Claims
- 1. A compound of Formula II whereA is —O—R9; —S—X″; or —NR5X″; R1 is hydrogen, C1-C5 alkyl, —C(O)NR5X″, (C1-C4 alkylene)C(O)NR5X″, hydroxy substituted C1-C5 alkyl, C1-C5 acyl optionally substituted as the ethylene glycol ketal, C3-C6 cycloalkylcarbonyl, benzoyl, phenyl, phenyl(C1-C4 alkylene), phenoxyacetyl, phenylacetyl where the phenyl is optionally substituted with halo, C1-C4 alkyl, C1-C4 alkoxy, or trifluoromethyl, or α-hydroxy-α-benzoylbenzyl; R2 is hydrogen; or hydroxy substituted C1-C5 alkyl; R3′ is a structure selected from the group consisting of: R4 is phenethyl, or 2-arylethen-1-yl where aryl is furyl, pyrrolyl, pyridyl, thiazolyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, pyrimidinyl, thiadiazolyl, oxadiazolyl, quinolyl, isoquinolyl, naphthyl, or phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, nitro, halo, carboxy, and amido; R5 is hydrogen; hydroxy; C1-C4 alkoxycarbonyl; benzyl; or C1-C4 alkyl; X″ is C1-C4 alkylene ω-substituted with C1-C4 alkoxy, Y, (optionally substituted C1-C4 alkylene)-Y, or (optionally substituted C2-C4 alkylene)-NR7R8; Y is phenyl, optionally substituted phenyl, diphenylmethyl, C3-C6 cycloalkyl, naphthyl, tetrahydronaphthyl, indanyl, fluorenyl, pyrrolyl, 1-(C1-C4 alkyl)pyrrolyl, imidazolyl, pyrazolyl, pyridinyl, furyl, benzodioxanyl, tetrahydrofuryl, pyrrolidinyl, 1-(C1-C4 alkyl)pyrrolidinyl, 1-benzylpyrrolidinyl, piperidinyl, 1-benzylpiperidin-4-yl, or quinuclidinyl; R7 is hydrogen; or C1-C4 alkyl; R8 is C1-C4 alkyl, phenyl, or pyridinyl optionally substituted with nitro; R7 and R8 taken together with the nitrogen atom to which they are attached form morpholinyl, optionally substituted piperazinyl, or pyrrolidinyl; R5 and X″ taken together with the nitrogen to which they are attached form 2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl, piperidinyl optionally substituted at the 4-position with hydroxy, pyrrolidin-1-yl, piperidin-1-yl, benzyl, or piperidin-1-yl(C1-C4 alkylene), piperidinyl mono- or disubstituted with methyl, piperazinyl optionally substituted at the 4-position with C1-C4 alkyl, C3-C6 cycloalkyl, phenyl, phenyl(C1-C4 alkylene), α-methylbenzyl, N—(C1-C4 alkyl)acetamid-2-yl, or C1-C4 alkoxycarbonyl, 1,2,3,4-tetrahydroisoquinolin-2-yl, or homopiperazinyl substituted in the 4-position with C1-C4 alkyl; R9 is C1-C6 alkyl, (C2-C4 alkylene)trimethylsilyl, or benzyl where the phenyl ring of the benzyl moiety may be optionally substituted with 1 to 3 substituents independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, nitro, amino, cyano, hydroxy, or carboxamido; R11 is C1-C4 alkyl, C3-C7 cycloalkyl, phenyl optionally substituted with one or two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen, hydroxy, cyano, carbamoyl, amino, mono(C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, C1-C4 alkylsulfonylamino, and nitro, naphthyl optionally substituted with one or two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen, hydroxy, cyano, carbamoyl, amino, mono(C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, and nitro, or C1-C4 alkoxycarbonyl; R12 is C1-C4 alkyl optionally monosubstituted with a substituent selected from the group consisting of hydroxy, protected carboxy, carbamoyl, thiobenzyl and C1-C4 thioalkyl, phenyl optionally substituted with one or two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen, hydroxy, cyano, carbamoyl, amino, mono(C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, C1-C4 alkylsulfonylamino, and nitro, naphthyl optionally substituted with one or two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen, hydroxy, cyano, carbamoyl, amino, mono(C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, and nitro; or C1-C4 alkoxycarbonyl; R13 is C1-C4 alkoxycarbonyl, benzyloxycarbonyl where the phenyl group is optionally substituted with one or two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen, cyano, nitro, amino, carbamoyl, hydroxy, mono(C1-C4 alkyl)amino, and di(C1-C4 alkyl)amino, benzoyl where the phenyl group is optionally substituted with one or two substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen, hydroxy, cyano, carbamoyl, amino, mono(C1-C4 alkyl)amino, di(C1-C4 alkyl)amino, C1-C4 alkylsulfonylamino, and nitro; and R14 and R15 are C1-C5 alkanoyloxy, benzoyloxy optionally substituted with one or two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen, cyano, nitro, amino and C1-C4 alkoxycarbonyl, benzyloxy, diphenylmethoxy, or triphenylmethoxy; or one of R14 and R15 is hydrogen and the other is C1-C5 alkanoyloxy, benzoyloxy optionally substituted with one or two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen, cyano, nitro, amino and C1-C4 alkoxycarbonyl, benzyloxy, diphenylmethoxy, or triphenylmethoxy; providing that: a) R2 may be other than hydrogen only when R1 is hydroxy substituted C1-C5 alkyl; and b) when A is —OR9, R1 must be selected from the group consisting of —C(O)NR5X″, (C1-C4 alkylene)C(O)NR5X″, and 2,2-dimethylpropanoyl; and solvates and pharmaceutically acceptable acid addition salts thereof.
- 2. A compound of claim 1 where A is —NR5X″.
- 3. A compound of claim 2 were R2 is hydrogen.
- 4. A compound of claim 3 where R1 is C1-C5 alkyl, hydroxy substituted C1-C5 alkyl, or C1-C5 acyl optionally substituted as the ethylene glycol ketal.
- 5. A compound of claim 1 where X″ is Y; (optionally substituted C1-C4 alkylene)-Y; or (optionally substituted C2-C4 alkylene)-NR7R8.
- 6. A compound of claim 5 where Y is optionally substituted phenyl.
- 7. A pharmaceutical composition which comprises, in association with a pharmaceutically acceptable carrier, diluent or excipient, a compound of claim 1.
Priority Claims (3)
Number |
Date |
Country |
Kind |
9605044 |
Mar 1996 |
GB |
|
9605045 |
Mar 1996 |
GB |
|
9605046 |
Mar 1996 |
GB |
|
Parent Case Info
This application is a divisional of, and claims the benefit of priority of, U.S. application Ser. No. 09/733,430, filed Dec. 8, 2000, now U.S. Pat. No. 6,521,611, filed on Feb. 18, 1997, which is a divisional application 09/125,737 of U.S. Pat. No. 6,204,260, filed on Aug. 19, 1999, issued on Mar. 30, 2001, which is a 371 of PCT/US97/03039, filed Feb. 20, 1997, and claims the benefits of provisional application Ser. Nos. 60/012,149, 60/012,188 and 60/012,215 all filed on Feb. 23, 1996, the contents of each of which are herein incorporated by reference in their entirety.
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Provisional Applications (3)
|
Number |
Date |
Country |
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60/012149 |
Feb 1996 |
US |
|
60/012188 |
Feb 1996 |
US |
|
60/012215 |
Feb 1996 |
US |