HRP20031080A2 - Tetrahydroquinoline derivatives - Google Patents

Info

Publication number

HRP20031080A2

HRP20031080A2 HR20031080A HRP20031080A HRP20031080A2 HR P20031080 A2 HRP20031080 A2 HR P20031080A2 HR 20031080 A HR20031080 A HR 20031080A HR P20031080 A HRP20031080 A HR P20031080A HR P20031080 A2 HRP20031080 A2 HR P20031080A2

Authority

HR

Croatia

Prior art keywords

alkyl

phenyl

acetyl

tetrahydro

trimethylquinoline

Prior art date

2001-07-02

Links

• Espacenet
• Global Dossier
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• 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 title 1
• 125000000217 alkyl group Chemical group 0.000 claims description 165
• 150000001875 compounds Chemical class 0.000 claims description 86
• 125000003118 aryl group Chemical group 0.000 claims description 49
• 125000003545 alkoxy group Chemical group 0.000 claims description 41
• 125000001072 heteroaryl group Chemical group 0.000 claims description 37
• -1 hydroxy, amino Chemical group 0.000 claims description 37
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 31
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
• 125000003342 alkenyl group Chemical group 0.000 claims description 19
• 125000000304 alkynyl group Chemical group 0.000 claims description 19
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 16
• 238000002360 preparation method Methods 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
• 229910052760 oxygen Inorganic materials 0.000 claims description 14
• 150000003530 tetrahydroquinolines Chemical class 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
• 229910052799 carbon Inorganic materials 0.000 claims description 10
• 150000003973 alkyl amines Chemical class 0.000 claims description 9
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
• 150000003839 salts Chemical class 0.000 claims description 8
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical group ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 7
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 7
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 125000003282 alkyl amino group Chemical group 0.000 claims description 6
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 6
• 125000005116 aryl carbamoyl group Chemical group 0.000 claims description 6
• 125000004104 aryloxy group Chemical group 0.000 claims description 6
• 125000005201 cycloalkylcarbonyloxy group Chemical group 0.000 claims description 6
• VMFDEEWJXWIULP-UHFFFAOYSA-N 1-(6-methoxy-2,2,4-trimethyl-4-phenyl-3h-quinolin-1-yl)ethanone Chemical compound C12=CC(OC)=CC=C2N(C(C)=O)C(C)(C)CC1(C)C1=CC=CC=C1 VMFDEEWJXWIULP-UHFFFAOYSA-N 0.000 claims description 5
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 230000035558 fertility Effects 0.000 claims description 5
• 125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 claims description 4
• 150000004982 aromatic amines Chemical class 0.000 claims description 4
• 125000005204 heteroarylcarbonyloxy group Chemical group 0.000 claims description 4
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
• IBPJOBWPZTZRQS-UHFFFAOYSA-N 1-(2,2,4,6,8-pentamethyl-4-phenyl-3h-quinolin-1-yl)ethanone Chemical compound C1C(C)(C)N(C(=O)C)C2=C(C)C=C(C)C=C2C1(C)C1=CC=CC=C1 IBPJOBWPZTZRQS-UHFFFAOYSA-N 0.000 claims description 3
• UHWQFJIDBCYRIB-UHFFFAOYSA-N 1-(2,2,4,6-tetramethyl-4-phenyl-3h-quinolin-1-yl)ethanone Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(C)C=C2C1(C)C1=CC=CC=C1 UHWQFJIDBCYRIB-UHFFFAOYSA-N 0.000 claims description 3
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
• ARWKEHPZVPYGDT-UHFFFAOYSA-N n-(1-acetyl-2,2,4-trimethyl-4-phenyl-3h-quinolin-6-yl)-2,2,2-trifluoroacetamide Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(NC(=O)C(F)(F)F)C=C2C1(C)C1=CC=CC=C1 ARWKEHPZVPYGDT-UHFFFAOYSA-N 0.000 claims description 3
• BMJCSYBLFOGGIA-UHFFFAOYSA-N n-[1-acetyl-2,2,4-trimethyl-4-(4-methylphenyl)-3h-quinolin-6-yl]-2,2,2-trifluoroacetamide Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(NC(=O)C(F)(F)F)C=C2C1(C)C1=CC=C(C)C=C1 BMJCSYBLFOGGIA-UHFFFAOYSA-N 0.000 claims description 3
• QWLACKLMUBWFKR-UHFFFAOYSA-N n-[1-acetyl-2,2,4-trimethyl-4-(4-methylphenyl)-3h-quinolin-6-yl]benzamide Chemical compound C1=C2C(C)(C=3C=CC(C)=CC=3)CC(C)(C)N(C(=O)C)C2=CC=C1NC(=O)C1=CC=CC=C1 QWLACKLMUBWFKR-UHFFFAOYSA-N 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• UMDRWEJVXXQRIZ-UHFFFAOYSA-N 2,2,4,6-tetramethyl-3,4,4a,5-tetrahydro-1h-quinoline Chemical compound C1=C(C)CC2C(C)CC(C)(C)NC2=C1 UMDRWEJVXXQRIZ-UHFFFAOYSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 description 161
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 120
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 98
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
• 238000004128 high performance liquid chromatography Methods 0.000 description 70
• 125000004432 carbon atom Chemical group C* 0.000 description 57
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 46
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 40
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• RTWPATFTOPMBPW-UHFFFAOYSA-N 1-(6-amino-2,2,4-trimethyl-4-phenyl-3h-quinolin-1-yl)ethanone Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(N)C=C2C1(C)C1=CC=CC=C1 RTWPATFTOPMBPW-UHFFFAOYSA-N 0.000 description 34
• 239000000203 mixture Substances 0.000 description 31
• 239000000243 solution Substances 0.000 description 30
• 238000005917 acylation reaction Methods 0.000 description 29
• 239000007821 HATU Substances 0.000 description 28
• 230000010933 acylation Effects 0.000 description 28
• 238000009833 condensation Methods 0.000 description 25
• 230000005494 condensation Effects 0.000 description 25
• 239000011541 reaction mixture Substances 0.000 description 25
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
• 235000019341 magnesium sulphate Nutrition 0.000 description 23
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 22
• 239000003480 eluent Substances 0.000 description 22
• 239000012044 organic layer Substances 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
• 238000004587 chromatography analysis Methods 0.000 description 20
• 239000000741 silica gel Substances 0.000 description 19
• 229910002027 silica gel Inorganic materials 0.000 description 19
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 18
• 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 17
• 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 17
• 230000002829 reductive effect Effects 0.000 description 17
• 102000005962 receptors Human genes 0.000 description 16
• 108020003175 receptors Proteins 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 229940028334 follicle stimulating hormone Drugs 0.000 description 15
• 125000005842 heteroatom Chemical group 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• 230000009471 action Effects 0.000 description 14
• XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 14
• 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 14
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 13
• 210000004027 cell Anatomy 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
• 102000008175 FSH Receptors Human genes 0.000 description 11
• 108010060374 FSH Receptors Proteins 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• 239000012267 brine Substances 0.000 description 10
• 229910052740 iodine Inorganic materials 0.000 description 10
• 235000017557 sodium bicarbonate Nutrition 0.000 description 10
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 239000011630 iodine Substances 0.000 description 9
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
• 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 8
• 230000027455 binding Effects 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• ZNRLMGFXSPUZNR-UHFFFAOYSA-N 2,2,4-trimethyl-1h-quinoline Chemical compound C1=CC=C2C(C)=CC(C)(C)NC2=C1 ZNRLMGFXSPUZNR-UHFFFAOYSA-N 0.000 description 7
• WVUMXBUVLLSUMD-UHFFFAOYSA-N 3-[(1-acetyl-2,2,4-trimethyl-4-phenyl-3h-quinolin-6-yl)amino]-3-oxopropanoic acid Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(NC(=O)CC(O)=O)C=C2C1(C)C1=CC=CC=C1 WVUMXBUVLLSUMD-UHFFFAOYSA-N 0.000 description 7
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
• 238000006069 Suzuki reaction reaction Methods 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 230000014509 gene expression Effects 0.000 description 7
• BALPUPABKHYFCR-UHFFFAOYSA-N n-(1-acetyl-2,2,4-trimethyl-4-phenyl-3h-quinolin-6-yl)-2-hydroxybenzamide Chemical compound C1=C2C(C)(C=3C=CC=CC=3)CC(C)(C)N(C(=O)C)C2=CC=C1NC(=O)C1=CC=CC=C1O BALPUPABKHYFCR-UHFFFAOYSA-N 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• GGIIQCYBWGKCMT-UHFFFAOYSA-N 1-acetyl-2,2,4-trimethyl-4-phenyl-3h-quinoline-6-carboxylic acid Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(C(O)=O)C=C2C1(C)C1=CC=CC=C1 GGIIQCYBWGKCMT-UHFFFAOYSA-N 0.000 description 6
• JPVUWCPKMYXOKW-UHFFFAOYSA-N 4-phenylbenzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1C1=CC=CC=C1 JPVUWCPKMYXOKW-UHFFFAOYSA-N 0.000 description 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• 108020004414 DNA Proteins 0.000 description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 108700008625 Reporter Genes Proteins 0.000 description 6
• 238000005614 Skraup synthesis reaction Methods 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• 239000013543 active substance Substances 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 239000012442 inert solvent Substances 0.000 description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 6
• IBZVSQSOMRCRCD-UHFFFAOYSA-N tert-butyl n-(1-acetyl-2,2,4-trimethylquinolin-6-yl)carbamate Chemical compound C1=C(NC(=O)OC(C)(C)C)C=C2C(C)=CC(C)(C)N(C(=O)C)C2=C1 IBZVSQSOMRCRCD-UHFFFAOYSA-N 0.000 description 6
• OZXIZRZFGJZWBF-UHFFFAOYSA-N 1,3,5-trimethyl-2-(2,4,6-trimethylphenoxy)benzene Chemical compound CC1=CC(C)=CC(C)=C1OC1=C(C)C=C(C)C=C1C OZXIZRZFGJZWBF-UHFFFAOYSA-N 0.000 description 5
• YIPDIHSVBRGRSA-UHFFFAOYSA-N 1-(6-hydroxy-2,2,4-trimethyl-4-phenyl-3h-quinolin-1-yl)ethanone Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(O)C=C2C1(C)C1=CC=CC=C1 YIPDIHSVBRGRSA-UHFFFAOYSA-N 0.000 description 5
• 102000006771 Gonadotropins Human genes 0.000 description 5
• 108010086677 Gonadotropins Proteins 0.000 description 5
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
• 239000012346 acetyl chloride Substances 0.000 description 5
• 230000003197 catalytic effect Effects 0.000 description 5
• 239000002622 gonadotropin Substances 0.000 description 5
• 229940094892 gonadotropins Drugs 0.000 description 5
• SHOJXDKTYKFBRD-UHFFFAOYSA-N mesityl oxide Natural products CC(C)=CC(C)=O SHOJXDKTYKFBRD-UHFFFAOYSA-N 0.000 description 5
• SAZUCVCMGQEWDD-UHFFFAOYSA-N n-(1-acetyl-2,2,4-trimethyl-4-phenyl-3h-quinolin-6-yl)-2-bromoacetamide Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(NC(=O)CBr)C=C2C1(C)C1=CC=CC=C1 SAZUCVCMGQEWDD-UHFFFAOYSA-N 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 230000000638 stimulation Effects 0.000 description 5
• LBUJPTNKIBCYBY-UHFFFAOYSA-N tetrahydroquinoline Natural products C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 150000001298 alcohols Chemical class 0.000 description 4
• 230000029936 alkylation Effects 0.000 description 4
• 238000005804 alkylation reaction Methods 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 230000017858 demethylation Effects 0.000 description 4
• 238000010520 demethylation reaction Methods 0.000 description 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
• 208000000509 infertility Diseases 0.000 description 4
• 230000036512 infertility Effects 0.000 description 4
• 231100000535 infertility Toxicity 0.000 description 4
• 150000002576 ketones Chemical class 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 230000016087 ovulation Effects 0.000 description 4
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
• 230000004936 stimulating effect Effects 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• JTNDKSZCEDNYRI-UHFFFAOYSA-N 1-(6-amino-2,2,4,7-tetramethyl-4-phenyl-3h-quinolin-1-yl)ethanone Chemical compound C1C(C)(C)N(C(=O)C)C2=CC(C)=C(N)C=C2C1(C)C1=CC=CC=C1 JTNDKSZCEDNYRI-UHFFFAOYSA-N 0.000 description 3
• UCSNTTGDGGCVRT-UHFFFAOYSA-N 1-(6-iodo-2,2,4-trimethyl-4-phenyl-3h-quinolin-1-yl)ethanone Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(I)C=C2C1(C)C1=CC=CC=C1 UCSNTTGDGGCVRT-UHFFFAOYSA-N 0.000 description 3
• DVDCSCQKHZSVFO-UHFFFAOYSA-N 1-[2-amino-1-methyl-4-(2,2,4-trimethyl-3,4-dihydroquinoline-1-carbonyl)cyclohexa-2,4-dien-1-yl]ethanone Chemical compound C12=CC=CC=C2C(C)CC(C)(C)N1C(=O)C1=CCC(C)(C(C)=O)C(N)=C1 DVDCSCQKHZSVFO-UHFFFAOYSA-N 0.000 description 3
• WVAXDHRFGWSJSE-UHFFFAOYSA-N 1-[4-(4-bromophenyl)-2,2,4,6-tetramethyl-3h-quinolin-1-yl]ethanone Chemical compound C1C(C)(C)N(C(=O)C)C2=CC=C(C)C=C2C1(C)C1=CC=C(Br)C=C1 WVAXDHRFGWSJSE-UHFFFAOYSA-N 0.000 description 3
• XESZUVZBAMCAEJ-UHFFFAOYSA-N 4-tert-butylcatechol Chemical compound CC(C)(C)C1=CC=C(O)C(O)=C1 XESZUVZBAMCAEJ-UHFFFAOYSA-N 0.000 description 3
• 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 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 229910015845 BBr3 Inorganic materials 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
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