.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 7,902,366

« Back to Dashboard

Details for Patent: 7,902,366

Title:NK.sub.1 antagonists
Abstract: A NK.sub.1 antagonist having the formula (I), ##STR00001## wherein Ar.sup.1 and Ar.sup.2 are optionally substituted phenyl or heteroaryl, X.sup.1 is an ether, thio or imino linkage, R.sup.4 and R.sup.5 are not both H or alkyl, and the remaining variables are as defined in the specification, useful for treating a number of disorders, including emesis, depression, anxiety and cough. Pharmaceutical compositions. Methods of treatment and combinations with other agents are also disclosed.
Inventor(s): Paliwal; Sunil (Monroe Township, NJ), Reichard; Gregory A. (Ann Arbor, MI), Wang; Cheng (Summit, NJ), Xiao; Dong (Warren, NJ), Tsui; Hon-Chung (East Brunswick, NJ), Shih; Neng-Yang (Warren, NJ), Arredondo; Juan D. (Montclair, NJ), Wrobleski; Michelle Laci (Whitehouse Station, NJ), Palani; Anandan (Bridgewater, NJ)
Assignee: OPKO Health, Inc. (Miami, FL)
Filing Date:Feb 21, 2006
Application Number:11/358,827
Claims:1. A compound having the formula (I): ##STR00253## or a pharmaceutically acceptable salt thereof, wherein Ar.sup.1 is phenyl, wherein said phenyl can be unsubstituted or substituted with 1 to 3 fluoro; Ar.sup.2 is bis(trifluoromethyl)phenyl; X.sup.1 is --O--; R.sup.1 and R.sup.2 are independently selected from the group consisting of H, C.sub.1-C.sub.6 alkyl or hydroxyl (C.sub.1-C.sub.3alkyl), providing that at least one of R.sup.1 and R.sup.2 is H; R.sup.3 is H; R.sup.6 and R.sup.7 are each H; n.sub.2 is 2; R.sup.4 and R.sup.5 are each independently selected from the group consisting of --(CR.sup.28R.sup.29).sub.n1-G, where, n.sub.1 is 0-5; and G is H, --NR.sup.13R.sup.14, --NR.sup.12C(O)R.sup.14, --C(O)NR.sup.13R.sup.14, --OC(O)NR.sup.13R.sup.14, NR.sup.12C(O)OR.sup.13, --NR.sup.12(C(O)NR.sup.13R.sup.14), --NR.sup.12S).sub.2R.sup.13, R.sup.19-heteroaryl, R.sup.19-aryl, wherein heteroaryl is selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, furanyl, benzofuranyl, thienyl, benzothienyl, thiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazoyl, tetrazolyl, isothiazolyl, benzothiazolyl, benzoxazolyl, oxazolyl, pyrrolyl, isoxazolyl, 1,3,5-triazinyl or indolyl and aryl is selected from phenyl, --OH, --O(C.sub.1-C.sub.6alkyl), --C(OR.sup.12)(R.sup.13)(R.sup.14), --OC(O)R.sup.14, ----C(O)R.sup.13, heterocycloalkenyl optionally substituted by 1 substituent independently selected from the group consisting of R.sup.30 and R.sup.31, ##STR00254## provided that R.sup.4 and R.sup.5 are not both selected from the group consisting of H, alkyl and cycloalkyl; further provided that, when one of R.sup.4 and R.sup.5 is --OH, then the other one of R.sup.4 and R.sup.5 is not alkyl or (R.sup.19aryl); R.sup.12 is H, C.sub.1-C.sub.6 alkyl or C.sub.3-C.sub.8 cycloalkyl; R.sup.13 and R.sup.14 are reach independently selected from the group consisting of H, C.sub.1-C.sub.6alkyl, --CH.sub.2CF.sub.3, C.sub.3-C.sub.6 cycloalkyl, (C.sub.3-C.sub.8)cycloalkyl(C.sub.1-C.sub.6)alkyl, phenyl or pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, furanyl, benzofuranyl, thienyl, benzothienyl, thiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazoyl, tetrazolyl, isothiazolyl, benzothiazolyl, benzoxazolyl, oxazolyl, pyrrolyl, isoxazolyl, 1,3,5-triazinyl or indolyl; or R.sup.13 and R.sup.14, together with the nitrogen atom to which they are both attached, form a 5- to 6-membered saturated or unsaturated ring that is optionally substituted with --OR.sup.12, where one of the carbon atoms in the ring is optionally replaced by a heteroatom selected from --O--; n.sub.6 is 0, 1 or 2; R.sup.18 is H; each R.sup.19 is a substituent on the aryl or heteroaryl ring to which it is attached and is independently selected from the group consisting of H or C.sub.1-C.sub.6 alkyl; R.sup.23 and R.sup.24 are each independently selected from the group consisting of H and C.sub.1-C.sub.6 alkyl; or R.sup.23 and R.sup.24, together with the carbon atom to which they are both attached, form a C.dbd.O or cyclopropyl group; R.sup.27 is H, --OH or C.sub.1-C.sub.6 alkyl; R.sup.28 and R.sup.29 are each independently selected from the group consisting of H and C.sub.1-C.sub.2alkyl; R.sup.30 and R.sup.31 are each independently selected from the group consisting of H, --OH, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.8 cycloalkyl, (C.sub.3-C.sub.8)cycloalkyl(C.sub.1-C.sub.6)alkyl and --C(0)NR.sup.13R.sup.14; or R.sup.30 and R.sup.31, together with the carbon atom to which they are both attached, form .dbd.O, .dbd.S, a cyclopropyl ring or .dbd.NR.sup.36; R.sup.32 and R.sup.33 are each H; R.sup.34 is H, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.8 cycloalkyl, (C.sub.3-C.sub.8)cycloalkyl(C.sub.1-C.sub.6)alkyl or hydroxyl(C.sub.2-C.sub.6)alkyl; R.sup.35 is H, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.8 cycloalkyl, (C.sub.3-C.sub.8)cycloalkyl(C.sub.1-C.sub.6)alkyl, -P(0)(OH).sub.2, allyl, hydroxyl(C.sub.2-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, --SO.sub.2R.sup.15 or --(CH.sub.2).sub.2--N(R.sup.12)--SO.sub.2--R.sup.15; R.sup.36 is H, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.8 cycloalkyl, (C.sub.3-C.sub.8)cycloalkyl(C.sub.1-C.sub.6)alkyl, --NO.sub.2, --CN or OR.sup.12; R.sup.37 is 1 to 3 substituents independently selected from the group consisting of H, C.sub.1-C.sub.6 alkyl, --OH, C.sub.1-C.sub.6 alkoxy and halogen; r is 1to 3; X.sup.2 is --NR.sup.35--, --O--, --S--, --S(O)--, --S(O.sub.2--, --CH.sub.2--, --CF.sub.2-- or --CR.sup.12F--; X.sup.3 is --NR.sup.34--, --N(CONR.sup.13R.sup.14)--, --N(CO.sub.2R.sup.15)--, --N(COR.sup.12)--, --N(SO.sub.2NHR.sup.13)--, --O--, --S--, --S(O)--, SO.sub.2--, --CH.sub.2--, --CF.sub.2--, or CR.sup.12F--; n.sub.3 is 1 to 5; and n.sub.5 is 1 to 3; or a diastereomer, enantiomer, stereoisomer, regiostereomer, rotomer, or tautomer thereof.

2. The compound or salt according to claim 1 wherein R.sup.4 is --NR.sup.13R.sup.14, --NR.sup.12C(O)R.sup.14, NR.sup.12C(O)OR.sup.13, NR.sup.12(C(O)NR.sup.13R.sup.14, --OH, --O--(C.sub.1-C.sub.6)alkyl, --O--(C.sub.3-C.sub.8cycloalkyl, --OC(O)R.sup.14, --OC(O)NR.sup.13R.sup.14, --NR --SO.sub.2NR.sup.13R.sup.14, R.sup.19-heteroaryl, ##STR00255## wherein X.sub.2 is --O--, --S--, --CH.sub.2-- or --NR.sup.35; and R.sup.5 is --C(O)OR.sup.13 or --C(O)NR.sup.13R.sup.14.

3. The compound or salt according to claim 2 where R12 and R27 are independently selected from the group consisting of H and --CH3; n3 is 2 or 3; and n5 is 1 or 2.

4. the compound or salt according to claim 2, wherein R12 and R27 are H; n3 is 2 or 3; and n5 is 1 or 2.

5. A compound having the following structure: ##STR00256## and pharmaceutically acceptable salts thereof.

6. A compound having the following structure: ##STR00257## and pharmaceutically acceptable salts thereof.

7. A compound having the following structure: ##STR00258## and pharmaceutically acceptable salts thereof.

8. The compound or salt according to claim 1, wherein the compound is: ##STR00259##

9. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 in a pharmaceutically acceptable carrier.

10. The pharmaceutical composition according to claim 9, further comprising at least one serotonin reuptake inhibitor.

11. The pharmaceutical composition according to claim 9, further comprising at least one serotonin 5-HT3 receptor antagonist, or at least one corticosteroid or at least one substituted benzamide.

12. The pharmaceutical composition according to claim 9, further comprising at least one serotonin 5-HT3 receptor antagonist and at least one corticoid steroid.

13. The pharmaceutical composition according to claim 9, further comprising at least one substituted benzamide and at least one corticosteroid.

14. The pharmaceutical composition according to claim 10, where the selective serotonin reuptake inhibitor is fluoxetine, fluvoxamine, paroxetine, sertraline, or a pharmaceuticall acceptable salt thereof.

15. The pharmaceutical composition according to claim 11, where the serotonin 5-HT3 receptor antagonist is ondansetron, dolasetron, palonsetron or granisetron, the corticosteroid is dexamethasone, and the substituted benzamide is metoclopramide.

16. The pharmaceutical composition according to claim 12 where the serotonin 5-HT3 receptor antagonist is ondansetron, dolasetron, palosetron or granisetron, the corticosteroid is dexamethasone.

17. The pharmaceutical composition according to claim 11, wherein the corticosteroid is dexamethasone, and the substituted benzamide is metoclopramide.

18. The pharmaceutical composition according to claim 13, where the corticosteroid is dexamethasone and the substituted benzamide is metoclopramide.

19. A compound selected from the group consisting of: ##STR00260## ##STR00261## ##STR00262## ##STR00263## ##STR00264## ##STR00265## ##STR00266## ##STR00267## ##STR00268## ##STR00269## ##STR00270## ##STR00271## ##STR00272## ##STR00273## and pharmaceutically acceptable salts thereof.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc