Substituted aminoalkylamide derivatives as antagonists of follicle stimulating hormone

A compound of the formula:

• wherein
• R1 and R2 are independently selected from the group consisting of hydrogen, C1-C6alkyl, C1-C6alkylcarbonyl, C1-C6perhaloalkyl, phenyl, phenyl C1-C6alkyl-, phenylcarbonyl-, pyridyl, pyridyl C1-C6alkyl-, pyridylcabonyl-, thienyl, thienyl C1-C6alkyl- and thienylcarbonyl, wherein the phenyl, pyridyl or thienyl is optionally substituted with one to three substituents independently selected from halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl, trifluoromethoxy or NO2;
• R3 is selected from the group consisting of hydrogen, C1-C6alkyl, C2-C4alkenyl and C2-C4alkynyl, where the C1-C6alkyl is optionally substituted with a phenyl, pyridyl, thienyl or furyl, wherein the phenyl, pyridyl, thienyl or furyl is optionally substituted with one to three substituents independently selected from halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl, trifluoromethoxy or NO2;
• R4 is selected from the group consisting of —C2-C6alkyl-, -cyclopentyl-, -cylcohexyl-, -cyclohexyl-CH2—, —CH2-cyclohexyl-CH2—, —CH2-phenyl-CH2—, —C(O)—CH2-phenyl-CH2—, —C(O)—C1-C6alkyl- and -cyclohexyl-CH2-cyclohexyl;
• where the R4 substituent is inserted into the compound of formula (I) from left to right, as defined;
• alternately, R2, R3, and R4 can be taken together with the two N atoms of the diamine portion of the molecule to form
• alternately, R3 can be taken together with R2 as —C2-C3alkyl-, provided that R4 is —C2-C6alkyl-;
• L is selected from the group consisting of —C3-C6cycloalkyl (wherein the cycloalkyl is substituted with R5 and R6), a bicyclic compound of the form
• (wherein the point of the attachment of the bicyclic compound is any carbon atom of the alkyl portion and wherein the aromatic portion of the bicyclic compound is optionally substituted with one to three substituents independently selected from halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl, trifluoromethoxy, NO2, acetamido, —NH2, —NH(C1-C6alkyl) or —N(C1-C6alkyl)2), and —(CH2)m—CR8R5R6;
• m is 0 to 3;
• R5 is selected from the group consisting of phenyl, naphthyl, (wherein the phenyl and naphthyl may be optionally substituted with one to three substituents independently selected from halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl, trifluoromethoxy, NO2, acetamido, —NH2, —NH(C1-C6alkyl), —N(C1-C6alkyl)2, C1-C6alkylcarbonylamino or C1-C6alkylsulfonylamino), bicyclo[4.2.0]octa-1,3,5-trienyl, 2,3-dihydro-1H-indolyl, N-methylpyrrolidinyl, 3,4-methylenedioxyphenyl, C3-C6cyloalkenyl, (wherein the cycloalkenyl group contains one or two double bonds), a six membered heteroaryl (wherein the six membered heteroaryl contains one to three N atoms), and a five membered heteroaryl (wherein the five membered heteroaryl contains one sulfur, oxygen or nitrogen, optionally contains one to three additional nitrogen atoms);
• wherein the point of attachment for the five or six membered heteroaryl is a carbon atom;
• and wherein the five or six membered heteroaryl is optionally substituted with one to three substituents independently selected from halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl, trifluoromethoxy or NO2;
• R6 is selected from the group consisting of hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkoxy, hydroxy and phenyl, (wherein the phenyl may be optionally substituted with one to three substituents independently selected from halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl or trifluoromethoxyl);
• provided that R6 may be phenyl only when R5 is phenyl;
• R8 is selected from the group consisting of hydrogen and C1-C6alkyl;
• Z is selected from the group consisting of —SO2—, —C(═O)—, and —C(═O)NH—;
• p is 0 to 1;
• is selected from the group consisting of phenyl and napthyl;
• X is selected from the group consisting of halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl, trifluoromethoxy, NO2, acetamido, —NH2, —NH (C1-C6alkyl) and —N(C1-C6alkyl)2;
• n is 0 to 3;
• Y is selected from the group consisting of phenyl, —O-phenyl, —NH-phenyl, naphthyl, (wherein the phenyl or naphthyl is optionally substituted with one to three substituents selected from halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl, trifluoromethoxy, NO2, cyano, methylthio, acetamido, formyl, -amino, -aminocarbonyl, —NH C1-C6alkyl, —N(C1-C6alkyl)2, —COOH, —COO(C1-C6alkyl), —COO(C1-C6alkylphenyl), C1-C6alkylcarbonylamino, C1-C6alkylaminocarbonyl, di(C1-C6alkyl)aminocarbonyl, aminosulfonyl, C1-C6akylaminosulfonyl or di(C1-C6alkyl)aminosulfonyl)), biphenyl, 3,4-methylenedioxyphenyl, dianthrenyl, dibenzothienyl, phenoxathiinyl, a six membered heteroaryl (wherein the six membered heteroaryl contains one to three nitrogen atoms), and a five membered heteroaryl (wherein the five membered heteroaryl contains one sulfur, oxygen or nitrogen atom, optionally contains one to three additional nitrogen atoms);
• wherein the point of attachment for the five or six membered heteroaryl is a carbon atom;
• and wherein the five or six membered heteroaryl is optionally substituted with one to three substituents selected from halogen, C1-C6alkyl, C1-C6alkoxy, trifluoromethyl, trifluoromethoxy, formyl, NO2, cyano, methylthio, acetamido, -amino, -aminocarbonyl, —NH C1-C6alkyl, —N(C1-C6alkyl)2, —COOH, —COO(C1-C6alkyl), or —COO(C1-C6alkylphenyl));
• q is 0 to 1;
• provided that when q is 1, n is 0;
• and stereoisomers and pharmaceutically acceptable salts or esters thereof.