1. An antenna, comprising a first conductor, a second conductor and a third conductor each of which has a certain length and does not intersect with each other,
wherein the third conductor is positioned between the first conductor and the second conductor, and an end of the first conductor electrically connects to an end of the second conductor, further connects to ground of radio frequency signal to form a connection point, an end of the third conductor which is adjacent to the connection point connects to a radio frequency signal line, and the length of the first conductor is greater than that of the second conductor.
2. The antenna according to claim 1, wherein the conductor is composed of an arrangement of a plurality of conductive materials.
3. The antenna according to claim 1, wherein the first conductor, the second conductor and the third conductor all extend in straight line, curve, spiral, or a combination of straight line and curve, in a same direction within a same plane.
4. The antenna according to claim 3, wherein the first conductor, the second conductor and the third conductor are provided on dielectric material(s), and the syntheses dielectric constant of the dielectric material(s) between the first conductor and the third conductor is greater than or equal to that between the second conductor and the third conductor.
5. The antenna according to claim 4, wherein geometry shape of the extension of the spiral is circle, curve, polygon or any combination shape of them, the extension of the combination of straight line and curve is any combination shape of straight line, curve and polygon, and a feeding point of the radio frequency signal is on end-points, which are in the central position of the extension of the spiral, of the conductors.
6. The antenna according to claim 4, wherein the identical first conductor, the identical second conductor and the identical third conductor are formed on the other side of the dielectric material(s) in the manner of mirror image, and the first conductors on both sides of the dielectric material(s) are connected by metallized through hole(s), the second conductors on both sides of the dielectric material(s) are connected by metallized through hole(s), and the third conductors on both sides of the dielectric material(s) are connected by metallized through hole(s).
7. The antenna according to claim 4 or 6, wherein a gap which has a certain length is carved on the dielectric material(s) between the first conductor and the third conductor andor between the second conductor and the third conductor.
8. The antenna according to claim 7, wherein dielectric material(s) with different dielectric constants are filled in the gap.
9. An antenna, comprising a first conductor and a second conductor each of which has a certain length and does not intersect with each other,
wherein an end of the first conductor forms a connection point connecting to ground of radio frequency signal, an end of the second conductor which is adjacent to the connection point connects to a radio frequency signal line, the first conductor and the second conductor extend in straight line, curve, spiral or a combination of straight line and curve in a same direction within a same plane.
10. The antenna according to claim 9, wherein the first conductor and the second conductor are provided on dielectric material(s), and geometry shape of the extension of the spiral is circle, curve, polygon or any combination shape of them, the extension of the combination of straight line and curve is the combination of straight line with circle, curve or polygon.
11. The antenna according to claim 9 or 10, wherein the conductor is composed of an arrangement of a plurality of conductive materials.
12. The antenna according to claim 9 or 10, wherein the identical first conductor and the identical second conductor are formed on the other side of the dielectric material(s) in the manner of mirror image, and the first conductors on both sides of the dielectric material(s) are connected by metallized through hole(s), the second conductors on both sides of the dielectric material(s) are connected by metallized through hole(s).
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A compound of structural Formula I
or a salt thereof, wherein:
R1\u2014R27 are independently selected from the group consisting of hydrogen and deuterium; and
at least one of R1\u2014R27 is deuterium.
2. The compound as recited in claim 1 wherein at least one of R1\u2014R27 independently has deuterium enrichment of no less than about 10%.
3. The compound as recited in claim 1 wherein at least one of R1\u2014R27 independently has deuterium enrichment of no less than about 50%.
4. The compound as recited in claim 1 wherein at least one of R1\u2014R27 independently has deuterium enrichment of no less than about 90%.
5. The compound as recited in claim 1 wherein at least one of R1\u2014R27 independently has deuterium enrichment of no less than about 98%.
6. The compound as recited in claim 1 wherein said compound has a structural formula selected from the group consisting of
7. The compound as recited in claim 1 wherein said compound has a structural formula selected from the group consisting of
8. The compound as recited in claim 7 wherein each position represented as D has deuterium enrichment of no less than about 10%.
9. The compound as recited in claim 7 wherein each position represented as D has deuterium enrichment of no less than about 50%.
10. The compound as recited in claim 7 wherein each position represented as D has deuterium enrichment of no less than about 90%.
11. The compound as recited in claim 7 wherein each position represented as D has deuterium enrichment of no less than about 98%.
12. The compound as recited in claim 7 wherein said compound has the structural formula:
13. The compound as recited in claim 7 wherein said compound has the structural formula:
14. The compound as recited in claim 7 wherein said compound has the structural formula:
15. A pharmaceutical composition comprising a compound as recited in claim 1 together with a pharmaceutically acceptable carrier.
16. A method of treatment of a dopamine receptor-mediated disorder comprising the administration of a therapeutically effective amount of a compound as recited in claim 1 to a patient in need thereof.
17. The method as recited in claim 16 wherein said disorder is selected from the group consisting of schizophrenia, anxiety, depression, and dysthymia.
18. The method as recited in claim 16 further comprising the administration of an additional therapeutic agent.
19. The method as recited in claim 18 wherein said additional therapeutic agent is selected from the group consisting of antipsychotics, antidepressants, and mood stabilizers.
20. The method as recited in claim 19 wherein said antidepressant is selected from the group consisting of citalopram, escitalopram, paroxetine, fluotexine, fluvoxamine, sertraline, isocarboxazid, moclobemide, phenelzine, tranylcypromine, amitriptyline, clomipramine, desipramine, dosulepin, imipramine, nortriptyline, protriptyline, trimipramine, lofepramine, maprotiline, amoxapine, mianserin, mirtazapine, duloxetine, nefazodone, reboxetine, trazodone, venlafaxine, tianeptine, and milnacipran.
21. The method as recited in claim 19 wherein said antipsychotic is selected from the group consisting of chlorpromazine, levomepromazine, promazine, acepromazine, triflupromazine, cyamemazine, chlorproethazine, dixyrazine, fluphenazine, perphenazine, prochlorperazine, thiopropazate, trifluoperazine, acetophenazine, thioproperazine, butaperazine, perazine, periciazine, thioridazine, mesoridazine, pipotiazine, haloperidol, trifluperidol, melperone, moperone, pipamperone, bromperidol, benperidol, droperidol, fluanisone, oxypertine, molindone, sertindole, ziprasidone, flupentixol, clopenthixol, chlorprothixene, thiothixene, zuclopenthixol, fluspirilene, pimozide, penfluridol, loxapine, clozapine, olanzapine, quetiapine, tetrabenazine, sulpiride, sultopride, tiapride, remoxipride, amisulpride, veralipride, levosulpiride, lithium, prothipendyl, risperidone, clotiapine, mosapramine, zotepine, pripiprazole, and paliperidone.
22. The method as recited in claim 19 wherein said mood stabilizer is selected from the group consisting of lithium carbonate, lamotrigine, lithium, sodium valproate, carbamazepine, triacetyluridine, and topiramate.
23. The method as recited in claim 16, further resulting in at least one effect selected from the group consisting of:
a. decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;
b. increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
c. decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
d. increased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound; and
e. an improved clinical effect during the treatment in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
24. The method as recited in claim 16, further resulting in at least two effects selected from the group consisting of:
a. decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;
b. increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
c. decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
d. increased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound; and
e. an improved clinical effect during the treatment in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
25. The method as recited in claim 16, wherein the method effects a decreased metabolism of the compound per dosage unit thereof by at least one polymorphically-expressed cytochrome P450 isoform in the subject, as compared to the corresponding non-isotopically enriched compound.
26. The method as recited in claim 25, wherein the cytochrome P450 isoform is selected from the group consisting of CYP2C8, CYP2C9, CYP2C19, and CYP2D6.
27. The method as recited claim 16, wherein said compound is characterized by decreased inhibition of at least one cytochrome P450 or monoamine oxidase isoform in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
28. The method as recited in claim 27, wherein said cytochrome P450 or monoamine oxidase isoform is selected from the group consisting of CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2G1, CYP2J2, CYP2R1, CYP2S1, CYP3A4, CYP3A5, CYP3A5P1, CYP3A5P2, CYP3A7, CYP4A11, CYP4B1, CYP4F2, CYP4F3, CYP4F8, CYP4F11, CYP4F12, CYP4\xd71, CYP4Z1, CYP5A1, CYP7A1, CYP7B1, CYP8A1, CYP8B1, CYP11A1, CYP11B1, CYP11B2, CYP17, CYP19, CYP21, CYP24, CYP26A1, CYP26B1, CYP27A1, CYP27B1, CYP39, CYP46, CYP51, MAOA, and MAOB.
29. The method as recited in claim 16, wherein the method reduces a deleterious change in a diagnostic hepatobiliary function endpoint, as compared to the corresponding non-isotopically enriched compound.
30. The method as recited in claim 29, wherein the diagnostic hepatobiliary function endpoint is selected from the group consisting of alanine aminotransferase (\u201cALT\u201d), serum glutamic-pyruvic transaminase (\u201cSGPT\u201d), aspartate aminotransferase (\u201cAST,\u201d \u201cSGOT\u201d), ALTAST ratios, serum aldolase, alkaline phosphatase (\u201cALP\u201d), ammonia levels, bilirubin, gamma-glutamyl transpeptidase (\u201cGGTP,\u201d \u201c\u03b3-GTP,\u201d \u201cGGT\u201d), leucine aminopeptidase (\u201cLAP\u201d), liver biopsy, liver ultrasonography, liver nuclear scan, 5\u2032-nucleotidase, and blood protein.
31. A compound as recited in claim 1 for use as a medicament.
32. A compound as recited in claim 1 for use in the manufacture of a medicament for the prevention or treatment of a disorder ameliorated by the modulation of dopamine receptor.