосредованных расстройств
WO2015160975A2 (fr)	2014-04-16	2015-10-22	Infinity Pharmaceuticals, Inc.	Polythérapies
WO2016054491A1 (fr)	2014-10-03	2016-04-07	Infinity Pharmaceuticals, Inc.	Composés hétérocycliques et leurs utilisations
EP3212201B1 (fr)	2014-10-28	2022-10-19	BCI Pharma	Inhibiteurs de la kinase nucléoside
BR112018002399A2 (pt)	2015-08-06	2018-09-25	Chimerix, Inc.	nucleosídeos de pirrolopirimidina e análogos dos mesmos, úteis como agentes antivirais
CN108349985A (zh)	2015-09-14	2018-07-31	无限药品股份有限公司	异喹啉酮的固体形式、其制备方法、包含其的组合物及其使用方法
EP3350178B1 (fr)	2015-09-14	2021-10-20	Pfizer Inc.	Nouveaux dérivés imidazo [4,5-c]quinoline et imidazo [4,5-c][1,5]naphthyridine utilisés comme inhibiteurs de lrrk2
WO2017161116A1 (fr)	2016-03-17	2017-09-21	Infinity Pharmaceuticals, Inc.	Isotopologues de composés isoquinolinone et quinazolinone et leurs utilisations comme inhibiteurs de la kinase pi3k
WO2017214269A1 (fr)	2016-06-08	2017-12-14	Infinity Pharmaceuticals, Inc.	Composés hétérocycliques et leurs utilisations
EP3474856B1 (fr)	2016-06-24	2022-09-14	Infinity Pharmaceuticals, Inc.	Therapies combinées
EP3684771B1 (fr)	2017-09-21	2024-11-27	Chimerix, Inc.	Formes morphiques de 4-amino-7-(3,4-dihydroxy-5-(hydroxyméthyle)tétrahydrofurane-2-yl)-2-méthyle-7 h-pyrrolo(2,3-d)pyrimidine-5-carboxamide et leurs utilisations
BR112022002222A2 (pt)	2019-08-08	2022-06-07	B C I Pharma	Derivados de quinolina como inibidores de proteínas quinases
US20230121698A1 (en) *	2019-12-23	2023-04-20	Sanford Burnham Prebys Medical Discovery Institute	Ectonucleotide pyrophosphatase/phosphodiesterase 1 (enpp1) modulators and uses thereof
TWI775313B (zh)	2020-02-18	2022-08-21	美商基利科學股份有限公司	抗病毒化合物
AR121356A1 (es)	2020-02-18	2022-05-11	Gilead Sciences Inc	Compuestos antivirales
TWI794742B (zh)	2020-02-18	2023-03-01	美商基利科學股份有限公司	抗病毒化合物
ES3028915T3 (en)	2021-04-16	2025-06-20	Gilead Sciences Inc	Methods of preparing carbanucleosides using amides
KR102639275B1 (ko) *	2021-06-08	2024-02-21	퓨쳐메디신 주식회사	다중 표적 인산화효소 저해 활성을 갖는 뉴클레오사이드 유도체 및 이를 포함하는 암의 예방 및 치료용 약학적 조성물
EP4387977A1 (fr)	2021-08-18	2024-06-26	Gilead Sciences, Inc.	Composés phospholipidiques et leurs procédés de production et d'utilisation

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4455420A (en) *	1983-01-13	1984-06-19	Hoffmann-La Roche Inc.	4-Amino-7-(5-deoxy-beta-D-ribofuranosyl)-5-iodo-7H-pyrrolo[2,3-d] pyrimidine
DE3712735A1 (de) *	1987-04-15	1988-11-10	Boehringer Mannheim Gmbh	Neue pyrazolo(3,4-d)pyrimidine, verfahren zu ihrer herstellung und verwendung als arzneimittel
US5506347A (en) *	1993-02-03	1996-04-09	Gensia, Inc.	Lyxofuranosyl analogues of adenosine
CA2100863A1 (fr) *	1991-01-23	1992-07-24	David A. Bullough	Inhibiteurs de l'adenosine-kinase
WO1992012718A1 (fr) *	1991-01-23	1992-08-06	Gensia, Inc.	Inhibiteurs de l'adenosine-kinase
IL108523A0 (en) *	1993-02-03	1994-05-30	Gensia Inc	Pharmaceutical compositions containing adenosine kinase inhibitors for preventing or treating conditions involving inflammatory responses and pain
US6143749A (en) *	1995-06-07	2000-11-07	Abbott Laboratories	Heterocyclic substituted cyclopentane compounds

1995
- 1995-06-07 US US08/486,161 patent/US5674998A/en not_active Expired - Fee Related
1996
- 1996-06-07 CA CA002220642A patent/CA2220642A1/fr not_active Abandoned
- 1996-06-07 CZ CZ973927A patent/CZ392797A3/cs unknown
- 1996-06-07 AU AU61783/96A patent/AU6178396A/en not_active Abandoned
- 1996-06-07 BR BR9609013-8A patent/BR9609013A/pt unknown
- 1996-06-07 CN CN96195383A patent/CN1190401A/zh active Pending
- 1996-06-07 DE DE69631330T patent/DE69631330T2/de not_active Expired - Fee Related
- 1996-06-07 AP APAP/P/1997/001165A patent/AP9701165A0/en unknown
- 1996-06-07 JP JP9502290A patent/JPH11507387A/ja not_active Ceased
- 1996-06-07 IL IL12233596A patent/IL122335A0/xx unknown
- 1996-06-07 KR KR1019970709182A patent/KR19990022740A/ko not_active Withdrawn
- 1996-06-07 EP EP96919442A patent/EP0832091B1/fr not_active Expired - Lifetime
- 1996-06-07 TR TR97/01539T patent/TR199701539T1/xx unknown
- 1996-06-07 HU HU9802193A patent/HUP9802193A3/hu unknown
- 1996-06-07 PL PL96323904A patent/PL323904A1/xx unknown
- 1996-06-07 EA EA199800009A patent/EA199800009A1/ru unknown
- 1996-06-07 SK SK1660-97A patent/SK166097A3/sk unknown
- 1996-06-07 WO PCT/US1996/010404 patent/WO1996040705A1/fr not_active Ceased
- 1996-06-07 AT AT96919442T patent/ATE257841T1/de not_active IP Right Cessation
1997
- 1997-11-26 IS IS4621A patent/IS4621A/is unknown
- 1997-12-03 NO NO975585A patent/NO975585L/no unknown
- 1997-12-03 OA OA70150A patent/OA10639A/en unknown
- 1997-12-08 MX MX9709859A patent/MX9709859A/es unknown
1998
- 1998-01-07 BG BG102163A patent/BG102163A/xx unknown

Also Published As

Publication number	Publication date
JPH11507387A (ja)	1999-06-29
DE69631330T2 (de)	2004-10-28
HUP9802193A2 (hu)	1999-05-28
AU6178396A (en)	1996-12-30
NO975585D0 (no)	1997-12-03
CN1190401A (zh)	1998-08-12
WO1996040705A1 (fr)	1996-12-19
DE69631330D1 (de)	2004-02-19
OA10639A (en)	2002-09-17
KR19990022740A (ko)	1999-03-25
CA2220642A1 (fr)	1996-12-19
EA199800009A1 (ru)	1998-06-25
PL323904A1 (en)	1998-04-27
EP0832091B1 (fr)	2004-01-14
CZ392797A3 (cs)	1999-04-14
TR199701539T1 (xx)	1998-04-21
HUP9802193A3 (en)	1999-10-28
EP0832091A1 (fr)	1998-04-01
MX9709859A (es)	1998-08-30
NO975585L (no)	1998-02-05
IS4621A (is)	1997-11-26
US5674998A (en)	1997-10-07
ATE257841T1 (de)	2004-01-15
AP9701165A0 (en)	1998-01-31
BG102163A (en)	1998-10-30
BR9609013A (pt)	1999-12-14
IL122335A0 (en)	1998-04-05

Publication	Publication Date	Title
SK166097A3 (en)	1999-06-11	C-4'-modified adenosine kinase inhibitors
US5763596A (en)	1998-06-09	C-4' modified adenosine kinase inhibitors
US5763597A (en)	1998-06-09	Orally active adenosine kinase inhibitors
US5721356A (en)	1998-02-24	Orally active adenosine kinase inhibitors
US5795977A (en)	1998-08-18	Water soluble adenosine kinase inhibitors
US5726302A (en)	1998-03-10	Water soluble adenosine kinase inhibitors
DE69230347T2 (de)	2000-07-06	Adenosinkinaseinhibitoren
JPH08506343A (ja)	1996-07-09	リキソフラノシル誘導体を含むアデノシンキナーゼ阻害物質
DE3924424A1 (de)	1991-01-31	Nucleosid-derivate, verfahren zu deren herstellung, deren verwendung als arzneimittel sowie deren verwendung bei der nucleinsaeure-sequenzierung
US5777100A (en)	1998-07-07	AICA riboside analogs
JP2009102366A (ja)	2009-05-14	Ａｉｃａリボシド類縁体
MXPA97009656A (en)	1999-01-11	Soluble adenosin kinase inhibitors in a
MXPA97009773A (en)	1999-01-11	Inhibitors of adenosin cinasa oralmente acti
IE920190A1 (en)	1992-07-29	Adenosine kinase inhibitors