ES2399047T3 - Derivados de piperazina y procedimiento de uso - Google Patents
Derivados de piperazina y procedimiento de uso Download PDFInfo
- Publication number
- ES2399047T3 ES2399047T3 ES03798936T ES03798936T ES2399047T3 ES 2399047 T3 ES2399047 T3 ES 2399047T3 ES 03798936 T ES03798936 T ES 03798936T ES 03798936 T ES03798936 T ES 03798936T ES 2399047 T3 ES2399047 T3 ES 2399047T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- aryl
- ethyl
- amide
- sulfonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- 150000004885 piperazines Chemical class 0.000 title description 5
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 117
- 125000003118 aryl group Chemical group 0.000 claims abstract description 83
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 82
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 63
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims abstract description 57
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 54
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 53
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 31
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 28
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 25
- 241000124008 Mammalia Species 0.000 claims abstract description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 21
- 230000036512 infertility Effects 0.000 claims abstract description 20
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims abstract description 18
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims abstract description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 13
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 13
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 125000002252 acyl group Chemical group 0.000 claims abstract description 11
- 125000005251 aryl acyl group Chemical group 0.000 claims abstract description 10
- 125000005253 heteroarylacyl group Chemical group 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 5
- -1 tetrahydro-beta-carbolinyl Chemical group 0.000 claims description 126
- 238000011282 treatment Methods 0.000 claims description 26
- 150000001408 amides Chemical class 0.000 claims description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 11
- RGBRTBPRPAKDDI-UHFFFAOYSA-N 1-ethyl-2-pyridin-3-ylbenzimidazol-5-amine Chemical compound N=1C2=CC(N)=CC=C2N(CC)C=1C1=CC=CN=C1 RGBRTBPRPAKDDI-UHFFFAOYSA-N 0.000 claims description 10
- SMWYBRZRHWKJIG-UHFFFAOYSA-N 4-thiophen-2-ylsulfonylpiperazine-1,3-dicarboxylic acid Chemical compound OC(=O)C1CN(C(O)=O)CCN1S(=O)(=O)C1=CC=CS1 SMWYBRZRHWKJIG-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- ZLVUKMURKLGYFK-UHFFFAOYSA-N 4-hexyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCCCC)CCN1S(=O)(=O)C1=CC=CS1 ZLVUKMURKLGYFK-UHFFFAOYSA-N 0.000 claims description 7
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 7
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 7
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims description 6
- 241000282414 Homo sapiens Species 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims description 6
- 108010018878 adenosine transporter Proteins 0.000 claims description 6
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 102000017953 prostanoid receptors Human genes 0.000 claims description 6
- 108050007059 prostanoid receptors Proteins 0.000 claims description 6
- MQVUYFZCYWYSGE-UHFFFAOYSA-N 4-(dimethylsulfamoyl)piperazine-1,3-dicarboxylic acid Chemical compound CN(C)S(=O)(=O)N1CCN(C(O)=O)CC1C(O)=O MQVUYFZCYWYSGE-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- QRGMOTHGSQFPPR-UHFFFAOYSA-N ethyl 2-[[3-[(9-ethylcarbazol-3-yl)carbamoyl]-4-thiophen-2-ylsulfonylpiperazine-1-carbonyl]amino]acetate Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1NC(=O)C1CN(C(=O)NCC(=O)OCC)CCN1S(=O)(=O)C1=CC=CS1 QRGMOTHGSQFPPR-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- KBQJOGGHUSNTAH-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-4-ylbenzimidazol-5-yl)-4-heptyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C1N(CCCCCCC)CCN(S(=O)(=O)C=2SC=CC=2)C1C(=O)NC(C=C1N=2)=CC=C1N(CC)C=2C1=CC=NC=C1 KBQJOGGHUSNTAH-UHFFFAOYSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- XJXPBTNJVJFKTH-UHFFFAOYSA-N 4-hexyl-n-(1-oxo-2,3,4,9-tetrahydropyrido[3,4-b]indol-6-yl)-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C=1C=C2NC(C(NCC3)=O)=C3C2=CC=1NC(=O)C1CN(CCCCCC)CCN1S(=O)(=O)C1=CC=CS1 XJXPBTNJVJFKTH-UHFFFAOYSA-N 0.000 claims description 3
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- IXPOWIFZZJWXKF-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-3-ylbenzimidazol-5-yl)-4-heptyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C1N(CCCCCCC)CCN(S(=O)(=O)C=2SC=CC=2)C1C(=O)NC(C=C1N=2)=CC=C1N(CC)C=2C1=CC=CN=C1 IXPOWIFZZJWXKF-UHFFFAOYSA-N 0.000 claims description 3
- YBMGPMVWMGAEJB-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-3-ylbenzimidazol-5-yl)-4-octyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C1N(CCCCCCCC)CCN(S(=O)(=O)C=2SC=CC=2)C1C(=O)NC(C=C1N=2)=CC=C1N(CC)C=2C1=CC=CN=C1 YBMGPMVWMGAEJB-UHFFFAOYSA-N 0.000 claims description 3
- DQGDKWCVYNHXBW-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-4-ylbenzimidazol-5-yl)-4-octyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C1N(CCCCCCCC)CCN(S(=O)(=O)C=2SC=CC=2)C1C(=O)NC(C=C1N=2)=CC=C1N(CC)C=2C1=CC=NC=C1 DQGDKWCVYNHXBW-UHFFFAOYSA-N 0.000 claims description 3
- KLKFSSZFJYHUJP-UHFFFAOYSA-N n-(9-ethylcarbazol-3-yl)-4-(3-methylsulfanylpropyl)-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1NC(=O)C1CN(CCCSC)CCN1S(=O)(=O)C1=CC=CS1 KLKFSSZFJYHUJP-UHFFFAOYSA-N 0.000 claims description 3
- SVSZTHONRDWNLA-UHFFFAOYSA-N n-(9-ethylcarbazol-3-yl)-4-hexyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1NC(=O)C1CN(CCCCCC)CCN1S(=O)(=O)C1=CC=CS1 SVSZTHONRDWNLA-UHFFFAOYSA-N 0.000 claims description 3
- RYMFVRHSGGEJNG-UHFFFAOYSA-N n-(9-ethylcarbazol-3-yl)-4-pentanoyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1NC(=O)C1CN(C(=O)CCCC)CCN1S(=O)(=O)C1=CC=CS1 RYMFVRHSGGEJNG-UHFFFAOYSA-N 0.000 claims description 3
- JSSXHAMIXJGYCS-UHFFFAOYSA-N piperazin-4-ium-2-carboxylate Chemical compound OC(=O)C1CNCCN1 JSSXHAMIXJGYCS-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- HQEZWSNNGYOFLC-UHFFFAOYSA-N 1-butylsulfonyl-n-(1-ethyl-2-pyridin-3-ylbenzimidazol-5-yl)-4-hexylpiperazine-2-carboxamide Chemical compound C1N(CCCCCC)CCN(S(=O)(=O)CCCC)C1C(=O)NC1=CC=C(N(CC)C(=N2)C=3C=NC=CC=3)C2=C1 HQEZWSNNGYOFLC-UHFFFAOYSA-N 0.000 claims description 2
- ZLFDWNSKVCLOJT-UHFFFAOYSA-N 6-amino-2,3,4,9-tetrahydropyrido[3,4-b]indol-1-one Chemical compound C12=CC(N)=CC=C2NC2=C1CCNC2=O ZLFDWNSKVCLOJT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 230000004720 fertilization Effects 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 2
- XKGLRBYJGDGECN-UHFFFAOYSA-N n-(1-oxo-2,3,4,9-tetrahydropyrido[3,4-b]indol-6-yl)-4-pentyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C=1C=C2NC(C(NCC3)=O)=C3C2=CC=1NC(=O)C1CN(CCCCC)CCN1S(=O)(=O)C1=CC=CS1 XKGLRBYJGDGECN-UHFFFAOYSA-N 0.000 claims description 2
- 230000000624 ovulatory effect Effects 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 3
- GGDSJWGRXIDGOH-UHFFFAOYSA-N 1-(dimethylsulfamoyl)-n-(1-ethyl-2-pyridin-3-ylbenzimidazol-5-yl)-4-hexylpiperazine-2-carboxamide Chemical compound C1N(CCCCCC)CCN(S(=O)(=O)N(C)C)C1C(=O)NC1=CC=C(N(CC)C(=N2)C=3C=NC=CC=3)C2=C1 GGDSJWGRXIDGOH-UHFFFAOYSA-N 0.000 claims 2
- 125000005257 alkyl acyl group Chemical group 0.000 claims 2
- WKHLARGJELRSPI-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-4-ylbenzimidazol-5-yl)-4-hexyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C1N(CCCCCC)CCN(S(=O)(=O)C=2SC=CC=2)C1C(=O)NC(C=C1N=2)=CC=C1N(CC)C=2C1=CC=NC=C1 WKHLARGJELRSPI-UHFFFAOYSA-N 0.000 claims 2
- YUCIWELSNXAUMI-UHFFFAOYSA-N n-(9-ethylcarbazol-3-yl)-4-[(4-ethylfuran-3-yl)methyl]-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound CCC1=COC=C1CN1CC(C(=O)NC=2C=C3C4=CC=CC=C4N(CC)C3=CC=2)N(S(=O)(=O)C=2SC=CC=2)CC1 YUCIWELSNXAUMI-UHFFFAOYSA-N 0.000 claims 2
- APDNSULKNJRTLZ-UHFFFAOYSA-N 1-(3-methylsulfanylpropyl)-4-thiophen-2-ylsulfonylpiperazine Chemical compound C1CN(CCCSC)CCN1S(=O)(=O)C1=CC=CS1 APDNSULKNJRTLZ-UHFFFAOYSA-N 0.000 claims 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims 1
- FYXUPGLCDBIDTF-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-3-ylbenzimidazol-5-yl)-1-(2-fluorophenyl)sulfonyl-4-hexylpiperazine-2-carboxamide Chemical compound C1N(CCCCCC)CCN(S(=O)(=O)C=2C(=CC=CC=2)F)C1C(=O)NC(C=C1N=2)=CC=C1N(CC)C=2C1=CC=CN=C1 FYXUPGLCDBIDTF-UHFFFAOYSA-N 0.000 claims 1
- VDZJKCNGLBILED-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-3-ylbenzimidazol-5-yl)-1-(4-fluorophenyl)sulfonyl-4-hexylpiperazine-2-carboxamide Chemical compound C1N(CCCCCC)CCN(S(=O)(=O)C=2C=CC(F)=CC=2)C1C(=O)NC(C=C1N=2)=CC=C1N(CC)C=2C1=CC=CN=C1 VDZJKCNGLBILED-UHFFFAOYSA-N 0.000 claims 1
- 230000000920 spermatogeneic effect Effects 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 abstract description 4
- 125000005281 alkyl ureido group Chemical group 0.000 abstract description 3
- 208000000509 infertility Diseases 0.000 description 16
- 208000021267 infertility disease Diseases 0.000 description 16
- 108020003175 receptors Proteins 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 16
- 125000001424 substituent group Chemical group 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 125000003107 substituted aryl group Chemical group 0.000 description 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- BRYCUMKDWMEGMK-UHFFFAOYSA-N piperazine-2-carboxamide Chemical class NC(=O)C1CNCCN1 BRYCUMKDWMEGMK-UHFFFAOYSA-N 0.000 description 7
- 125000004193 piperazinyl group Chemical group 0.000 description 7
- 230000021595 spermatogenesis Effects 0.000 description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 206010021928 Infertility female Diseases 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 150000002367 halogens Chemical group 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 description 6
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 5
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 229940028334 follicle stimulating hormone Drugs 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 238000004020 luminiscence type Methods 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 208000037765 diseases and disorders Diseases 0.000 description 3
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical class NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- GNFQUNPEZPQPLK-UHFFFAOYSA-N 1-(4-fluorophenyl)sulfonyl-4-hexylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCCCC)CCN1S(=O)(=O)C1=CC=C(F)C=C1 GNFQUNPEZPQPLK-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 2
- UKGBLGIYYXJYRJ-UHFFFAOYSA-N 4-heptyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCCCCC)CCN1S(=O)(=O)C1=CC=CS1 UKGBLGIYYXJYRJ-UHFFFAOYSA-N 0.000 description 2
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- 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 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 102000011923 Thyrotropin Human genes 0.000 description 2
- 108010061174 Thyrotropin Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 2
- 210000004198 anterior pituitary gland Anatomy 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000001720 carbohydrates Chemical group 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 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 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- WNSDZBQLMGKPQS-RZFWHQLPSA-N (2r)-piperazine-1,4-diium-2-carboxylic acid;dichloride Chemical compound Cl.Cl.OC(=O)[C@H]1CNCCN1 WNSDZBQLMGKPQS-RZFWHQLPSA-N 0.000 description 1
- SUDYQKKBKMGXKU-SCSAIBSYSA-N (3r)-piperazine-1,3-dicarboxylic acid Chemical compound OC(=O)[C@H]1CN(C(O)=O)CCN1 SUDYQKKBKMGXKU-SCSAIBSYSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- JSSXHAMIXJGYCS-SCSAIBSYSA-N (R)-piperazine-2-carboxylic acid Chemical compound [O-]C(=O)[C@H]1CNCC[NH2+]1 JSSXHAMIXJGYCS-SCSAIBSYSA-N 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- UIWRYQDMDJHZMV-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-hexylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCCCC)CCN1S(=O)(=O)C1=CC=CC=C1 UIWRYQDMDJHZMV-UHFFFAOYSA-N 0.000 description 1
- OSLISCVTIVCMPN-UHFFFAOYSA-N 1-(dimethylsulfamoyl)-4-hexylpiperazine-2-carboxylic acid Chemical compound CCCCCCN1CCN(S(=O)(=O)N(C)C)C(C(O)=O)C1 OSLISCVTIVCMPN-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 1
- PYTMYKVIJXPNBD-OQKDUQJOSA-N 2-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylethanamine;hydron;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 PYTMYKVIJXPNBD-OQKDUQJOSA-N 0.000 description 1
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- HQNOODJDSFSURF-UHFFFAOYSA-N 3-(1h-imidazol-2-yl)propan-1-amine Chemical compound NCCCC1=NC=CN1 HQNOODJDSFSURF-UHFFFAOYSA-N 0.000 description 1
- OTHOHJOUNPURSA-UHFFFAOYSA-N 4-(3-methylsulfanylpropyl)-1-thiophen-2-ylsulfonylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCSC)CCN1S(=O)(=O)C1=CC=CS1 OTHOHJOUNPURSA-UHFFFAOYSA-N 0.000 description 1
- KYXKVPFGASJBQX-UHFFFAOYSA-N 4-[(4-ethylfuran-3-yl)methyl]-1-thiophen-2-ylsulfonylpiperazine-2-carboxylic acid Chemical compound CCC1=COC=C1CN1CC(C(O)=O)N(S(=O)(=O)C=2SC=CC=2)CC1 KYXKVPFGASJBQX-UHFFFAOYSA-N 0.000 description 1
- UYYVPOWNUMEMKS-UHFFFAOYSA-N 4-heptyl-n-(1-oxo-2,3,4,9-tetrahydropyrido[3,4-b]indol-6-yl)-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C=1C=C2NC(C(NCC3)=O)=C3C2=CC=1NC(=O)C1CN(CCCCCCC)CCN1S(=O)(=O)C1=CC=CS1 UYYVPOWNUMEMKS-UHFFFAOYSA-N 0.000 description 1
- DMAKLTIYDYMFGI-UHFFFAOYSA-N 4-octyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCCCCCC)CCN1S(=O)(=O)C1=CC=CS1 DMAKLTIYDYMFGI-UHFFFAOYSA-N 0.000 description 1
- MVVJHVNFNNWUTQ-UHFFFAOYSA-N 4-pentanoyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(C(=O)CCCC)CCN1S(=O)(=O)C1=CC=CS1 MVVJHVNFNNWUTQ-UHFFFAOYSA-N 0.000 description 1
- TXBMBNXHXAHWQS-UHFFFAOYSA-N 4-pentyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCCC)CCN1S(=O)(=O)C1=CC=CS1 TXBMBNXHXAHWQS-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- OXEUETBFKVCRNP-UHFFFAOYSA-N 9-ethyl-3-carbazolamine Chemical compound NC1=CC=C2N(CC)C3=CC=CC=C3C2=C1 OXEUETBFKVCRNP-UHFFFAOYSA-N 0.000 description 1
- PLAZXGNBGZYJSA-UHFFFAOYSA-N 9-ethylcarbazole Chemical compound C1=CC=C2N(CC)C3=CC=CC=C3C2=C1 PLAZXGNBGZYJSA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108700012941 GNRH1 Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 108091006065 Gs proteins Proteins 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 229920005479 Lucite® Polymers 0.000 description 1
- 108010057021 Menotropins Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- UGJBHEZMOKVTIM-UHFFFAOYSA-N N-formylglycine Chemical compound OC(=O)CNC=O UGJBHEZMOKVTIM-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000006877 Pituitary Hormones Human genes 0.000 description 1
- 108010047386 Pituitary Hormones Proteins 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 description 1
- 108010047196 Urofollitropin Proteins 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000005055 alkyl alkoxy group Chemical group 0.000 description 1
- 125000005157 alkyl carboxy group Chemical group 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000007854 aminals Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 150000005524 benzylchlorides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000003857 carboxamides Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940046989 clomiphene citrate Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000004246 corpus luteum Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([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
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000019961 diglycerides of fatty acid Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 230000008217 follicular development Effects 0.000 description 1
- 108010006578 follitropin alfa Proteins 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000006543 gametophyte development Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 229940057854 gonal f Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000000960 hypophysis hormone Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000005990 isobenzothienyl group Chemical group 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
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 210000002332 leydig cell Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 235000019960 monoglycerides of fatty acid Nutrition 0.000 description 1
- ACGNLMWVUQRAQQ-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-3-ylbenzimidazol-5-yl)-4-hexyl-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C1N(CCCCCC)CCN(S(=O)(=O)C=2SC=CC=2)C1C(=O)NC(C=C1N=2)=CC=C1N(CC)C=2C1=CC=CN=C1 ACGNLMWVUQRAQQ-UHFFFAOYSA-N 0.000 description 1
- ZQBCWQGVLGLDJI-UHFFFAOYSA-N n-(1-ethyl-2-pyridin-4-ylbenzimidazol-5-yl)-4-(3-methylsulfanylpropyl)-1-thiophen-2-ylsulfonylpiperazine-2-carboxamide Chemical compound C=1C=C2N(CC)C(C=3C=CN=CC=3)=NC2=CC=1NC(=O)C1CN(CCCSC)CCN1S(=O)(=O)C1=CC=CS1 ZQBCWQGVLGLDJI-UHFFFAOYSA-N 0.000 description 1
- FRLCQIRNLBDGNF-UHFFFAOYSA-N n-(2-ethoxyethyl)formamide Chemical compound CCOCCNC=O FRLCQIRNLBDGNF-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-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
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 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
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000007683 regulation of progesterone secretion Effects 0.000 description 1
- 230000027272 reproductive process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002863 seminiferous tubule Anatomy 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 235000012222 talc Nutrition 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
- 238000010998 test method Methods 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41230802P | 2002-09-20 | 2002-09-20 | |
| US412308P | 2002-09-20 | ||
| PCT/EP2003/050640 WO2004031182A1 (en) | 2002-09-20 | 2003-09-19 | Piperazine derivatives and methods of use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2399047T3 true ES2399047T3 (es) | 2013-03-25 |
Family
ID=32069711
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03798936T Expired - Lifetime ES2399047T3 (es) | 2002-09-20 | 2003-09-19 | Derivados de piperazina y procedimiento de uso |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US7754722B2 (enExample) |
| EP (1) | EP1542993B1 (enExample) |
| JP (2) | JP4713152B2 (enExample) |
| AU (1) | AU2003299124A1 (enExample) |
| CA (1) | CA2499732A1 (enExample) |
| ES (1) | ES2399047T3 (enExample) |
| NO (1) | NO20051844L (enExample) |
| WO (1) | WO2004031182A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1592389B1 (en) | 2003-02-14 | 2009-04-22 | Laboratoires Serono SA | Piperazine-2-carboxamide derivatives |
| US8017612B2 (en) | 2006-04-18 | 2011-09-13 | Japan Tobacco Inc. | Piperazine compound and use thereof as a HCV polymerase inhibitor |
| TW200944523A (en) * | 2008-02-08 | 2009-11-01 | Organon Nv | (Dihydro)pyrrolo[2,1-a]isoquinolines |
| US8071587B2 (en) | 2009-05-27 | 2011-12-06 | N. V. Organon | (Dihydro)imidazoiso[5,1-A]quinolines |
| TW201116531A (en) | 2009-07-29 | 2011-05-16 | Organon Nv | Ring-annulated dihydropyrrolo[2,1-a]isoquinolines |
| US8431564B2 (en) | 2009-07-29 | 2013-04-30 | Merck Sharp & Dohme B.V. | Ring-annulated dihydropyrrolo[2,1-α]isoquinolines |
| TW201116515A (en) | 2009-07-31 | 2011-05-16 | Organon Nv | Dihydrobenzoindazoles |
| CA2801074A1 (en) | 2010-06-04 | 2011-12-08 | Albany Molecular Research, Inc. | Glycine transporter-1 inhibitors, methods of making them, and uses thereof |
| JP6162694B2 (ja) * | 2011-07-18 | 2017-07-12 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | ベンズアミド類 |
| AR095202A1 (es) * | 2013-03-11 | 2015-09-30 | Merck Patent Gmbh | Heterociclos como moduladores de la actividad quinasa |
| KR20170054650A (ko) * | 2015-11-10 | 2017-05-18 | 삼성전자주식회사 | 이동 정보에 기초하여 심박수를 추정하는 방법 및 장치 |
| US10688224B1 (en) | 2019-07-03 | 2020-06-23 | King Abdulaziz University | Prosthetic implantable antibacterial surgical mesh |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5639639A (en) * | 1983-11-02 | 1997-06-17 | Genzyme Corporation | Recombinant heterodimeric human fertility hormones, and methods, cells, vectors and DNA for the production thereof |
| IT1206302B (it) * | 1987-06-26 | 1989-04-14 | Serono Cesare Ist Ricerca | Ormone follicolo-stimolante urinario |
| US5017557A (en) * | 1987-07-24 | 1991-05-21 | Industria Farmaceutica Serono S.P.A. | Treatment of infertility with somatotrophin releasing factor |
| IL117798A (en) * | 1995-04-07 | 2001-11-25 | Schering Plough Corp | Tricyclic compounds useful for inhibiting the function of protein - G and for the treatment of malignant diseases, and pharmaceutical preparations containing them |
| US5880128A (en) * | 1996-05-08 | 1999-03-09 | Schering Corporation | Carbonyl piperazinyl and piperidinyl compounds |
| ES2224408T3 (es) | 1997-06-17 | 2005-03-01 | Schering Corporation | Compuestos de benzopiridocicloheptano utiles para la inhibicion de la farnesil-proteina-transferasa. |
| ES2221227T3 (es) | 1997-11-24 | 2004-12-16 | MERCK & CO., INC. | Derivados sustituidos de beta-alanina como inhibidores de la adhesion celular. |
| PT1102763E (pt) | 1998-08-07 | 2005-01-31 | Applied Research Systems | Mimeticos fsh para o tratamento da infertilidade |
| US6432959B1 (en) * | 1998-12-23 | 2002-08-13 | Schering Corporation | Inhibitors of farnesyl-protein transferase |
| ES2242444T3 (es) * | 1998-12-23 | 2005-11-01 | Schering Corporation | Nuevos inhibidores de la farnesil-proteina-transferasa. |
| US6426357B1 (en) * | 1999-07-27 | 2002-07-30 | Affymax, Inc. | Antagonists of follicle stimulating hormone activity |
| JP2001294572A (ja) | 2000-02-09 | 2001-10-23 | Dai Ichi Seiyaku Co Ltd | 新規スルホニル誘導体 |
| WO2002009706A1 (en) | 2000-07-27 | 2002-02-07 | Smithkline Beecham Corporation | Agonists of follicle stimulating hormone activity |
| EP1592389B1 (en) * | 2003-02-14 | 2009-04-22 | Laboratoires Serono SA | Piperazine-2-carboxamide derivatives |
-
2003
- 2003-09-19 AU AU2003299124A patent/AU2003299124A1/en not_active Abandoned
- 2003-09-19 CA CA002499732A patent/CA2499732A1/en not_active Abandoned
- 2003-09-19 ES ES03798936T patent/ES2399047T3/es not_active Expired - Lifetime
- 2003-09-19 US US10/528,437 patent/US7754722B2/en not_active Expired - Fee Related
- 2003-09-19 JP JP2004540809A patent/JP4713152B2/ja not_active Expired - Fee Related
- 2003-09-19 WO PCT/EP2003/050640 patent/WO2004031182A1/en not_active Ceased
- 2003-09-19 EP EP03798936A patent/EP1542993B1/en not_active Expired - Lifetime
-
2005
- 2005-04-15 NO NO20051844A patent/NO20051844L/no not_active Application Discontinuation
-
2010
- 2010-06-02 US US12/792,665 patent/US20100305137A1/en not_active Abandoned
-
2011
- 2011-01-04 JP JP2011000050A patent/JP5436462B2/ja not_active Expired - Fee Related
-
2013
- 2013-01-30 US US13/754,345 patent/US8946227B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2499732A1 (en) | 2004-04-15 |
| US8946227B2 (en) | 2015-02-03 |
| EP1542993B1 (en) | 2012-12-19 |
| JP4713152B2 (ja) | 2011-06-29 |
| JP5436462B2 (ja) | 2014-03-05 |
| EP1542993A1 (en) | 2005-06-22 |
| AU2003299124A1 (en) | 2004-04-23 |
| US20060223813A1 (en) | 2006-10-05 |
| US20100305137A1 (en) | 2010-12-02 |
| US7754722B2 (en) | 2010-07-13 |
| WO2004031182A1 (en) | 2004-04-15 |
| US20130143893A1 (en) | 2013-06-06 |
| NO20051844L (no) | 2005-04-15 |
| JP2011088926A (ja) | 2011-05-06 |
| JP2006503857A (ja) | 2006-02-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5436462B2 (ja) | ピペラジン誘導体及び使用方法 | |
| AU2021250993B2 (en) | Aryl receptor modulators and methods of making and using the same | |
| ES2857549T3 (es) | Ligandos de receptores de opioides y métodos para utilizar y obtener los mismos | |
| ES2276803T3 (es) | Inhibidores de polimerasa viral. | |
| CN111511729A (zh) | Tlr7/8拮抗剂及其用途 | |
| BR112019011801A2 (pt) | composto, composição farmacêutica e método de inibição de dlk, método de tratamento de uma doença mediada por dlk, método de tratamento de câncer e redução do desenvolvimento de um distúrbio neurológico induzido por quimioterapia e método para alcançar um efeito em um paciente | |
| CN104606194A (zh) | Pde4的双环杂芳基抑制剂 | |
| JP2023029899A (ja) | 同種抗体により駆動される慢性移植片対宿主病を処置及び予防する方法 | |
| CN107973790A (zh) | 杂环fxr调节剂 | |
| SA06270148B1 (ar) | مثبطات إنزيم تيروسين كيناز | |
| CN102186479A (zh) | 用于治疗疾病的组胺受体的氨基嘧啶抑制剂 | |
| BR112020019824A2 (pt) | Composto de fórmula estrutural i ou um sal do mesmo, composição farmacêutica, método de inibição de cbp, método de inibição de p300, método de tratamento de uma doença mediada por cbp, método de tratamento de uma doença mediada por p300 e método para alcançar um efeito em um paciente | |
| JP2016501883A (ja) | デングウイルス感染症の治療及び予防のためのチエノピリジン誘導体 | |
| ES2243504T3 (es) | Uso de derivados de pirazol para tratar la infertilidad. | |
| CN107973834A (zh) | 作为fxr/tgr5调节剂的胆酸衍生物 | |
| TWI228508B (en) | Thieno[2,3-d]pyrimidines with combined LH and FSH agonistic activity | |
| JP6333826B2 (ja) | アザインドリン | |
| ES2657979T3 (es) | Compuestos de imidazol como moduladores de FSHR y sus usos | |
| ES2273487T3 (es) | Antagonistas a1 de adenosina contra la esterilidad masculina. | |
| JP2002503661A (ja) | 性腺刺激ホルモン放出ホルモン拮抗薬 | |
| ES2232736T3 (es) | Derivados de naftostrilos y su empleo como inhibidores de kinasas dependientes de ciclina. | |
| ES2347681T3 (es) | Agentes para tratar el herpes genital despues de su aparicion. | |
| AU2011265521B9 (en) | JNK inhibitors for the treatment of endometreosis | |
| Magnolol | Magnesium carbonate-Magnolol | |
| CN101528228A (zh) | Pde4的双环杂芳基抑制剂 |