CA2946754C - Optically active pde10 inhibitor - Google Patents
Optically active pde10 inhibitor Download PDFInfo
- Publication number
- CA2946754C CA2946754C CA2946754A CA2946754A CA2946754C CA 2946754 C CA2946754 C CA 2946754C CA 2946754 A CA2946754 A CA 2946754A CA 2946754 A CA2946754 A CA 2946754A CA 2946754 C CA2946754 C CA 2946754C
- Authority
- CA
- Canada
- Prior art keywords
- disorders
- compound
- neurological disorder
- disease
- animal
- 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.)
- Active
Links
- 239000003112 inhibitor Substances 0.000 title description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 161
- 239000000203 mixture Substances 0.000 claims description 31
- 208000012902 Nervous system disease Diseases 0.000 claims description 27
- 241001465754 Metazoa Species 0.000 claims description 25
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 14
- 206010015037 epilepsy Diseases 0.000 claims description 12
- 201000000980 schizophrenia Diseases 0.000 claims description 12
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 10
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 208000024254 Delusional disease Diseases 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 208000028017 Psychotic disease Diseases 0.000 claims description 7
- 208000011963 Substance-induced psychotic disease Diseases 0.000 claims description 7
- 231100000393 Substance-induced psychotic disorder Toxicity 0.000 claims description 7
- 201000002545 drug psychosis Diseases 0.000 claims description 7
- 208000019906 panic disease Diseases 0.000 claims description 7
- 208000002851 paranoid schizophrenia Diseases 0.000 claims description 7
- 230000005855 radiation Effects 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 6
- 206010003805 Autism Diseases 0.000 claims description 6
- 208000020706 Autistic disease Diseases 0.000 claims description 6
- 208000006373 Bell palsy Diseases 0.000 claims description 6
- 208000020925 Bipolar disease Diseases 0.000 claims description 6
- 206010012289 Dementia Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 6
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 6
- 208000016620 Tourette disease Diseases 0.000 claims description 6
- 208000036826 VIIth nerve paralysis Diseases 0.000 claims description 6
- 201000007201 aphasia Diseases 0.000 claims description 6
- 206010008129 cerebral palsy Diseases 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 206010014599 encephalitis Diseases 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 208000019899 phobic disease Diseases 0.000 claims description 6
- 208000019116 sleep disease Diseases 0.000 claims description 6
- 208000027448 Attention Deficit and Disruptive Behavior disease Diseases 0.000 claims description 5
- 208000035548 disruptive behavior disease Diseases 0.000 claims description 5
- 229910016523 CuKa Inorganic materials 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 abstract description 105
- 230000008569 process Effects 0.000 abstract description 85
- 239000013078 crystal Substances 0.000 abstract description 15
- 239000000543 intermediate Substances 0.000 abstract description 10
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- QQHJRLKSCSRMEM-DEOSSOPVSA-N ClC1=C(C=C(C=C1OC)C1=CC=C(O1)C([C@H](C1=CC=C(C=C1)C=1SC(=NN1)C)OCC)=O)OC Chemical compound ClC1=C(C=C(C=C1OC)C1=CC=C(O1)C([C@H](C1=CC=C(C=C1)C=1SC(=NN1)C)OCC)=O)OC QQHJRLKSCSRMEM-DEOSSOPVSA-N 0.000 abstract 5
- QQHJRLKSCSRMEM-UHFFFAOYSA-N 1-[5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl]-2-ethoxy-2-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]ethanone Chemical compound C=1C=C(C=2SC(C)=NN=2)C=CC=1C(OCC)C(=O)C(O1)=CC=C1C1=CC(OC)=C(Cl)C(OC)=C1 QQHJRLKSCSRMEM-UHFFFAOYSA-N 0.000 abstract 1
- -1 -(CH2)50(CH2)õ Chemical group 0.000 description 34
- 229910052751 metal Inorganic materials 0.000 description 29
- 239000002184 metal Substances 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 21
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 150000003839 salts Chemical class 0.000 description 18
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 17
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 230000008878 coupling Effects 0.000 description 14
- 238000010168 coupling process Methods 0.000 description 14
- 238000005859 coupling reaction Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000012453 solvate Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 11
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 11
- 229910052744 lithium Inorganic materials 0.000 description 11
- 230000003389 potentiating effect Effects 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- 239000011777 magnesium Substances 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102100039856 Histone H1.1 Human genes 0.000 description 9
- 101001035402 Homo sapiens Histone H1.1 Proteins 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 9
- 229910052802 copper Inorganic materials 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 125000000129 anionic group Chemical group 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 229960005017 olanzapine Drugs 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- 239000000376 reactant Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 208000025966 Neurological disease Diseases 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 238000007333 cyanation reaction Methods 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 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 5
- 102000016267 Leptin Human genes 0.000 description 5
- 108010092277 Leptin Proteins 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 5
- 229940039781 leptin Drugs 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical group C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000007171 acid catalysis Methods 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000009435 amidation Effects 0.000 description 4
- 238000007112 amidation reaction Methods 0.000 description 4
- 150000005840 aryl radicals Chemical class 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000004296 chiral HPLC Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000037406 food intake Effects 0.000 description 4
- 235000012631 food intake Nutrition 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 4
- 238000010189 synthetic method Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical group CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 101100351286 Dictyostelium discoideum pdeE gene Proteins 0.000 description 3
- 101100135859 Dictyostelium discoideum regA gene Proteins 0.000 description 3
- 102000012074 GAF domains Human genes 0.000 description 3
- 108050002598 GAF domains Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 description 3
- 101100082606 Plasmodium falciparum (isolate 3D7) PDEbeta gene Proteins 0.000 description 3
- 101100135860 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PDE2 gene Proteins 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 239000000164 antipsychotic agent Substances 0.000 description 3
- 229940005529 antipsychotics Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthene Chemical group C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 101150037969 pde-6 gene Proteins 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- PUJSZNONTPWTHD-UHFFFAOYSA-N 2-(4-chloro-3,5-dimethoxyphenyl)furan Chemical compound COC1=C(Cl)C(OC)=CC(C=2OC=CC=2)=C1 PUJSZNONTPWTHD-UHFFFAOYSA-N 0.000 description 2
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 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 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 208000016285 Movement disease Diseases 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 101150098694 PDE5A gene Proteins 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical group C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 239000012911 assay medium Substances 0.000 description 2
- 239000003693 atypical antipsychotic agent Substances 0.000 description 2
- 229940127236 atypical antipsychotics Drugs 0.000 description 2
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical group C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- WDECIBYCCFPHNR-UHFFFAOYSA-N chrysene Chemical group C1=CC=CC2=CC=C3C4=CC=CC=C4C=CC3=C21 WDECIBYCCFPHNR-UHFFFAOYSA-N 0.000 description 2
- 150000001868 cobalt Chemical class 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000013480 data collection Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- LBVQLNOQOXKBSE-UHFFFAOYSA-N heptane;propan-2-yl acetate Chemical compound CCCCCCC.CC(C)OC(C)=O LBVQLNOQOXKBSE-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910001507 metal halide Inorganic materials 0.000 description 2
- 150000005309 metal halides Chemical class 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical group C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000006187 pill 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
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical group C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000006023 1-pentenyl group Chemical group 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- NSMKWTGDPQHTDH-UHFFFAOYSA-N 2-bromo-5-methyl-1,3,4-thiadiazole Chemical compound CC1=NN=C(Br)S1 NSMKWTGDPQHTDH-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 108010054479 3',5'-Cyclic-AMP Phosphodiesterases Proteins 0.000 description 1
- 102000001707 3',5'-Cyclic-AMP Phosphodiesterases Human genes 0.000 description 1
- 125000006027 3-methyl-1-butenyl group Chemical group 0.000 description 1
- USWUGTKXFNKMQE-UHFFFAOYSA-N 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzaldehyde Chemical compound S1C(C)=NN=C1C1=CC=C(C=O)C=C1 USWUGTKXFNKMQE-UHFFFAOYSA-N 0.000 description 1
- NMOAOMYTJQDCES-UHFFFAOYSA-N 5-bromo-2-chloro-1,3-dimethoxybenzene Chemical compound COC1=CC(Br)=CC(OC)=C1Cl NMOAOMYTJQDCES-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000192542 Anabaena Species 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102100024316 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Human genes 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
- 101100407340 Drosophila melanogaster Pde8 gene Proteins 0.000 description 1
- 101100407341 Drosophila melanogaster Pde9 gene Proteins 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 102100024233 High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A Human genes 0.000 description 1
- 101001117044 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Proteins 0.000 description 1
- 101001117267 Homo sapiens High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A Proteins 0.000 description 1
- 101001098858 Homo sapiens cGMP-dependent 3',5'-cyclic phosphodiesterase Proteins 0.000 description 1
- 101001098818 Homo sapiens cGMP-inhibited 3',5'-cyclic phosphodiesterase A Proteins 0.000 description 1
- 101000988412 Homo sapiens cGMP-specific 3',5'-cyclic phosphodiesterase Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101100407337 Mus musculus Pde8a gene Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- SLGBZMMZGDRARJ-UHFFFAOYSA-N Triphenylene Chemical group C1=CC=C2C3=CC=CC=C3C3=CC=CC=C3C2=C1 SLGBZMMZGDRARJ-UHFFFAOYSA-N 0.000 description 1
- 231100000230 acceptable toxicity Toxicity 0.000 description 1
- JDPAVWAQGBGGHD-UHFFFAOYSA-N aceanthrylene Chemical group C1=CC=C2C(C=CC3=CC=C4)=C3C4=CC2=C1 JDPAVWAQGBGGHD-UHFFFAOYSA-N 0.000 description 1
- 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- SQFPKRNUGBRTAR-UHFFFAOYSA-N acephenanthrylene Chemical group C1=CC(C=C2)=C3C2=CC2=CC=CC=C2C3=C1 SQFPKRNUGBRTAR-UHFFFAOYSA-N 0.000 description 1
- HXGDTGSAIMULJN-UHFFFAOYSA-N acetnaphthylene Chemical group C1=CC(C=C2)=C3C2=CC=CC3=C1 HXGDTGSAIMULJN-UHFFFAOYSA-N 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- KNNXFYIMEYKHBZ-UHFFFAOYSA-N as-indacene Chemical group C1=CC2=CC=CC2=C2C=CC=C21 KNNXFYIMEYKHBZ-UHFFFAOYSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 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
- WGQKYBSKWIADBV-UHFFFAOYSA-O benzylaminium Chemical compound [NH3+]CC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-O 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 102100038953 cGMP-dependent 3',5'-cyclic phosphodiesterase Human genes 0.000 description 1
- 102100037093 cGMP-inhibited 3',5'-cyclic phosphodiesterase A Human genes 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 231100000762 chronic effect Toxicity 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 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
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000019439 energy homeostasis Effects 0.000 description 1
- TWAOQVMPIYQPKG-UHFFFAOYSA-N ethanone Chemical compound C[C+]=O TWAOQVMPIYQPKG-UHFFFAOYSA-N 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 125000005469 ethylenyl group Chemical group 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
- 101150060381 fhlA gene Proteins 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical group C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 229960002690 fluphenazine Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 150000002307 glutamic acids Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910001411 inorganic cation Inorganic materials 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 125000005468 isobutylenyl group Chemical group 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 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
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 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
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 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
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Chemical group C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NQFOGDIWKQWFMN-UHFFFAOYSA-N phenalene Chemical group C1=CC([CH]C=C2)=C3C2=CC=CC3=C1 NQFOGDIWKQWFMN-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- DIJNSQQKNIVDPV-UHFFFAOYSA-N pleiadene Chemical group C1=C2[CH]C=CC=C2C=C2C=CC=C3[C]2C1=CC=C3 DIJNSQQKNIVDPV-UHFFFAOYSA-N 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000005470 propylenyl group Chemical group 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 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
- 229960004431 quetiapine Drugs 0.000 description 1
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- WEMQMWWWCBYPOV-UHFFFAOYSA-N s-indacene Chemical group C=1C2=CC=CC2=CC2=CC=CC2=1 WEMQMWWWCBYPOV-UHFFFAOYSA-N 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 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
- 238000000926 separation method Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000003998 snake venom Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 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
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000005580 triphenylene group Chemical group 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 238000012982 x-ray structure analysis Methods 0.000 description 1
- 229960000607 ziprasidone Drugs 0.000 description 1
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 1
- 229940039925 zyprexa Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461985381P | 2014-04-28 | 2014-04-28 | |
| US61/985,381 | 2014-04-28 | ||
| US201462047569P | 2014-09-08 | 2014-09-08 | |
| US62/047,569 | 2014-09-08 | ||
| PCT/US2015/027645 WO2015167968A1 (en) | 2014-04-28 | 2015-04-24 | Optically active pde10 inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2946754A1 CA2946754A1 (en) | 2015-11-05 |
| CA2946754C true CA2946754C (en) | 2022-08-30 |
Family
ID=54359189
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2946754A Active CA2946754C (en) | 2014-04-28 | 2015-04-24 | Optically active pde10 inhibitor |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US9493447B2 (OSRAM) |
| EP (1) | EP3137461B1 (OSRAM) |
| JP (1) | JP2017513913A (OSRAM) |
| KR (1) | KR102558505B1 (OSRAM) |
| CN (1) | CN106255690B (OSRAM) |
| AU (1) | AU2015253463B2 (OSRAM) |
| BR (1) | BR112016024523B1 (OSRAM) |
| CA (1) | CA2946754C (OSRAM) |
| ES (1) | ES2895487T3 (OSRAM) |
| IL (1) | IL248586B (OSRAM) |
| NZ (2) | NZ716462A (OSRAM) |
| RU (1) | RU2016146097A (OSRAM) |
| WO (1) | WO2015167968A1 (OSRAM) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2544679T3 (pl) * | 2010-03-12 | 2019-10-31 | Omeros Corp | Inhibitory PDE10 oraz powiązane kompozycje i sposoby |
| NZ716462A (en) * | 2014-04-28 | 2017-11-24 | Omeros Corp | Optically active pde10 inhibitor |
| NZ716494A (en) * | 2014-04-28 | 2017-07-28 | Omeros Corp | Processes and intermediates for the preparation of a pde10 inhibitor |
| US20160284909A1 (en) * | 2015-03-27 | 2016-09-29 | Gabriel Harley | Multi-diode solar cells |
| CA2980801A1 (en) * | 2015-04-24 | 2016-10-27 | Omeros Corporation | Pde10 inhibitors and related compositions and methods |
| US9920045B2 (en) | 2015-11-04 | 2018-03-20 | Omeros Corporation | Solid state forms of a PDE10 inhibitor |
Family Cites Families (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK178590D0 (da) | 1990-07-26 | 1990-07-26 | Novo Nordisk As | 1,4-disubstituerede piperaziner |
| PT100905A (pt) | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
| RU95113454A (ru) | 1992-12-02 | 1997-06-10 | Пфайзер Инк. (US) | Катехольные диэфиры как селективные ингибиторы фдэiv, фармацевтическая композиция, способы лечения |
| DE4323192A1 (de) | 1993-07-10 | 1995-01-12 | Basf Ag | Verfahren zur Herstellung von Homo- und Copolymerisaten von Alk-1-enen |
| DE4325846C1 (de) | 1993-07-31 | 1995-01-19 | Herberts Gmbh | Verwendung von Furan-modifizierten aromatischen Pinakolderivaten als Initiatoren und Furan-modifizierte aromatische Pinakolderivate als solche |
| DE4343286A1 (de) | 1993-12-17 | 1995-06-22 | Hoechst Ag | Heteroaromatische Verbindungen und ihre Verwendung in flüssigkristallinen Mischungen |
| DE4409501A1 (de) | 1994-03-19 | 1995-09-21 | Didier Werke Ag | Verschleißfutter eines Schachtofens und Stein hierfür |
| AU695230B2 (en) | 1994-06-24 | 1998-08-06 | Euro-Celtique S.A. | Compounds for and method of inhibiting phosphodiesterase IV |
| US5789434A (en) | 1994-11-15 | 1998-08-04 | Bayer Corporation | Derivatives of substituted 4-biarylbutyric acid as matrix metalloprotease inhibitors |
| TW332201B (en) | 1995-04-06 | 1998-05-21 | Janssen Pharmaceutica Nv | 1,3-Dihydro-1-(phenylalkyl)-2H-imidazol-2-one derivatives |
| TW424087B (en) | 1995-04-06 | 2001-03-01 | Janssen Pharmaceutica Nv | 1,3-dihydro-1-(phenylalkenyl)-2H-imidazol-2-one derivatives |
| US6037370A (en) | 1995-06-08 | 2000-03-14 | Vertex Pharmaceuticals Incorporated | Methods and compositions for stimulating neurite growth |
| EA199800650A1 (ru) | 1996-01-22 | 1999-02-25 | Фудзисава, Фармасьютикал Ко., Лтд | Новые соединения |
| AU4015497A (en) | 1996-08-26 | 1998-03-19 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Thiazole derivatives useful as selective inhibitors of pde-iv |
| JPH1087543A (ja) | 1996-09-17 | 1998-04-07 | Chisso Corp | アルコキシベンゼン誘導体、液晶組成物および液晶表示素子 |
| US6548490B1 (en) | 1997-10-28 | 2003-04-15 | Vivus, Inc. | Transmucosal administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction |
| WO1999045914A1 (en) | 1998-03-13 | 1999-09-16 | Maruho Kabushikikaisha | Alkyl amine derivative and local anesthetic agent using the same |
| GB9807354D0 (en) * | 1998-04-07 | 1998-06-03 | Glaxo Group Ltd | Antiviral compound |
| SE9804212D0 (sv) | 1998-12-04 | 1998-12-04 | Astra Pharma Prod | Compounds |
| WO2000034251A1 (en) | 1998-12-07 | 2000-06-15 | Smithkline Beecham Corporation | A method for quantitative determination of amino acids |
| SI1165516T1 (sl) | 1999-03-12 | 2005-02-28 | Boehringer Ingelheim Pharmaceuticals Inc. | Heterociklična sečnina in sorodne spojine, uporabne kot protivnetna sredstva |
| US7141593B1 (en) * | 1999-06-04 | 2006-11-28 | Abbott Laboratories | Pharmaceutical formulations |
| GB9929552D0 (en) | 1999-12-14 | 2000-02-09 | Proteus Molecular Design | Compounds |
| WO2001096334A2 (en) | 2000-06-15 | 2001-12-20 | Pharmacia Corporation | Heteroarylalkanoic acids as integrin receptor antagonists |
| US20030032579A1 (en) | 2001-04-20 | 2003-02-13 | Pfizer Inc. | Therapeutic use of selective PDE10 inhibitors |
| JP2004530703A (ja) * | 2001-05-22 | 2004-10-07 | ファイザー・プロダクツ・インク | 結晶形アジスロマイシン |
| US6821502B2 (en) * | 2002-06-12 | 2004-11-23 | Chevron U.S.A. Inc. | Method of making aluminum-containing zeolite with IFR structure |
| WO2004011410A1 (en) | 2002-07-27 | 2004-02-05 | Astrazeneca Ab | Chemical compounds |
| MXPA05003762A (es) | 2002-10-08 | 2005-07-22 | Scripps Research Inst | Inhibidores de hidrolasa de amida de acido graso. |
| WO2004041258A2 (fr) | 2002-10-30 | 2004-05-21 | Neuro3D | Utilisation d’inhibiteurs des phosphodiesterases des nucleotides cycliques, ayant une structure benzodiazepinique en therapie |
| TW200410921A (en) | 2002-11-25 | 2004-07-01 | Hoffmann La Roche | Mandelic acid derivatives |
| EP1568691A4 (en) | 2002-12-06 | 2010-08-25 | Kowa Co | ACCELERATOR FOR ERYTHROPOETIN PRODUCTION |
| MXPA05006727A (es) | 2002-12-20 | 2005-09-08 | Pharmacia Corp | Acidos heteroarilalcanoicos como antagonistas de receptor de integrina. |
| WO2004071509A1 (ja) | 2003-02-12 | 2004-08-26 | Nippon Chemiphar Co., Ltd. | オリゴデンドロサイト分化促進剤 |
| AU2004232973A1 (en) | 2003-04-18 | 2004-11-04 | Memory Pharmaceuticals Corporation | Pyrazole derivatives as phosphodiesterase 4 inhibitors |
| AR047541A1 (es) * | 2004-02-13 | 2006-01-25 | Sandoz Ag | Fosfato de 5-[[4-[2-metil-2-piridinil-amino-etoxi]fenil]metil]-2,4 tiazolidinadiona (rosiglitazona) y sus formas polimorficas |
| NZ550114A (en) | 2004-04-20 | 2011-02-25 | Transtech Pharma Inc | Substituted thiazole and pyrimidine derivatives as melanocortin receptor modulators |
| US20060074102A1 (en) | 2004-05-14 | 2006-04-06 | Kevin Cusack | Kinase inhibitors as therapeutic agents |
| US7351833B2 (en) * | 2004-07-23 | 2008-04-01 | Abbott Laboratories | (1S,5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate |
| US7449486B2 (en) | 2004-10-19 | 2008-11-11 | Array Biopharma Inc. | Mitotic kinesin inhibitors and methods of use thereof |
| US8436176B2 (en) * | 2004-12-30 | 2013-05-07 | Medicis Pharmaceutical Corporation | Process for preparing 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine |
| UA86283C2 (uk) | 2005-01-07 | 2009-04-10 | Пфайзер Продактс Инк. | Гетероароматичні сполуки хіноліну і їх застосування як інгібіторів pde10 |
| EP1850681B1 (en) | 2005-02-04 | 2019-12-18 | Firmenich Incorporated | Compounds comprising linked hetero aryl moieties and their use as novel umami flavor modifiers, tastants and taste enhancers for comestible compositions |
| US20060252807A1 (en) | 2005-04-22 | 2006-11-09 | Kalypsys, Inc. | Novel ortho-terphenyl inhibitors of p38 kinase and methods of treating inflammatory disorders |
| UA91546C2 (uk) * | 2005-05-03 | 2010-08-10 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | КРИСТАЛІЧНА ФОРМА 1-ХЛОР-4-(β-D-ГЛЮКОПІРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГІДРОФУРАН-3-ІЛОКСИ)-БЕНЗИЛ]-БЕНЗОЛУ, СПОСІБ ЇЇ ОДЕРЖАННЯ ТА ЇЇ ЗАСТОСУВАННЯ ПРИ ПРИГОТУВАННІ ЛІКАРСЬКИХ ЗАСОБІВ |
| MY152185A (en) * | 2005-06-10 | 2014-08-29 | Novartis Ag | Modified release 1-[(3-hydroxy-adamant-1-ylamino)-acetyl]-pyrrolidine-2(s)-carbonitrile formulation |
| EP1928848A2 (en) | 2005-08-04 | 2008-06-11 | Apogee Biothechnology Corporation | Sphingosine kinase inhibitors and methods of their use |
| KR20080050577A (ko) * | 2005-08-29 | 2008-06-09 | 사노피-아벤티스 유.에스. 엘엘씨 | 피리다지노[4,5-ｂ]인돌 유도체의 신규 결정질 형태 |
| US7642246B2 (en) * | 2005-09-13 | 2010-01-05 | Sicor Inc. | Pure rocuronium bromide |
| SI1954684T1 (sl) | 2005-11-15 | 2014-07-31 | Otsuka Pharmaceutical Co., Ltd. | Oksazolna spojina in farmacevtski sestavek |
| EP1968946A4 (en) | 2005-12-23 | 2010-05-05 | Astrazeneca Ab | IMIDAZOLE AS MODULATORS OF THE GABA B RECEPTOR |
| JP2009535394A (ja) | 2006-05-02 | 2009-10-01 | ファイザー・プロダクツ・インク | Ｐｄｅ１０阻害剤としての二環式ヘテロアリール化合物 |
| US20080090834A1 (en) | 2006-07-06 | 2008-04-17 | Pfizer Inc | Selective azole pde10a inhibitor compounds |
| US20080234345A1 (en) | 2006-09-08 | 2008-09-25 | Gene Logic Inc. | Method for reducing or alleviating inflammation in the digestive tract |
| SG185979A1 (en) | 2006-09-25 | 2012-12-28 | Ptc Therapeutics Inc | Crystalline forms of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]-benzoic acid |
| EP2079462A4 (en) * | 2006-09-28 | 2009-12-02 | Merck & Co Inc | PHARMACEUTICAL COMPOSITIONS OF HDAC INHIBITORS AND CHELABLE METAL COMPOUNDS AND METALO HDAC HEMMER CHELATE COMPLEXES |
| WO2008040669A2 (en) | 2006-10-02 | 2008-04-10 | Janssen Pharmaceutica N.V. | Novel intermediates for the preparation of a glyt1 inhibitor |
| US7837978B2 (en) * | 2006-10-13 | 2010-11-23 | Chevron U.S.A. Inc. | Process for preparing aluminum-containing molecular sieve SSZ-26 |
| US7786139B2 (en) | 2006-11-21 | 2010-08-31 | Omeros Corporation | PDE10 inhibitors and related compositions and methods |
| ES2624791T3 (es) | 2006-11-21 | 2017-07-17 | Omeros Corporation | Inhibidores de PDE10 y composiciones y métodos relacionados |
| PE20081506A1 (es) * | 2006-12-12 | 2008-12-09 | Infinity Discovery Inc | Formulaciones de ansamicina |
| WO2009008906A2 (en) | 2007-02-06 | 2009-01-15 | The Trustees Of The University Of Pennsylvania | Therapeutic compounds for blocking dna synthesis of pox viruses |
| AU2008253803A1 (en) * | 2007-05-22 | 2008-11-27 | Ultimorphix Technolgies B.V. | Tenofovir disoproxil hemi-fumaric acid Co-crystal |
| EP2017264A1 (de) | 2007-07-16 | 2009-01-21 | Bayer Cropscience Ag | Substituierte Phenylpropargylverbindungen, Verfahren zu deren Herstellung und deren Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| WO2009049022A1 (en) | 2007-10-10 | 2009-04-16 | Ore Pharmaceuticals Inc. | Method for treatment of pancreatitis |
| TW200944520A (en) * | 2008-01-29 | 2009-11-01 | Glaxo Group Ltd | Spiro compounds as NPY Y5 receptor antagonists |
| WO2009143178A2 (en) | 2008-05-20 | 2009-11-26 | Omeros Corporation | Pde10 inhibitors and related compositions and methods |
| TWI501965B (zh) | 2008-06-20 | 2015-10-01 | Lundbeck & Co As H | 作為ｐｄｅ１０ａ酵素抑制劑之新穎苯基咪唑衍生物 |
| US8377930B2 (en) | 2008-08-05 | 2013-02-19 | Omeros Corporation | PDE10 inhibitors and related compositions and methods |
| PL2544679T3 (pl) * | 2010-03-12 | 2019-10-31 | Omeros Corp | Inhibitory PDE10 oraz powiązane kompozycje i sposoby |
| NZ716462A (en) * | 2014-04-28 | 2017-11-24 | Omeros Corp | Optically active pde10 inhibitor |
| NZ716494A (en) * | 2014-04-28 | 2017-07-28 | Omeros Corp | Processes and intermediates for the preparation of a pde10 inhibitor |
-
2014
- 2014-09-10 NZ NZ716462A patent/NZ716462A/en unknown
- 2014-09-10 NZ NZ630803A patent/NZ630803A/en unknown
-
2015
- 2015-04-24 CN CN201580023106.6A patent/CN106255690B/zh active Active
- 2015-04-24 BR BR112016024523-7A patent/BR112016024523B1/pt active IP Right Grant
- 2015-04-24 JP JP2016564604A patent/JP2017513913A/ja active Pending
- 2015-04-24 WO PCT/US2015/027645 patent/WO2015167968A1/en not_active Ceased
- 2015-04-24 ES ES15785340T patent/ES2895487T3/es active Active
- 2015-04-24 EP EP15785340.9A patent/EP3137461B1/en active Active
- 2015-04-24 US US14/696,295 patent/US9493447B2/en active Active
- 2015-04-24 CA CA2946754A patent/CA2946754C/en active Active
- 2015-04-24 KR KR1020167031125A patent/KR102558505B1/ko active Active
- 2015-04-24 AU AU2015253463A patent/AU2015253463B2/en active Active
- 2015-04-24 RU RU2016146097A patent/RU2016146097A/ru not_active Application Discontinuation
-
2016
- 2016-10-12 US US15/291,948 patent/US9850238B2/en active Active
- 2016-10-27 IL IL248586A patent/IL248586B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| ES2895487T3 (es) | 2022-02-21 |
| IL248586B (en) | 2019-09-26 |
| US20170096420A1 (en) | 2017-04-06 |
| KR102558505B1 (ko) | 2023-07-21 |
| US9493447B2 (en) | 2016-11-15 |
| CN106255690A (zh) | 2016-12-21 |
| AU2015253463A1 (en) | 2016-11-03 |
| US9850238B2 (en) | 2017-12-26 |
| EP3137461B1 (en) | 2021-08-11 |
| BR112016024523B1 (pt) | 2022-10-11 |
| RU2016146097A (ru) | 2018-05-30 |
| CN106255690B (zh) | 2020-07-17 |
| KR20160141845A (ko) | 2016-12-09 |
| WO2015167968A1 (en) | 2015-11-05 |
| NZ630803A (en) | 2016-03-31 |
| NZ716462A (en) | 2017-11-24 |
| AU2015253463B2 (en) | 2018-12-06 |
| JP2017513913A (ja) | 2017-06-01 |
| IL248586A0 (en) | 2016-12-29 |
| BR112016024523A2 (pt) | 2017-08-15 |
| RU2016146097A3 (OSRAM) | 2018-11-15 |
| US20160024070A1 (en) | 2016-01-28 |
| EP3137461A1 (en) | 2017-03-08 |
| CA2946754A1 (en) | 2015-11-05 |
| EP3137461A4 (en) | 2017-09-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2946754C (en) | Optically active pde10 inhibitor | |
| TW495498B (en) | Amide derivative and a pharmaceutical composition containing the same as a Ca2+ release activated Ca2+ channel inhibitor | |
| CA2802216C (en) | Tetrahydrocarboline derivative and its use as an enpp2 inhibitor | |
| KR102093608B1 (ko) | 이미다조피리딘 화합물 | |
| JP5717445B2 (ja) | （ｓ）−エチル２−アミノ−３−（４−（２−アミノ−６−（（ｒ）−１−（４−クロロ−２−（３−メチル−１ｈ−ピラゾール−１−イル）フェニル）−２，２，２−トリフルオロエトキシ）−ピリミジン−４−イル）フェニル）プロパノエートの固体形態 | |
| CA2593515A1 (en) | Amino-imidazolones for the inhibition of beta-secretase | |
| JP2010500999A (ja) | ベータ−セクレターゼの阻害剤としてのイミダゾールアミン | |
| CA2870062A1 (en) | Pyrrolopyrazone inhibitors of tankyrase | |
| KR102688238B1 (ko) | 6, 7-디히드로 피라졸로[1, 5-a]피라지논 유도체 및 그 의약 용도 | |
| CN114685520B (zh) | 三并环化合物及其药物组合物和应用 | |
| US9650368B2 (en) | Processes and intermediates for the preparation of a PDE10 inhibitor | |
| HK1235766A1 (en) | Method of preparing an optically active pde10 inhibitor | |
| HK1235766B (en) | Method of preparing an optically active pde10 inhibitor | |
| JP2024532822A (ja) | ２－芳香族ヘテロ環置換含有ウレア化合物、その製造方法および使用 | |
| JP7035275B2 (ja) | ベンズイミダゾール化合物、及びアルツハイマー病又はハンチントン病の治療のためのその使用 | |
| EP2496570B1 (en) | Process for the preparation of 5-(2-amino-pyrimidin-4-yl)-2-aryl-1h-pyrrole-3-carboxamides | |
| JPWO2019044940A1 (ja) | 環状アミン誘導体及びその医薬用途 | |
| WO2020047360A1 (en) | Benzimidazole compounds and use thereof for treating alzheimer's disease or huntington's disease | |
| JP2021525792A6 (ja) | ベンズイミダゾール化合物、及びアルツハイマー病又はハンチントン病の治療のためのその使用 | |
| JPWO2019088057A1 (ja) | アニリド誘導体及びその医薬用途 | |
| WO2023187471A1 (en) | Heteroaryl derivative compounds, and uses thereof | |
| CA3222543A1 (en) | Use of substituted 5-(4-methyl-6-phenyl-4h-benzo[f]imidazo[1,5-a][1,4] diazepin-3-yl)-1,2,4-oxadiazoles in the treatment of inflammatory conditions | |
| JP2009529575A (ja) | キナーゼ阻害剤としてのピリジン−含有大複素環式化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20200420 |
|
| EEER | Examination request |
Effective date: 20200420 |