CA2555724A1

CA2555724A1 - 2-(pyridin-3-ylamino)-pyrido[2,3-d]pyrimidin-7-ones

2-(pyridin-3-ylamino)-pyrido[2,3-d]pyrimidin-7-ones Download PDF

Info

Publication number: CA2555724A1
Authority: CA; Canada
Prior art keywords: pyrido; ylamino; pyridin; pyrimidin; piperazin
Prior art date: 2004-02-18
Legal status : Abandoned

Application number

CA002555724A

Other languages

English (en)

French (fr)

Inventor

Mark Robert Barvian

Peter Laurence Toogood

Scott Norman Vanderwel

Current Assignee

Warner Lambert Co LLC

Original Assignee

Individual

Priority date

2004-02-18

Filing date

2005-02-07

Publication date

2005-09-09

2005-02-07 Application filed by Individual filed Critical Individual

2005-09-09 Publication of CA2555724A1 publication Critical patent/CA2555724A1/en

Status Abandoned legal-status Critical Current

Links

BXOSYWAUOOEKIH-UHFFFAOYSA-N 2-(pyridin-3-ylamino)-6h-pyrido[2,3-d]pyrimidin-7-one Chemical class N=1C2=NC(=O)CC=C2C=NC=1NC1=CC=CN=C1 BXOSYWAUOOEKIH-UHFFFAOYSA-N 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims abstract description 113
-1 N-hydroxyacetamido Chemical group 0.000 claims description 64
150000003839 salts Chemical class 0.000 claims description 49
238000000034 method Methods 0.000 claims description 32
125000000217 alkyl group Chemical group 0.000 claims description 30
229910052739 hydrogen Inorganic materials 0.000 claims description 29
239000001257 hydrogen Substances 0.000 claims description 29
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
150000002431 hydrogen Chemical group 0.000 claims description 22
229910052757 nitrogen Inorganic materials 0.000 claims description 22
125000003118 aryl group Chemical group 0.000 claims description 21
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
125000001072 heteroaryl group Chemical group 0.000 claims description 20
206010028980 Neoplasm Diseases 0.000 claims description 17
125000000753 cycloalkyl group Chemical group 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 16
150000002367 halogens Chemical group 0.000 claims description 15
125000000623 heterocyclic group Chemical group 0.000 claims description 15
208000035475 disorder Diseases 0.000 claims description 14
201000011510 cancer Diseases 0.000 claims description 13
150000002148 esters Chemical class 0.000 claims description 12
150000001408 amides Chemical class 0.000 claims description 11
229910020008 S(O) Inorganic materials 0.000 claims description 10
125000003710 aryl alkyl group Chemical group 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
239000000651 prodrug Substances 0.000 claims description 10
229940002612 prodrug Drugs 0.000 claims description 10
230000004663 cell proliferation Effects 0.000 claims description 9
125000005842 heteroatom Chemical group 0.000 claims description 9
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
125000004430 oxygen atom Chemical group O* 0.000 claims description 6
210000003800 pharynx Anatomy 0.000 claims description 6
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
230000002159 abnormal effect Effects 0.000 claims description 5
208000009956 adenocarcinoma Diseases 0.000 claims description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
230000035755 proliferation Effects 0.000 claims description 5
208000037803 restenosis Diseases 0.000 claims description 5
239000011593 sulfur Chemical group 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
NXIFVKBQTCUXOE-UHFFFAOYSA-N 6-bromo-8-cyclopentyl-5-methyl-2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(NC=3C=NC(=CC=3)N3CCOCC3)=NC=C2C(C)=C(Br)C(=O)N1C1CCCC1 NXIFVKBQTCUXOE-UHFFFAOYSA-N 0.000 claims description 4
TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims description 4
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
210000000214 mouth Anatomy 0.000 claims description 4
210000002464 muscle smooth vascular Anatomy 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
210000003491 skin Anatomy 0.000 claims description 4
RXUXPYCEJKWINO-UHFFFAOYSA-N 6-acetyl-8-cyclopentyl-5-methyl-2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=C(C)C2=CN=C1NC(C=N1)=CC=C1N1CCOCC1 RXUXPYCEJKWINO-UHFFFAOYSA-N 0.000 claims description 3
WMEIBDGEPLSTOW-UHFFFAOYSA-N 6-bromo-8-cyclopentyl-5-methyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(NC=3C=NC(=CC=3)N3CCNCC3)=NC=C2C(C)=C(Br)C(=O)N1C1CCCC1 WMEIBDGEPLSTOW-UHFFFAOYSA-N 0.000 claims description 3
208000003200 Adenoma Diseases 0.000 claims description 3
206010001233 Adenoma benign Diseases 0.000 claims description 3
201000001320 Atherosclerosis Diseases 0.000 claims description 3
206010005003 Bladder cancer Diseases 0.000 claims description 3
201000009030 Carcinoma Diseases 0.000 claims description 3
208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 claims description 3
206010073069 Hepatic cancer Diseases 0.000 claims description 3
208000017604 Hodgkin disease Diseases 0.000 claims description 3
206010023347 Keratoacanthoma Diseases 0.000 claims description 3
206010029260 Neuroblastoma Diseases 0.000 claims description 3
206010038389 Renal cancer Diseases 0.000 claims description 3
206010039491 Sarcoma Diseases 0.000 claims description 3
201000010208 Seminoma Diseases 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 3
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
125000004103 aminoalkyl group Chemical group 0.000 claims description 3
201000001531 bladder carcinoma Diseases 0.000 claims description 3
210000000988 bone and bone Anatomy 0.000 claims description 3
210000000133 brain stem Anatomy 0.000 claims description 3
150000001721 carbon Chemical group 0.000 claims description 3
125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
210000003169 central nervous system Anatomy 0.000 claims description 3
210000003679 cervix uteri Anatomy 0.000 claims description 3
210000001072 colon Anatomy 0.000 claims description 3
125000004663 dialkyl amino group Chemical group 0.000 claims description 3
210000003238 esophagus Anatomy 0.000 claims description 3
208000005017 glioblastoma Diseases 0.000 claims description 3
206010073071 hepatocellular carcinoma Diseases 0.000 claims description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
208000003849 large cell carcinoma Diseases 0.000 claims description 3
210000002429 large intestine Anatomy 0.000 claims description 3
208000032839 leukemia Diseases 0.000 claims description 3
210000000088 lip Anatomy 0.000 claims description 3
201000002250 liver carcinoma Diseases 0.000 claims description 3
210000004072 lung Anatomy 0.000 claims description 3
201000001441 melanoma Diseases 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
210000001672 ovary Anatomy 0.000 claims description 3
210000000496 pancreas Anatomy 0.000 claims description 3
201000010198 papillary carcinoma Diseases 0.000 claims description 3
210000002307 prostate Anatomy 0.000 claims description 3
210000000664 rectum Anatomy 0.000 claims description 3
201000010174 renal carcinoma Diseases 0.000 claims description 3
210000000813 small intestine Anatomy 0.000 claims description 3
206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
210000002784 stomach Anatomy 0.000 claims description 3
210000001550 testis Anatomy 0.000 claims description 3
210000001685 thyroid gland Anatomy 0.000 claims description 3
208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims description 3
210000002105 tongue Anatomy 0.000 claims description 3
208000010576 undifferentiated carcinoma Diseases 0.000 claims description 3
208000010570 urinary bladder carcinoma Diseases 0.000 claims description 3
XRTACFOJSFSFIW-UHFFFAOYSA-N 2-[(6-piperazin-1-ylpyridin-3-yl)amino]-8-propan-2-yl-6-(1,3-thiazol-2-yl)pyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C=C(C=3SC=CN=3)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CCNCC1 XRTACFOJSFSFIW-UHFFFAOYSA-N 0.000 claims description 2
GHYUVIGBANFJNG-UHFFFAOYSA-N 2-[[6-(3,5-dimethylpiperazin-1-yl)pyridin-3-yl]amino]-6-(hydroxymethyl)-5-methyl-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C(C)=C(CO)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CC(C)NC(C)C1 GHYUVIGBANFJNG-UHFFFAOYSA-N 0.000 claims description 2
JZJNGDAXALEGQI-UHFFFAOYSA-N 2-[[6-(3,5-dimethylpiperazin-1-yl)pyridin-3-yl]amino]-6-(hydroxymethyl)-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C=C(CO)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CC(C)NC(C)C1 JZJNGDAXALEGQI-UHFFFAOYSA-N 0.000 claims description 2
ZKWJVCJSTZSQSL-UHFFFAOYSA-N 2-[[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino]-6-phenoxy-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C=C(OC=3C=CC=CC=3)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CCN(C)CC1 ZKWJVCJSTZSQSL-UHFFFAOYSA-N 0.000 claims description 2
ICEMITYCGODOAD-UHFFFAOYSA-N 3-[6-fluoro-5-methyl-7-oxo-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-8-yl]propanoic acid Chemical compound N=1C=C2C(C)=C(F)C(=O)N(CCC(O)=O)C2=NC=1NC(C=N1)=CC=C1N1CCNCC1 ICEMITYCGODOAD-UHFFFAOYSA-N 0.000 claims description 2
WXWVSYQRYRNFBY-UHFFFAOYSA-N 3-[6-fluoro-7-oxo-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-8-yl]propanoic acid Chemical compound N=1C=C2C=C(F)C(=O)N(CCC(=O)O)C2=NC=1NC(C=N1)=CC=C1N1CCNCC1 WXWVSYQRYRNFBY-UHFFFAOYSA-N 0.000 claims description 2
SYSCRMLHWJBHMQ-UHFFFAOYSA-N 5-methyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]-8-propan-2-yl-6-(1,3-thiazol-2-yl)pyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C(C)=C(C=3SC=CN=3)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CCNCC1 SYSCRMLHWJBHMQ-UHFFFAOYSA-N 0.000 claims description 2
MXCBDHVXPSUVIZ-UHFFFAOYSA-N 5-methyl-2-[[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino]-6-phenoxy-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C(C)=C(OC=3C=CC=CC=3)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CCN(C)CC1 MXCBDHVXPSUVIZ-UHFFFAOYSA-N 0.000 claims description 2
GYSUUFRNQZYUNG-UHFFFAOYSA-N 6-acetyl-2-[(5-chloro-6-piperazin-1-ylpyridin-3-yl)amino]-5-methyl-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C(C)=C(C(C)=O)C(=O)N(C(C)C)C2=NC=1NC(C=C1Cl)=CN=C1N1CCNCC1 GYSUUFRNQZYUNG-UHFFFAOYSA-N 0.000 claims description 2
ACFOEHLOSQTBFN-UHFFFAOYSA-N 6-acetyl-2-[(5-chloro-6-piperazin-1-ylpyridin-3-yl)amino]-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C=C(C(C)=O)C(=O)N(C(C)C)C2=NC=1NC(C=C1Cl)=CN=C1N1CCNCC1 ACFOEHLOSQTBFN-UHFFFAOYSA-N 0.000 claims description 2
LKCSZNHDJJQUDO-UHFFFAOYSA-N 6-acetyl-5-methyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C(C)=C(C(C)=O)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CCNCC1 LKCSZNHDJJQUDO-UHFFFAOYSA-N 0.000 claims description 2
DJJBZVAMSAAMPS-UHFFFAOYSA-N 6-acetyl-8-cyclopentyl-2-[[6-(1,4-diazepan-1-yl)pyridin-3-yl]amino]-5-methylpyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=C(C)C2=CN=C1NC(C=N1)=CC=C1N1CCCNCC1 DJJBZVAMSAAMPS-UHFFFAOYSA-N 0.000 claims description 2
SZHNTQBSCCDDTP-UHFFFAOYSA-N 6-acetyl-8-cyclopentyl-2-[[6-(1,4-diazepan-1-yl)pyridin-3-yl]amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=CC2=CN=C1NC(C=N1)=CC=C1N1CCCNCC1 SZHNTQBSCCDDTP-UHFFFAOYSA-N 0.000 claims description 2
PSRAOXPOEYRNJN-UHFFFAOYSA-N 6-acetyl-8-cyclopentyl-5-methyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=C(C)C2=CN=C1NC(C=N1)=CC=C1N1CCNCC1 PSRAOXPOEYRNJN-UHFFFAOYSA-N 0.000 claims description 2
ZXJGRNNMEMXMHV-UHFFFAOYSA-N 6-anilino-8-(2-cyclopropylethyl)-5-methyl-2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1N(CCC2CC2)C2=NC(NC=3C=NC(=CC=3)N3CCOCC3)=NC=C2C(C)=C1NC1=CC=CC=C1 ZXJGRNNMEMXMHV-UHFFFAOYSA-N 0.000 claims description 2
ZZCWERBNMNIVBT-UHFFFAOYSA-N 6-benzyl-2-[[6-(2-methoxyethoxy)pyridin-3-yl]amino]-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound C1=NC(OCCOC)=CC=C1NC1=NC=C(C=C(CC=2C=CC=CC=2)C(=O)N2C(C)C)C2=N1 ZZCWERBNMNIVBT-UHFFFAOYSA-N 0.000 claims description 2
COAONMXILAOQEL-UHFFFAOYSA-N 6-bromo-8-cyclopentyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(Br)=CC2=CN=C1NC(C=N1)=CC=C1N1CCNCC1 COAONMXILAOQEL-UHFFFAOYSA-N 0.000 claims description 2
RZGWHKQRFXPQCW-UHFFFAOYSA-N 6-chloro-5-methyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C(C)=C(Cl)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CCNCC1 RZGWHKQRFXPQCW-UHFFFAOYSA-N 0.000 claims description 2
OUIYDOZEILYEER-UHFFFAOYSA-N 6-ethyl-8-(2-methoxyethyl)-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(CCOC)C(=O)C(CC)=CC2=CN=C1NC(C=N1)=CC=C1N1CCNCC1 OUIYDOZEILYEER-UHFFFAOYSA-N 0.000 claims description 2
INSFBQSSSGSXHU-UHFFFAOYSA-N 8-benzyl-6-ethenyl-5-methyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(NC=3C=NC(=CC=3)N3CCNCC3)=NC=C2C(C)=C(C=C)C(=O)N1CC1=CC=CC=C1 INSFBQSSSGSXHU-UHFFFAOYSA-N 0.000 claims description 2
PYINCEJKNQPDTH-UHFFFAOYSA-N 8-cyclopentyl-2-[(6-methoxypyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound C1=NC(OC)=CC=C1NC1=NC=C(C=CC(=O)N2C3CCCC3)C2=N1 PYINCEJKNQPDTH-UHFFFAOYSA-N 0.000 claims description 2
JGFMSHIAADSSQQ-UHFFFAOYSA-N 8-cyclopentyl-2-[(6-piperidin-1-ylpyridin-3-yl)amino]-6-propanoylpyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)CC)=CC2=CN=C1NC(C=N1)=CC=C1N1CCCCC1 JGFMSHIAADSSQQ-UHFFFAOYSA-N 0.000 claims description 2
OCWBBHMCBIZQKB-UHFFFAOYSA-N 8-cyclopentyl-5-methyl-2-[(6-piperidin-1-ylpyridin-3-yl)amino]-6-propanoylpyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)CC)=C(C)C2=CN=C1NC(C=N1)=CC=C1N1CCCCC1 OCWBBHMCBIZQKB-UHFFFAOYSA-N 0.000 claims description 2
UUHHKLZMMAJVJK-UHFFFAOYSA-N 8-cyclopentyl-6-ethyl-5-methyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(C3CCCC3)C(=O)C(CC)=C(C)C2=CN=C1NC(C=N1)=CC=C1N1CCNCC1 UUHHKLZMMAJVJK-UHFFFAOYSA-N 0.000 claims description 2
HODVWRBGNQTDGL-UHFFFAOYSA-N 8-propan-2-yl-2-(pyridin-3-ylamino)pyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C=CC(=O)N(C(C)C)C2=NC=1NC1=CC=CN=C1 HODVWRBGNQTDGL-UHFFFAOYSA-N 0.000 claims description 2
201000009273 Endometriosis Diseases 0.000 claims description 2
206010057469 Vascular stenosis Diseases 0.000 claims description 2
OBZPDIYUEBSWTH-UHFFFAOYSA-N ethyl 5-methyl-7-oxo-2-[(6-piperazin-1-ylpyridin-3-yl)amino]-8-propan-2-ylpyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=C2N(C(C)C)C(=O)C(C(=O)OCC)=C(C)C2=CN=C1NC(C=N1)=CC=C1N1CCNCC1 OBZPDIYUEBSWTH-UHFFFAOYSA-N 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 7
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims 1
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
IZWKSYQYHZKCBL-UHFFFAOYSA-N 6-anilino-8-(2-cyclopropylethyl)-2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound C=1C2=CN=C(NC=3C=NC(=CC=3)N3CCOCC3)N=C2N(CCC2CC2)C(=O)C=1NC1=CC=CC=C1 IZWKSYQYHZKCBL-UHFFFAOYSA-N 0.000 claims 1
YITJUFUSEPCUJX-UHFFFAOYSA-N 6-ethyl-8-(2-methoxyethyl)-5-methyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(CCOC)C(=O)C(CC)=C(C)C2=CN=C1NC(C=N1)=CC=C1N1CCNCC1 YITJUFUSEPCUJX-UHFFFAOYSA-N 0.000 claims 1
WMOJNXOQMYZLIB-UHFFFAOYSA-N 6-ethynyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C=C(C#C)C(=O)N(C(C)C)C2=NC=1NC(C=N1)=CC=C1N1CCNCC1 WMOJNXOQMYZLIB-UHFFFAOYSA-N 0.000 claims 1
JWYCJOFYBBZCCR-UHFFFAOYSA-N 8-[2-(dimethylamino)ethyl]-6-ethynyl-5-methyl-2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C(C)=C(C#C)C(=O)N(CCN(C)C)C2=NC=1NC(C=N1)=CC=C1N1CCOCC1 JWYCJOFYBBZCCR-UHFFFAOYSA-N 0.000 claims 1
KBLKSMPPZYUQAB-UHFFFAOYSA-N 8-benzyl-6-ethenyl-2-[(6-piperazin-1-ylpyridin-3-yl)amino]pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=C2N(CC=3C=CC=CC=3)C(=O)C(C=C)=CC2=CN=C1NC(C=N1)=CC=C1N1CCNCC1 KBLKSMPPZYUQAB-UHFFFAOYSA-N 0.000 claims 1
208000026310 Breast neoplasm Diseases 0.000 claims 1
101100134922 Gallus gallus COR5 gene Proteins 0.000 claims 1
108091008648 NR7C Proteins 0.000 claims 1
JOLGSHXGVFCISU-UHFFFAOYSA-N ethyl 7-oxo-2-[(6-piperazin-1-ylpyridin-3-yl)amino]-8-propan-2-ylpyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=C2N(C(C)C)C(=O)C(C(=O)OCC)=CC2=CN=C1NC(C=N1)=CC=C1N1CCNCC1 JOLGSHXGVFCISU-UHFFFAOYSA-N 0.000 claims 1
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
150000002825 nitriles Chemical class 0.000 claims 1
108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 abstract description 12
102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 abstract description 11
101150073031 cdk2 gene Proteins 0.000 abstract description 11
102000003903 Cyclin-dependent kinases Human genes 0.000 abstract description 9
108090000266 Cyclin-dependent kinases Proteins 0.000 abstract description 9
108091007914 CDKs Proteins 0.000 abstract description 6
230000002062 proliferating effect Effects 0.000 abstract description 6
239000003112 inhibitor Substances 0.000 abstract description 3
239000000203 mixture Substances 0.000 description 50
238000009472 formulation Methods 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 19
230000000694 effects Effects 0.000 description 19
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
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 16
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 16
239000002253 acid Substances 0.000 description 16
239000002585 base Substances 0.000 description 15
239000000872 buffer Substances 0.000 description 15
238000002360 preparation method Methods 0.000 description 15
239000000243 solution Substances 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
239000000843 powder Substances 0.000 description 13
239000007787 solid Substances 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
125000003545 alkoxy group Chemical group 0.000 description 12
230000005764 inhibitory process Effects 0.000 description 12
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 12
239000003826 tablet Substances 0.000 description 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
125000003342 alkenyl group Chemical group 0.000 description 10
125000000304 alkynyl group Chemical group 0.000 description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000012360 testing method Methods 0.000 description 9
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
239000002775 capsule Substances 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 8
201000010099 disease Diseases 0.000 description 8
239000012458 free base Substances 0.000 description 8
239000007788 liquid Substances 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
125000001424 substituent group Chemical group 0.000 description 8
102000004190 Enzymes Human genes 0.000 description 7
108090000790 Enzymes Proteins 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
239000002552 dosage form Substances 0.000 description 7
235000019441 ethanol Nutrition 0.000 description 7
125000005843 halogen group Chemical group 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
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 6
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
238000003556 assay Methods 0.000 description 6
239000000969 carrier Substances 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000003814 drug Substances 0.000 description 6
239000008101 lactose Substances 0.000 description 6
239000008194 pharmaceutical composition Substances 0.000 description 6
235000013772 propylene glycol Nutrition 0.000 description 6
239000000725 suspension Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
108091008794 FGF receptors Proteins 0.000 description 5
102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
125000002252 acyl group Chemical group 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
229940079593 drug Drugs 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
229920000642 polymer Polymers 0.000 description 5
239000000758 substrate Substances 0.000 description 5
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 4
229920000858 Cyclodextrin Polymers 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
102000001253 Protein Kinase Human genes 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
229910052784 alkaline earth metal Inorganic materials 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
229940099112 cornstarch Drugs 0.000 description 4
239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 4
238000006073 displacement reaction Methods 0.000 description 4
239000000796 flavoring agent Substances 0.000 description 4
229910052731 fluorine Inorganic materials 0.000 description 4
125000004356 hydroxy functional group Chemical group O* 0.000 description 4
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
238000011534 incubation Methods 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
239000003446 ligand Substances 0.000 description 4
239000007937 lozenge Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
229920000609 methyl cellulose Polymers 0.000 description 4
235000010981 methylcellulose Nutrition 0.000 description 4
239000001923 methylcellulose Substances 0.000 description 4
150000007522 mineralic acids Chemical class 0.000 description 4
150000002829 nitrogen Chemical class 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
108060006633 protein kinase Proteins 0.000 description 4
150000003222 pyridines Chemical class 0.000 description 4
230000000717 retained effect Effects 0.000 description 4
239000007921 spray Substances 0.000 description 4
150000003457 sulfones Chemical class 0.000 description 4
150000003462 sulfoxides Chemical class 0.000 description 4
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
229910014585 C2-Ce Inorganic materials 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
239000004215 Carbon black (E152) Substances 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
102000016736 Cyclin Human genes 0.000 description 3
108050006400 Cyclin Proteins 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
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 3
239000007864 aqueous solution Substances 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
239000008280 blood Substances 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
229940110456 cocoa butter Drugs 0.000 description 3
235000019868 cocoa butter Nutrition 0.000 description 3
229940127089 cytotoxic agent Drugs 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
229960001484 edetic acid Drugs 0.000 description 3
238000001952 enzyme assay Methods 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
235000019634 flavors Nutrition 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
239000006260 foam Substances 0.000 description 3
239000000499 gel Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
229940014259 gelatin Drugs 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
238000010348 incorporation Methods 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000007924 injection Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000012669 liquid formulation Substances 0.000 description 3
229910001629 magnesium chloride Inorganic materials 0.000 description 3
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
206010039073 rheumatoid arthritis Diseases 0.000 description 3
150000003335 secondary amines Chemical class 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
229940032147 starch Drugs 0.000 description 3
239000000829 suppository Substances 0.000 description 3
239000007916 tablet composition Substances 0.000 description 3
239000001993 wax Substances 0.000 description 3
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
208000023275 Autoimmune disease Diseases 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
102000002554 Cyclin A Human genes 0.000 description 2
108010068192 Cyclin A Proteins 0.000 description 2
102000003910 Cyclin D Human genes 0.000 description 2
108090000259 Cyclin D Proteins 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
241000450599 DNA viruses Species 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
206010018364 Glomerulonephritis Diseases 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
229910021380 Manganese Chloride Inorganic materials 0.000 description 2
GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
108091000080 Phosphotransferase Proteins 0.000 description 2
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
108050002653 Retinoblastoma protein Proteins 0.000 description 2
229940124639 Selective inhibitor Drugs 0.000 description 2
241000700584 Simplexvirus Species 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
239000003513 alkali Substances 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
230000008485 antagonism Effects 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
150000007514 bases Chemical class 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
210000000481 breast Anatomy 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
231100000357 carcinogen Toxicity 0.000 description 2
239000003183 carcinogenic agent Substances 0.000 description 2
238000006555 catalytic reaction Methods 0.000 description 2
230000006369 cell cycle progression Effects 0.000 description 2
229940124444 chemoprotective agent Drugs 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
241001493065 dsRNA viruses Species 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
210000002950 fibroblast Anatomy 0.000 description 2
239000012530 fluid Substances 0.000 description 2
230000006870 function Effects 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
239000008187 granular material Substances 0.000 description 2
238000005469 granulation Methods 0.000 description 2
230000003179 granulation Effects 0.000 description 2
230000009036 growth inhibition Effects 0.000 description 2
125000001188 haloalkyl group Chemical group 0.000 description 2
206010020718 hyperplasia Diseases 0.000 description 2
239000007943 implant Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
238000010902 jet-milling Methods 0.000 description 2
239000002502 liposome Substances 0.000 description 2
206010025135 lupus erythematosus Diseases 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000011565 manganese chloride Substances 0.000 description 2
235000002867 manganese chloride Nutrition 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
238000013508 migration Methods 0.000 description 2
239000003595 mist Substances 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
239000002674 ointment Substances 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
230000003204 osmotic effect Effects 0.000 description 2
125000001715 oxadiazolyl group Chemical group 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
239000002245 particle Substances 0.000 description 2
235000019271 petrolatum Nutrition 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
229910000073 phosphorus hydride Inorganic materials 0.000 description 2
102000020233 phosphotransferase Human genes 0.000 description 2
230000000704 physical effect Effects 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000008569 process Effects 0.000 description 2
238000012545 processing Methods 0.000 description 2
239000003380 propellant Substances 0.000 description 2
BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical group C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 2
230000009467 reduction Effects 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 2
229940048086 sodium pyrophosphate Drugs 0.000 description 2
239000012453 solvate Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
125000000547 substituted alkyl group Chemical group 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
210000005222 synovial tissue Anatomy 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
IUNODSXHWLAMDU-UHFFFAOYSA-N tert-butyl 4-[5-[(6-bromo-8-cyclopentyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(N=C1)=CC=C1NC1=NC=C(C=C(Br)C(=O)N2C3CCCC3)C2=N1 IUNODSXHWLAMDU-UHFFFAOYSA-N 0.000 description 2
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
235000019818 tetrasodium diphosphate Nutrition 0.000 description 2
239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
239000002562 thickening agent Substances 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
235000012431 wafers Nutrition 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
DOTAAODFKPTVCK-UHFFFAOYSA-N (1-diphenylphosphanyl-9h-xanthen-2-yl)-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C1=C2CC3=CC=CC=C3OC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 DOTAAODFKPTVCK-UHFFFAOYSA-N 0.000 description 1
KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-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
KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical group CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
MHHOMHMNIRXARC-UHFFFAOYSA-N 1h-pyrido[2,3-d]pyrimidin-2-one Chemical class C1=CN=C2NC(=O)N=CC2=C1 MHHOMHMNIRXARC-UHFFFAOYSA-N 0.000 description 1
BPMGYPAEPOYAMW-UHFFFAOYSA-N 2,3-dibromo-5-nitropyridine Chemical compound [O-][N+](=O)C1=CN=C(Br)C(Br)=C1 BPMGYPAEPOYAMW-UHFFFAOYSA-N 0.000 description 1
HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
NQVIIUBWMBHLOZ-UHFFFAOYSA-N 2-[2-hydroxyethyl-[6-[(4-methoxyphenyl)methylamino]-9-propan-2-ylpurin-2-yl]amino]ethanol Chemical compound C1=CC(OC)=CC=C1CNC1=NC(N(CCO)CCO)=NC2=C1N=CN2C(C)C NQVIIUBWMBHLOZ-UHFFFAOYSA-N 0.000 description 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
125000005925 3-methylpentyloxy group Chemical group 0.000 description 1
GXUQBVHIKVWWSN-UHFFFAOYSA-N 4-(5-aminopyridin-2-yl)piperazine-1-carboxylic acid Chemical compound N1=CC(N)=CC=C1N1CCN(C(O)=O)CC1 GXUQBVHIKVWWSN-UHFFFAOYSA-N 0.000 description 1
DWYVROKCLCUQMQ-UHFFFAOYSA-N 4-(5-nitropyridin-2-yl)piperazine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCN1C1=CC=C([N+]([O-])=O)C=N1 DWYVROKCLCUQMQ-UHFFFAOYSA-N 0.000 description 1
125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
ATXXLNCPVSUCNK-UHFFFAOYSA-N 5-bromo-2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)C=N1 ATXXLNCPVSUCNK-UHFFFAOYSA-N 0.000 description 1
YZSCPLGKKMSBMV-UHFFFAOYSA-N 5-fluoro-4-(8-fluoro-4-propan-2-yl-2,3-dihydro-1,4-benzoxazin-6-yl)-N-[5-(1-methylpiperidin-4-yl)pyridin-2-yl]pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)C1CCN(CC1)C)C1=CC2=C(OCCN2C(C)C)C(=C1)F YZSCPLGKKMSBMV-UHFFFAOYSA-N 0.000 description 1
125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
PCPLYCKSHDHXPE-UHFFFAOYSA-N 6-benzyl-2-[[6-(2-methoxyethoxy)pyridin-3-yl]amino]-5-methyl-8-propan-2-ylpyrido[2,3-d]pyrimidin-7-one Chemical compound C1=NC(OCCOC)=CC=C1NC1=NC=C(C(C)=C(CC=2C=CC=CC=2)C(=O)N2C(C)C)C2=N1 PCPLYCKSHDHXPE-UHFFFAOYSA-N 0.000 description 1
HDXKFGDHZPLADK-UHFFFAOYSA-N 6-bromo-8-cyclopentyl-2-methylsulfinylpyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(S(=O)C)=NC=C2C=C(Br)C(=O)N1C1CCCC1 HDXKFGDHZPLADK-UHFFFAOYSA-N 0.000 description 1
VVTSPTCBHTWXMD-UHFFFAOYSA-N 6-morpholin-4-ylpyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCOCC1 VVTSPTCBHTWXMD-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229910052686 Californium Inorganic materials 0.000 description 1
241000282465 Canis Species 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
102000002427 Cyclin B Human genes 0.000 description 1
108010068150 Cyclin B Proteins 0.000 description 1
102000003909 Cyclin E Human genes 0.000 description 1
108090000257 Cyclin E Proteins 0.000 description 1
108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 1
108700040267 Cyclin-Dependent Kinase Inhibitor Proteins Proteins 0.000 description 1
102000055246 Cyclin-Dependent Kinase Inhibitor Proteins Human genes 0.000 description 1
108010016788 Cyclin-Dependent Kinase Inhibitor p21 Proteins 0.000 description 1
102000000578 Cyclin-Dependent Kinase Inhibitor p21 Human genes 0.000 description 1
102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
230000033616 DNA repair Effects 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
208000007342 Diabetic Nephropathies Diseases 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
102100030011 Endoribonuclease Human genes 0.000 description 1
101710199605 Endoribonuclease Proteins 0.000 description 1
241000792859 Enema Species 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
241000282324 Felis Species 0.000 description 1
102000020897 Formins Human genes 0.000 description 1
108091022623 Formins Proteins 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
241000233866 Fungi Species 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
102000009465 Growth Factor Receptors Human genes 0.000 description 1
108010009202 Growth Factor Receptors Proteins 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
238000006130 Horner-Wadsworth-Emmons olefination reaction Methods 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 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
206010023203 Joint destruction Diseases 0.000 description 1
206010023232 Joint swelling Diseases 0.000 description 1
208000028257 Joubert syndrome with oculorenal defect Diseases 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000031888 Mycoses Diseases 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
208000034827 Neointima Diseases 0.000 description 1
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
108091008606 PDGF receptors Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
YNHIGQDRGKUECZ-UHFFFAOYSA-L PdCl2(PPh3)2 Substances [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
239000004264 Petrolatum Substances 0.000 description 1
241000223960 Plasmodium falciparum Species 0.000 description 1
102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
108010020346 Polyglutamic Acid Proteins 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
241000700159 Rattus Species 0.000 description 1
108091005682 Receptor kinases Proteins 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
239000004115 Sodium Silicate Substances 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
239000004141 Sodium laurylsulphate Substances 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
239000004147 Sorbitan trioleate Substances 0.000 description 1
PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
238000006619 Stille reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
238000006069 Suzuki reaction reaction Methods 0.000 description 1
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
230000001594 aberrant effect Effects 0.000 description 1
229940022663 acetate Drugs 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical class O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
238000002399 angioplasty Methods 0.000 description 1
150000001448 anilines Chemical class 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
229960005475 antiinfective agent Drugs 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
159000000032 aromatic acids Chemical class 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
208000035269 cancer or benign tumor Diseases 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000006315 carbonylation Effects 0.000 description 1
238000005810 carbonylation reaction Methods 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
101150059448 cdk7 gene Proteins 0.000 description 1
230000032823 cell division Effects 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
235000015111 chews Nutrition 0.000 description 1
KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
208000037893 chronic inflammatory disorder Diseases 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
238000010668 complexation reaction Methods 0.000 description 1
239000000306 component Substances 0.000 description 1
238000011109 contamination Methods 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
239000006071 cream Substances 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
125000000392 cycloalkenyl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
239000002254 cytotoxic agent Substances 0.000 description 1
231100000599 cytotoxic agent Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000007933 dermal patch Substances 0.000 description 1
238000013461 design Methods 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
UMNKXPULIDJLSU-UHFFFAOYSA-N dichlorofluoromethane Chemical compound FC(Cl)Cl UMNKXPULIDJLSU-UHFFFAOYSA-N 0.000 description 1
229940099364 dichlorofluoromethane Drugs 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000007907 direct compression Methods 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
229940126534 drug product Drugs 0.000 description 1
229940112141 dry powder inhaler Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000010410 dusting Methods 0.000 description 1
238000004520 electroporation Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940095399 enema Drugs 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
SNNHLSHDDGJVDM-UHFFFAOYSA-N ethyl 4-chloro-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1Cl SNNHLSHDDGJVDM-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000001125 extrusion Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000010408 film Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000012634 fragment Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
201000009277 hairy cell leukemia Diseases 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
229920002674 hyaluronan Polymers 0.000 description 1
229960003160 hyaluronic acid Drugs 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
125000001183 hydrocarbyl group Chemical group 0.000 description 1
239000000017 hydrogel Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000012678 infectious agent Substances 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
108091006086 inhibitor proteins Proteins 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000007915 intraurethral administration Methods 0.000 description 1
238000007914 intraventricular administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
230000007794 irritation Effects 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
210000002510 keratinocyte Anatomy 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
238000000021 kinase assay Methods 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
229940070765 laurate Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
229940099607 manganese chloride Drugs 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
229940095102 methyl benzoate Drugs 0.000 description 1
229960002900 methylcellulose Drugs 0.000 description 1
239000004530 micro-emulsion Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
239000011859 microparticle Substances 0.000 description 1
230000005012 migration Effects 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
239000011812 mixed powder Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000003607 modifier Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
230000003232 mucoadhesive effect Effects 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000002105 nanoparticle Substances 0.000 description 1
125000005487 naphthalate group Chemical group 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
230000008692 neointimal formation Effects 0.000 description 1
239000002353 niosome Substances 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
239000003921 oil Substances 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
229940039748 oxalate Drugs 0.000 description 1
125000004316 oxathiadiazolyl group Chemical group O1SNN=C1* 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000000466 oxiranyl group Chemical group 0.000 description 1
238000010651 palladium-catalyzed cross coupling reaction Methods 0.000 description 1
239000006201 parenteral dosage form Substances 0.000 description 1
239000003182 parenteral nutrition solution Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
230000035515 penetration Effects 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
229940066842 petrolatum Drugs 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
125000005545 phthalimidyl group Chemical group 0.000 description 1
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
239000004584 polyacrylic acid Substances 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
208000030761 polycystic kidney disease Diseases 0.000 description 1
229920000570 polyether Polymers 0.000 description 1
229920002643 polyglutamic acid Polymers 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
235000019422 polyvinyl alcohol Nutrition 0.000 description 1
229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
238000002203 pretreatment Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
239000000047 product Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
229940121649 protein inhibitor Drugs 0.000 description 1
239000012268 protein inhibitor Substances 0.000 description 1
244000000040 protozoan parasite Species 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
238000011552 rat model Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000037425 regulation of transcription Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
235000019337 sorbitan trioleate Nutrition 0.000 description 1
229960000391 sorbitan trioleate Drugs 0.000 description 1
238000001694 spray drying Methods 0.000 description 1
238000010922 spray-dried dispersion Methods 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000012289 standard assay Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
239000002511 suppository base 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
230000009747 swallowing Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
RMHRRMBFHGEDSR-UHFFFAOYSA-N tert-butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=N1 RMHRRMBFHGEDSR-UHFFFAOYSA-N 0.000 description 1
WWFJYZONBJARJT-UHFFFAOYSA-N tert-butyl 4-(5-nitropyridin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=N1 WWFJYZONBJARJT-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
238000003354 tissue distribution assay Methods 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
230000005748 tumor development Effects 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
108010064245 urinary gonadotropin fragment Proteins 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
229910000166 zirconium phosphate Inorganic materials 0.000 description 1