Claims for Patent: 4,680,291

Summary for Patent: 4,680,291

Title:	Propenylamines, processes for their production and pharmaceutical compositions containing them
Abstract:	The present invention provides propenylamines useful as anti-mycotic agents.
Inventor(s):	Helmut Hamberger, Adrian Stephen, Anton Stutz, Peter Stutz
Assignee:	Novartis AG , Fidelity Union Bank
Application Number:	US06/934,772
Patent Claims:	1. A compound of formula I, ##STR79## wherein (a)(i) R1 is a radical of formula IIa, ##STR80## wherein R7 and R8, independently, are hydrogen, halogen of atomic number from 9 to 53, trifluoromethyl, hydroxy, nitro, lower alkyl or lower alkoxy,or a radical of formula IIb, IIc, IId, IIe, ##STR81## wherein R9 is hydrogen, halogen of atomic number from 9 to 53, hydroxy, lower alkyl or lower alkoxy, X is oxygen, sulphur, imino, lower alkylimino or a radical of formula --(CH2)r -- wherein r is 1, 2 or 3, s is 3, 4 or 5, and t is 2, 3 or 4, and R2 is hydrogen or lower alkyl, or (ii) R1 and R2 together with the carbon atom to which they are bound form a radical of formula IIf or IIg, ##STR82## wherein p is 1, 2 or 3,R3 and R5, independently, are hydrogen or lower alkyl,R4 is alkyl (C1-6), alkenyl (C3-12), alkynyl (C3-12) or cycloalkyl (C3-8)alkyl (C1-6); and R6 is (i) an aromatic, five-membered heterocycle containing one oxygen, sulphur or nitrogen hetero-ring atom and optionally an additional one or two nitrogen hetero-ring atoms and being optionally substituted on a carbon ring atom by halogen of atomic number from 9 to 53, hydroxy, lower alkyl or lower alkoxy, and any nitrogen ring atom present being optionally substituted when possible, by lower alkyl, (ii) a radical of formula IIIa, ##STR83## wherein R9 is as defined above, (iii) a radical of formula IIIb, --CO--R.sub.10 IIIb wherein R10 is alkyl (C1-12), alkenyl (C3-12), alkynyl (C3-12) cycloalkyl (C3-8)alkyl (C1-6), phenyl-alkyl (C7-12), phenyl, phenylalkoxy (C7-16), or aminoalkyl (C1-12); (iv) a radical of formula IIIc, IIId or IIIe, ##STR84## wherein R11, R12 and R13, independently, are hydrogen or lower alkyl,m is a whole number from 0 to 4, n is a whole number from 0 to 3, and v is a whole number from 0 to 5, (v) a radical of formula IIIf, ##STR85## wherein R14 is lower alkyl, alkoxy (C1-12)carbonyl, alkenyl (C3-12), alkynyl (C3-12), phenylalkyl (C7-12) or phenyl,R15 and R16, independently, are hydrogen or lower alkyl, and q is a whole number from 0 to 5, or (vi) a radical of formula IIIg ##STR86## wherein R17 and R18, independently, are hydrogen, halogen of atomic number from 9 to 53, trifluoromethyl, hydroxy, nitro, lower alkyl or lower alkoxy, with the general proviso that R1 is not a radical of formula IIa when R6 is a radical of formula IIIg or phenyl or phenylalkyl, (b)R1 is a radical of formula IIa to IIe, as defined above, R2, R5 and R6 are as defined above, and R3 and R4 together are --(CH2)u -- wherein u is a whole number from 1 to 8.or a chemotherapeutically acceptable salt thereof. 2. A pharmaceutical composition which comprises a therapeutically effective amount of a compound of claim 1, in association with a chemotherapeutically acceptable diluent or carrier. 3. A compound of claim 1, having the formula Ig, ##STR87## wherein R1 I is 1-naphthyl, optionally mono-substituted by lower alkyl or alkoxy,u is a whole number from 1 to 8, R6 II is of formula ##STR88## wherein R19 is hydrogen, hydroxy, lower alkoxy or lower alkyl, or of formula --CO--OR.sub.20 (e) whereinR20 is alkyl (C1-12) or phenylalkyl(C7-12) or of formula ##STR89## wherein m, n and v are as defined in claim 1. 4. A compound of claim 1, having the formula Ih, ##STR90## wherein R1 II is a radical of formula IIa, IIb wherein X is oxygen or sulphur, IIc, IId wherein s is 4, IIe wherein t is 3 or a radical of formula ##STR91## wherein R9 is as defined in claim 1,R2 and R are independently hydrogen or lower alkyl, u is a whole number from 1 to 8, R6 III is as defined in claim 1 for R6, with the following provisos,(a) R10 is other than phenyl or phenylalkoxy, and (b) when R1 II is 1-naphthyl optionally mono-substituted by lower alkyl or alkoxy and R2 and R5 are each hydrogen, R6 III is other than(i) a radical of formula IIIa, IIIb or IIIf, (ii) a radical of formula IIIc, IIId or IIIe, wherein R11, R12 and R13 are each hydrogen, or (iii) a radical of formula IIIg wherein one of R17 and R18 is hydrogen and the other is hydroxy, lower alkyl or lower alkoxy, or (iv) an optionally substituted thiophen or furan radical. 5. A compound of claim 1 having the formula Ii, ##STR92## wherein R1 III is a radical of formula IIa, IIb whereinX is oxygen or sulphur, IIc, IId wherein a is 4, IIe wherein t is 3, or a radical of formula ##STR93## R2, R3, R4, R5 and R9 are as defined in claim 1, with the proviso that R3 and R4 are other than --(CH2)u --, R6 IV is as defined in claim 1 for R6 with respect to formula I, with the following provisos(i) R10 is other than phenyl or phenylalkoxy and (ii) when R1 is a radical of formula IIa, R6 IV is other than a radical of formula IIIg, or phenyl. 6. A compound of claim 1, which is N-(3-cyclohex-1-en-1-yl-2-trans-propenyl)-N-methyl-N-(1-naphthylmethyl)amine. 7. A method of combatting mycoses in or on animals which comprises administering an anti-mycotic amount of a compound of claim 1 to an animal in need of such treatment. 8. The compound according to claim 1 which is 4-[N-methyl-N-(1-naphthylmethyl)]aminocrotonic acid ethyl ester. 9. The compound according to claim 1 which is N-(3-cyclohex-1-en-1-yl-2-cis-propenyl)-N-methyl-N-(1-naphthylmethyl)amine 10. The compound according to claim 1 which is N-(3-cyclohexyl-2-trans-propenyl)-N-methyl-N-(1-naphthylmethyl)amine. 11. The compound according to claim 1 which is N-methyl-N-[3-(5'-methyl-2'-thienyl)-2-trans-propenyl)-N-(1-naphthylmethyl)amine. 12. A compound according to claim 1 of the formula Ie: R.sub.1 --CH.sub.2 --N(CH.sub.3)--CH.sub.2 --CH═CHR.sub.6 Ie in which R1 and R6 are as defined in claim 1. 13. The compound of claim 12 in which R1 is 1-naphthyl and R6 is 2-thienyl. 14. The compound according to claim 12 in which R1 is 1-naphthyl and R6 is ##STR94## 15. The compound according to claim 12 in which R1 is 1-naphthyl and R6 is 4-pyridyl. 16. The compound according to claim 12 in which R1 is 1-naphthyl and R6 is --CH═CH.C6 H5. 17. The compound according to claim 12 in which R1 is 1-naphthyl and R6 is Cyclohept-1-en-1-yl. 18. The compound according to claim 12 in which R1 is 1-naphthyl and R6 is ##STR95## 19. The compound according to claim 12 in which R1 is 3-benzo[b]thienyl and R6 is Cyclohex-1-en-1-yl. 20. A compound according to claim 1 of the formula If: ##STR96## in which R1, R6 and u are as defined in claim 1. 21. The compound of claim 20 in which R1 is 1-naphthyl, R6 is C6 H5 and u is 4. 22. The compound of claim 20 in which R1 is 1-naphthyl, R6 is C6 H5 and u is 3. 23. The compound of claim 20 in which R1 is 1-naphthyl, R6 is C6 H5 and u is 5. 24. The compound of claim 20 in which R1 is 5-tetralinyl R6 is C6 H5 and u is 4. 25. The compound of claim 1 which is N-(3-cyclohex-1-en-1-yl-2-cis-propenyl)-2-(1'-naphthyl)-piperidine. 26. The compound of claim 1 which is N-(1-acenaphthenyl)-N-methyl-N-(3-phenyl-2-trans-propenyl)amine. 27. The compound of claim 1 which is N-(1-acenaphthenyl)N-methyl-N-[3-(5'-methyl-2'-thienyl)-2-trans-propenyl]amine. 28. The compound of claim 1 which is N-(6,7,8,8a-tetrahydro-1-acenaphthenyl)-N-methyl-N-(3-phenyl-2-transpropenyl)amine. 29. The compound of claim 1 which is N-methyl-N-(2,3-dihydro-1-phenalenyl)-N-(3-phenyl-2-trans-propenyl)amine. 30. A compound according to claim 1 in which R6 is an aromatic, five membered heterocycle as defined in claim 1. 31. A compound according to claim 1 in which R6 is a radical of formula IIIa. 32. A compound according to claim 1 in which R6 is a radical of formula IIIb. 33. A compound according to claim 1 in which R6 is a radical of the formula IIIc, IIId or IIIe. 34. A compound according to claim 1 in which R6 is a radical of the formula IIIf. 35. A compound according to claim 3 in which R14 is alkoxycarbonyl, alkenyl, alkynyl or phenylalkyl. 36. A compound according to claim 1 in which R3 and R4 together are --CH2)u wherein u is a whole number from 1 to 8; R1 is a radical of Formula IIa to IIe and R2, R5 and R6 are as defined in claim 1. 37. A compound according to claim 1 of the formula: ##STR97## wherein R1 is a radical of formula IIa, ##STR98## wherein R7 and R8, independently, are hydrogen, halogen of atomic number from 9 to 53, trifluoromethyl, hydroxy, nitro, lower alkyl or lower alkoxy, or a radical of formula IIb, IIc, IId, IIe, ##STR99## wherein R9 is hydrogen, halogen of atomic number from 9 to 53, hydroxy, lower alkyl or lower alkoxy,X is oxygen, sulphur, imino, lower alkylimino or a radical of formula --(CH2)r -- wherein r is 1, 2 or 3, s is 3, 4 or 5, and t is 2, 3 or 4, and R2 is hydrogen or lower alkyl, or R3 and R5, independently, are hydrogen or lower alkyl, R4 is alkyl (C1-6), alkenyl (C3-12), alkynyl (C3-12) or cycloalkyl (C3-8) alkyl(C1-6); and R6 is(i) an aromatic, five-membered heterocycle containing one oxygen, sulphur or nitrogen hetero-ring atom and optionally an additional one or two nitrogen hetero-ring atoms and being optionally substituted on a carbon ring atom by halogen of atomic number from 9 to 53, hydroxy, lower alkyl or lower alkoxy, and any nitrogen ring atom present being optionally substituted when possible, by lower alkyl, (ii) a radical of formula IIIa, ##STR100## wherein R9 is as defined above, (iii) a radical of formula IIIb, --CO--R.sub.10 IIb whereinR10 is alkyl (C1-12), alkenyl(C3-12), alkynyl (C3-12) cycloalkyl (C3-8)alkyl (C1-6), phenyl-alkyl (C7-12), phenyl, phenylalkoxy (C7-16), or aminoalkyl (C1-12);(iv) a radical of formula IIIc, IIId or IIIe, ##STR101## wherein R11, R12 and R13, independently, are hydrogen or lower alkyl, m is a whole number from 0 to 4, n is a whole number from 0 to 3, and v is a whole number from 0 to 5, or (v) a radical of formula IIIf, ##STR102## wherein R14 is lower alkyl, alkoxy (C1-12)carbonyl, alkenyl (C3-12), or alkynyl(C3-12), R15 and R16, independently, are hydrogen or lower alkyl, and q is a whole number from 0 to 5,or a chemotherapeutically acceptable salt thereof. 38. A compound according to claim 37 in which R1 is ##STR103## and R6 is ##STR104## where m, n, v, R7, R8, R11, R12 and R13 are as defined in claim 37. 39. A compound according to claim 37 in which R1 is ##STR105## and R6 is ##STR106## and q, R7, R8, R14, R15 and R16 are as defined in claim 37. 40. A compound according to claim 37 in which q is 0 or 1. 41. A compound according to claim 1 in which R1 is ##STR107## and s, t, X and R9 are as defined in claim 1. 42. A compound according to claim 1 in which R1 and R2 together with the carbon atom to which they are bound form a radical of formula IIf or IIg, ##STR108## wherein p is 1, 2 or 3.