MXPA96005355A

MXPA96005355A - The use of nk-1 receptor antagonists to prepare compositions to treat can

Info

Publication number: MXPA96005355A
Application number: MXPA/A/1996/005355A
Authority: MX
Inventors: R Howard Harry
Original assignee: Pfizer Inc
Priority date: 1995-11-06
Filing date: 1996-11-04
Publication date: 1998-07-03

Abstract

The present invention relates to the use of certain NK-1 receptor antagonists (eg Substance P receptor antagonists) for treating cancer patients, in particular to patients suffering from a small cell lung carcinoma, APUDoma, astrocytoma, neuroendocrine tumor or extrapulmonary small cell carcinoma

Description

THE USE OF NK-1 RECEPTOR ANTAGONISTS TO PREPARE COMPOSITIONS TO TREAT C NCER The present invention relates to the use of certain NK-1 receptor antagonists (including certain substance P receptor antagonists) to treat cancer patients suffering from small cell lung carcinoma, APUDorna, astrocytoma, neuroendocrine tumor or extrapulmonary small cell carcinoma. Ant l Oroez, et al., International Journal of Cancer, 1995, 6J3, 82-87, describes the use of a series of peptide antagonists of substance P to inhibit the proliferation of small cell lung carcinoma (for example in the cell line designated HCI-h69). Paul Bunn et al. , Caneer Research, 1994, 5_4, 3602-3610, describes A further series of substance P antagonists that are also peptidic and that are capable of inhibiting in vitro growth in a number of small cell lung carcinoma cell lines (for example, the so-called NCI-H510, NCI-H345 and SHP-77).

SUMMARY OF THE INVENTION This invention relates to a method for treating cancer in a mammal, including a human, which comprises administering to said mammal a therapeutically effective amount of an NK-1 receptor antagonist selected from the compounds described below. "Cancer treatment" as used herein, refers to inhibiting or controlling the proliferation of small cell lung carcinoma, APUDoma, neuroendocrine tumor, extrapulmonary small cell carcinoma, or astrocytoma. An "effective tertiary amount" as used herein, refers to an effective amount to treat cancer, as defined above. An "astrocytoma" is a tumor composed of astrocytes. Astrocytes are neurogliales cells of ectodermal origin, characterized by fibrous, protoplasmic or plasma-fibrous processes. The APUDomas are tumors formed by APUD cells (Amine Precursor Uptake and Decarboxylation). APUD cells are diffused throughout the body (for example, in the chromaffin system, the hypothalamus or pituitary gland, the thyroid, parathyroid, lung, gastrointestinal tract, and pancreas) and are apparently unrelated although they share certain cytochemical and ultrastructural features. . They synthesize structurally related peptides (usually biogenic amine) that function as hormones or neurotransmitters (for example epinephrine, norepinephrine, dopamine, serotonin, enkephalin, somatostatin, neurotensin and substance P). The ADUP cells concentrate the amino acid precursors of these amines and deecarboxylate them in their respective amines.

More specifically, this invention relates to a method of treating cancer in a mammal, including a human, which comprises administering to said mammal a therapeutically effective amount of an NK-1 receptor antagonist which is a compound of formula in which A is a ring system selected from phenyl, naphthyl, thienyl, dihydroquinolinyl, quinolinyl and indolyl, and wherein the side chain containing NR2R3 is attached to a carbon atom of the ring system A; AA is an aryl group selected from phenyl, naphthyl, thienyl, quinolinyl, dihydroquinoline and indolinyl, and wherein the side chain containing NR2R3 is attached to a carbon atom of AA; AAA is an aryl group selected from phenyl, naphthyl, thienyl, dihydroquinolino, quinolinyl and indolinyl, and wherein the side chain --CH2PR3 is attached to a carbon atom of the AAA ring; P is NR2, 0 S, SO or S02; 0 is SO2, NH, -N (Ci-Ce alkyl) or (C6-C6 alkyl) -N-S02 wherein the point of attachment of the aforementioned (Ci-Ce alkyl) -N-SO2 to the AAA ring is the nitrogen atom and the binding point of? ¡> it is the sulfur atom; ) i and U2 are independently selected from hydrogen, halo or an alkyl (Ci-Cß), S- (Ci-C3 alkyl) and alkoxy (Ci-Cß) optionally substituted with one to three fluorine atoms; Ul is hydrogen, an alkyl (Ci-Cß) optionally substituted with from one to three fluorine atoms, -S (0) v "alkyl (Ci-Cß) wherein v is zero, one or two, halo or an alkoxy (Ci-Ce) optionally substituted with one to three fluorine atom: i is hydrogen, a (C 1 -C 10) alkoxy optionally substituted with one to three fluorine atoms or an alkyl (Ci-Cyano) optionally substituted with from one to three fluorine atoms; γ2 and γ3 are independently selected from hydrogen, halo, nitro, a (C1-C10) alkyl optionally substituted with one to three fluorine atoms, an alkoxy (Ci-Cyano) optionally substituted with one to three fluorine, hydroxyl, phenyl, cyano, amino, an alkylamino (Ci-Cß), a dialkylamino (Ci-Cß), -CÍO) -NH ~ alkyl (Ci-Cß), (Ci-Ce alkyl) - C (0) ~ NH-alkyl (Ci-Cß), hydroxyalkyl (C 1 -C 4), alkoxy (C 1 -C 4) -alkyl (C 1 -C 4), -NHC (0) H and -NHC (O) -alkyl ( C? ~ C6); X5 is a four to six member heterocyclic ring containing one to three heteroatoms selected from sulfur, nitrogen and oxygen (eg, thiazolyl, pyrrolyl, thienyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, thiadiazolyl or imidazolyl), wherein said heterocyclic ring may be optionally substituted with one to three substituents, preferably from none to two substituents, independently selected from phenyl, an alkyl (Ci-Cß) optionally substituted by one to three fluorine atom, an alkoxy (Ci-Cd) optionally substituted with one to three fluorine atoms and halo; R is a heterocyclic ring selected from oxygen, sulfur and nitrogen (for example, thiazolyl, azetidinyl, pyrrolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, isothiazolyl, imidazolyl, isoxazolyl or oxazolyl), wherein said heterocyclic ring may contain from none to three double bonds and may be optionally substituted with one or more substituents, preferably one or two substituents, independently selected from an alkyl (Ci-Cg) optionally substituted with one to three fluorine atoms and an alkoxy (Ci-Ce) optionally substituted with one to three fluorine atoms; RI is selected from amino, alkylamino (Ci-Cß), dialkylamino (Ci-Cs) -S (0) v ~ phenyl in which v is zero, one or two, ~ S (0) v ~ benzyl, wherein v is zero, one or two, -0-phenyl, -0-benzyl, -S02 R6R5 in which of R < and RS each is, independently, an alkyl (Ci-Cfi), or R * and S, together with the nitrogen to which they are attached, forms a saturated ring containing a nitrogen and from three to six carbons, -NHC (0) -alkyl? (Ct-Cs), -NHC (0) CF3, (Ci-Cio alkyl) -N-SO2- (C1-C0 alkyl) wherein one or both of the alkyl radicals may be optionally substituted with one to three atoms of fluorine, ~ N (SO 2 - C 1 -C 0 alkyl) 2.

(C1-C10 alkyl) --N-SO2 - phenyl and (C 1 -C 10 alkyl) -N-SO 2 -benzyl; and wherein any of the phenyl radicals of the above R groups can be optionally substituted with one to three substituents independently selected from a (C 1 -C 4) alkyl, a (C 1 -C 4) alkoxy and halo; or Ri is a group that has the formula wherein a is 0, 1 or 2 and the asterisk represents a bond in a meta position with respect to the side chain R R3 CH2; dotted lines of formula Ib represent that one of the links X-Y and Y-Z may optionally be a double link; X is selected from = CH-, -CH2-, -0-, -S-, -SO-, - SO2-, -N (R *) - -NH-, = N-, -CHCalkyl (Ci-C * )] -, = CCalkyl (C? -C6)] ~, ~ CH (C6H5) ~ y = C (C6Hs) -; Y is selected from CO, C = NR *, C = S, = CH-, -CH2-, = CCalkyl (C? -C6)] -, -CHCalkyl (Ci-Cß)] -, -CHICßHs) -, = N-, -NH-, -N (R *) -, = C (hal?) -, ^ C (0R *) -, = C (SR *) -. = C (NR *) ~, -0-, -S- and SO2 in which the phenyl radicals of the and -CHICßHs) - mentioned may be optionally substituted with one to three substituents independently selected from trifluoromethyl and halo, and wherein the alkyl radicals of the -CCalkyl (Ci-Cß)] - and -CHCalkyl (Ci-Cß)] - and -CHCalkyl (Ci-Cß)] - may be optionally substituted with one to three fluorine atoms; Z is selected from -CU-, -CH2-, = N-, -NH-, -S-, -N (R *) -, = C (C6Hs) -, -CH (C6Hs) ~, - "CCalkyl ( C? -C6) 3- and -CHCalkyl (Ci-Cß)! -; or X, Y and Z, together with the two carbon atoms shared between the benzo ring and the XYZ ring, form a fused pyridine or pyrimidine ring R * is an alkyl (Ci-Cß) or phenyl, and each occurrence of R * is independent of other occurrences of R * in the same molecule, R2 is hydrogen or a -C? 2alkyl (C1-C10); select between I V IX HIV wherein Rβ and Rio are independently selected from fuyl, thienyl, pyridyl, indolyl, biphenyl and phenyl, wherein said phenyl may be optionally substituted with one or two substituents independently selected from halo, (C 1 -C 10) alkyl optionally substituted with one to three fluorine atoms, an optionally substituted (C 1 -C 6) alkoxy having one to three fluorine, carboxyl, benzyloxycarbonyl and (C 1 -C 3) alkoxycarbonyl atoms; R7 is selected from branched (C3-C.I) alkyls, branched (Cs-Cg) alkenyls, (C5-C7) cycloalkyls and the radicals mentioned in the definition of R &; R8 is hydrogen or an alkyl (Ci-Cß); R9 and R! ° are independently selected from phenyl, biphenyl, naphthyl, pyridyl, benzhydryl, thienyl and furyl, and R9 and I9 may be optionally substituted with one to three substituents independently selected from halo, an alkyl ( C1-C10) optionally substituted with one to three fluorine atoms and one (C 1 -Cy) alkoxy optionally substituted with one to three fluorine atoms; ? i is (CH2)? where 1 is an integer from one to three, or Y is a group of formula 3 Z is oxygen, sulfur, amino, alkylamino (C? ~ C3) or (CH2)? where k is zero, one or two; x is an integer from zero to four; and is an integer from zero to four; z is an integer from one to six, in which the ring containing (CH2) z can contain from zero to three double bonds and one of the carbons of (CH2)? it may be optionally replaced by oxygen, sulfur or nitrogen; or it is two or three; p is zero or one; r is one, two or three; R 1 is thienyl, biphenyl or phenyl optionally substituted with one or two substituents independently selected from halo, an alkyl (Ci-Cio) optionally substituted with one to three fluorine atoms and an optionally substituted (Ci- C? O) alkoxy with one to three fluorine atoms; X * is (CH2) in which q is an integer from 1 to 6 and in which any of the simple carbon-carbon bonds of said (CH2) q may optionally be replaced by a carbon-carbon double bond and in which any of the carbon atoms of said (CH2) q may be optionally substituted with Ri * and wherein any of the carbon atoms of said (CH2) q may be optionally substituted with RiS; rn is an integer from 0 to 8, and any of the simple carbon-carbon bonds of (CH2) m and in which both carbon atoms of such a bond are linked together, and to another carbon atom of the chain (CH2) m, may optionally be replaced by a carbon-carbon double bond or a carbon-carbon triple bond, and wherein any of the said carbon atoms (CH2) »» having the required binding sites required may be optionally substituted with Rl7; R12 is a radical selected from hydrogen, a straight or branched (Ci-Cß) alkyl, a (C3-C7) cycloalkyl, wherein one of the carbon atoms may be optionally replaced by nitrogen, oxygen or sulfur; an aryl selected from biphenyl, phenyl, indanyl and naphthyl, a heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; (C2-C6) alkyl phenyl, benzhydryl and benzyl, wherein the point of attachment in Ri is a carbon atom unless R12 is hydrogen, and wherein each of the aforementioned aryl and heteroaryl groups and the phenyl radicals of said benzyl, alkyl (C2-C6) alkyl and benzhydryl mentioned may be optionally substituted with one or more substituents independently selected from halo, nitro, a (C1-C10) alkyl optionally substituted by one to three fluorine atoms, an alkoxy (C1-C10) optionally substituted with one to three fluorine, ammonium, hydroxyalkyl (Ci-Cß), alkoxy atoms. (Ci-Cß), alkyl (Ci-Ce), alkylamino (Ci-Cß), (Ci-C-alkyl) -0-C (0) -, (Ci-C-alkyl) -0-C (0) - ( Ci-Cß alkyl) (Ci-Ce alkyl) -0-C (0) -, (Ci-Ce) -0-C (0) - (Ci-Ce) alkyl-0, (Ci-Ce alkyl) - OC (O) -, (Ci-Cß alkyl) -0-C (0) - (Ci-Ce alkyl) -0-C (0) -, diacylarnino (Ci-Cß), -C (0) NH- ( Ci-C-alkyl), (Ci-C-alkyl) -0-C (0) -NH- (C-C6-alkyl), -NHC (0) H and -NHC (0) - (Ci-C6-alkyl); and wherein one of the phenyl radicals of the aforementioned benzhydryl may be optionally replaced by naphthyl, thienyl, furyl or pyridyl; R 13 is hydrogen, phenyl or an alkyl (Ci-Cß); or R 3 and R 13 f together with the carbon to which they are attached, form a saturated carbocyclic ring having from 3 to 7 carbon atoms in which one of said carbon atoms which is neither the point of attachment of the spiro ring nor the one adjacent to it may be optionally replaced by oxygen, nitrogen or sulfur; RIA and RIS are each independently selected from hydrogen, hydroxyl, halo, amino, oxo (= 0), cyano, hydroxyalkyl (Ci-Cß), alkoxy (Ci-Ce) alkyl (Ci-Cß), alkylamino (Ci) -Cß), dialkylanine (Ci-Cß), alkoxy (Ci-Cß) -C (0) -OH, (Ci-C-alkyl) -OC (O) -, (Ci-C-alkyl) -0-C ( 0) - (Ci-C-alkyl), (Ci-C-alkyl) -0-C (0) -, (Ci-C-alkyl) -C (O) - (C?-C6 alkyl) -0--, ( Ci-C) alkyl) -, (Ci-Cß alkyl) -CYO) - (Ci-Ce alkyl) -, and the radicals defined in the definition of R 12; R16 is NHC (0) R18, NHCH2RI8, S02Rlβ, GR20, C02 H or one of the radicals defined in any of the definitions of R 2, Ri * and Ris; R17 is oxirnino (-NOH) or one of the radicals defined in any of the definitions of Ri2 t Ri4 and RIS; Y R e is an alkyl (Ci-Cß), hydrogen, phenyl or alkyl phenyl (Ci-Cd); G is selected from the group consisting of CH2, nitrogen, oxygen, sulfur and carbonyl; R20 is a monocyclic or bicyclic heterocycle selected from the group consisting of pyrimidinyl, benzoxazolyl, 2,3-dihydro-3-oxobenzoisosu.lfonazol-2-yl, rnorfolin-1-yl, thiomorpholin-1-yl, benzofuranyl , benzothienyl, indolyl, isoindolyl, isoquinolinyl, furyl, pyridyl, isothiazolyl, oxazolyl, triazolyl, tetrazolyl, quinolyl, thiazolyl, thienyl and the groups of formulas wherein B and D are selected from carbon, oxygen and nitrogen, and B and D at least one is other than carbon; E is carbon or nitrogen; n is an integer from 1 to 5 and any of the carbons of (CH2) n or (CH2) n +? may be optionally substituted with an alkyl (Ci-Cß) or a spi (C2-C6) alkyl and either any carbon atoms of said (CH2) n and ÍCH2) n +? cited, could be linked by a bridge through a union of one or two carbon atoms, or any pair of adjacent carbon atoms of said (CH2) n and (CH2) n +? cited can form, together with one to three carbon atoms that are not part of the ring containing the carbonyl, a fused carbocyclic ring (C3 ~ Cs); with the proviso that (a), when rn is 0, one of Rie and 1 is absent and the other is hydrogen, (b) when R3 is a group of formula VIII, Rl * and R s can not be attached to it carbon atom, (c) when Rl * and Ris are joined to the same carbon atom, then, or Rl * and R e are joined to the same carbon atom, then, ol * and RI5 are each independently selected from hydrogen, fluorine, an alkyl (Ci-Cé), a hydroxyalkyl (Ci-Cß) and an alkoxy (Ci-C) alkyl (Ci-Cß), o and RIS / together with the carbon atom to which they are attached, form a saturated carbocyclic ring (C3-C6) that forms a spiro compound with the ring containing the nitrogen to which they are attached; (d) R12 and Ri3, both can not be hydrogen; (e) when R * or Ris is attached to a carbon atom of X * of group VII or to a carbon atom of (CH2) > - of group VIII adjacent to the nitrogen atom of the ring, then Rl * or Ras, respectively, must be a substituent in which the point of attachment is a carbon atom; (f) when said compound is a group 1e formula Id or a group of formula le or le, wherein AA or AAA, respectively, is femlo optionally substituted with 1, 2 or 3 groups selected from alkyl (Ci-Cß) , fluoromethane, halo, cyano, nitro, alkoxy (Ci-Cß), tnfluororne + oxy and -S (0) v -alkyl (Ci-Ce) in which v is zero, one or two and R3 is a group of formula VII in which R3 is hydrogen and R1 is phenol, naphthyl, +? in? lo, furyl, pyridyl, thiazolyl, tetrazole, qumolyl, benzh drilo or benca lo and Ri2 is optionally substituted with alkyl (C? ~ Ce), trifluoromethyl, alkoxL (Ci-Cß), alkoxy (Ci-Cß) or halo, then at least one of Rl * and Ri5 must be different from hydrogen, alkyl (Ci-Ce), oxo, halo, -COOH, -COOalkyl (Ci-C6)) or femlo optionally substituted with alkyl (Ci-Cß), halo or t-rifluorome; and (g) ni Ri *, Ris, Rie r Ri7 can form a ring with R 3; or a pharmaceutically acceptable salt of said compound. The condensed bicyclic nucleus of the compounds of formula Ib, to which U is attached and the side chain -CH2NR2R3 may be, but is not limited to, one of the following groups: benzoxazolyl, benzothiazolyl, benzoimidazolyl, benzo soxazolyl, benzoisothiazolyl, indazolyl, ndolyl, isoquinolinyl, benzofup or, benzothienyl, oxindole, benzoxazolinomide, benzothiazolommonyl, benzoirnidazolinomide, benzoirnidazolinimin, dihydrobenzothis-S, -diox, benzotriazolyl, benzodiadiazolyl, benzoxadiazolyl and quinazolinyl. The term "halo", as used herein, includes, unless otherwise indicated, chlorine, fluorine, bromine and iodine. The term "alkyl", as used herein, includes, unless otherwise indicated, saturated monovalent hydrocarbon radicals having linear radicals, branched or cyclic or combinations thereof. The term "alkoxy", as used, includes -0-alkyl groups, wherein alkyl is defined as above. The term "one or more substituents", as used herein, includes one to the maximum possible number of substituents based on the number of available binding sites. The most specific embodiments of this invention relate to the above procedure for the treatment of cancer, wherein the NK-1 receptor antagonist is a compound as defined in any of paragraphs (1) to 2) below, or one of the pharmaceutically acceptable salts of said compound. (1) A compound of formula la or Ib in which the substituents of the positions "2" and "3" of the ring containing the nitrogen of R 3 are in a cis configuration. (When R3 is a group of formula VII or VIII, "a cis configuration", as used herein, means that the substituent which is not hydrogen of the "3" position is in cis with respect to Ri). (2) A compound of the formula wherein R3 is a? Irupo of formula III, VII or IX, R2 is hydrogen; A is phenyl or indolinyl; U is a (C 1 -C 3) alkoxy optionally substituted with from one to five fluorine atoms; and R is thiazolyl, imidazolyl, thiadiazolyl, pyrrolyl or oxazolyl, and R may be optionally substituted with one or two (C? -C3) alkyl radicals. (3) A compound of formula Ib in which R3 is a group of formula III, VII or IX; R is hydrogen; the condensed bicyclic ring system to which Ul is attached and the side chain -CH2NR2R3 / is benzoxazolyl, benzoisoxazolyl, benzothiazolyl or benzoimidazolyl; and U is an alkoxy (Ci-Cß) optionally substituted with from one to five fluorine atoms. (4) A compound as defined in paragraphs 1, 2 or 3 above in which: (a) R3 is a group of formula III and R9 is benzhydryl; (b) R3 is a group of formula VII, Ri2 is phenyl, each R3, Ri *, R5 and R1 is hydrogen, rn is zero and X * is -CH2) 3 ~; or (c) R3 is a group of formula IX, r is two and R9 is benzhydryl. (5) A compound of the formula wherein: (a) R3 is a group of formula III in which the substituents of the "2" and "3" positions of the nitrogen containing ring are in the cis, R9 configuration is benzhydryl and A is phenyl; or (b) R3 is a group of formula VII, wherein R12 and the substituent of the "3" position of the ring containing the nitrogen are in the cis configuration, A is phenol, R1 is phenyl, each of R, RI3, Rl *, Ris and R'ß is hydrogen, rn is zero, U is rnetoxyl or isopropoxyl, X * is ~ (CH2 3- and R is thiazolyl, imidazolyl, pyrrolyl, oxazolyl or thiadiazolyl. (6) A compound of formula Ib, in which R3 is a group of formula IX in which the substituents of the positions "2" and "3" of the ring containing the nitrogen are in the cis configuration, Rl * is benzhydryl, r is do and the fused bicyclic ring system to which U is attached and the side chain -CH2MR2R3, is benzoisoxazolyl or benzothiazolyl. (?) A compound of formula Ib, wherein R3 is a group of formula IX, Ris is benzhydryl, the of bicyclic fused ring to which they are attached U and the side chain -CH2NR2R3, is benzoisoxazolyl and U is rnetoxilo. (8) A compound of formula Ib, where R3 is a group of formula VII, RIA is phenyl, each "je RI3, Rl *, Ris and Rie is hydrogen, rn is zero, X * is - (CH2) 3- and the bicyclic ring system is condensed to which U is attached and the side chain -CH2HR2R3 / is benzothiazole, benzoxazolyl or benzoirnidazolyl. (9) A compound of formula la, wherein R3 is a group of formula VII, each of Ri3, Ri ", R s and Ri6 is hydrogen, m is zero, X * is - (CH2) 3 ~, A is phenyl, U is methoxy and R is selected from thiazolyl, imidazolyl, thiadiazolyl and isoxazolyl. (10) A compound of formula le, wherein R 3 is a group of formula II, III VII or IX; R2 is hydrogen; the AA ring is phenyl or indolinyl; W1 is a (C1-C3) alkoxy optionally substituted with one to three fluorine atoms; and Rl is a S (0) w-to the uilo (C1-C10) in which v is zero, one or two, S (0) «- aryl in which v is zero, one or two, -0-aryl , (Ci-Cι alkyl) -N-SO 2 - (C 1 -C 10) alkyl, wherein both or one of the alkyl radicals may be optionally substituted by one to three fluorine atoms; -Ni SO 2 -alkyl (C? -C?) 2 or (C1-C10 alkyl) -NS? 2-aryl, wherein the aforementioned aryl is phenyl or benzyl and may be optionally substituted with from one to three substituents selected independently from one another alkyl (C? -C "), a (C1-C4) alkoxy, an alkoxy (Ci-C *) and a halo. (11) A compound - as defined in paragraph 10 above, wherein R3 is a group of formula II, or is two and R * and R7 are each phenyl. (12) A compound as defined in paragraph 10 above, wherein R3 is a group of formula VII, each RI3, R: t RIS and Rie is hydrogen, R12 is phenyl, m is zero and X * is - (CH2) 3-- (13) A compound as defined in paragraph 10 above, wherein R3 is a group of formula IX, R19 is benzhydryl and r is two. (14) A compound as defined in paragraph 10 above, wherein R3 is a group of formula III, R8 is other than hydrogen and R9 is benzhydryl. (15) A compound of formula I in which the substituents of positions "2" and "3" of the ring containing the nitrogen are in the cis configuration. (16) A compound of formula le, wherein R 3 is a group of formula II wherein the substituents of positions "2" and "3" of the ring containing the nitrogen are in the cis configuration, or are two , Rβ and R7 are each phenyl and the AA ring is phenyl or indolinyl. (17) A compound of formula le, wherein R 3 is a group of formula III, in which the substituents of positions "2" and "3" of the ring containing the nitrogen are in the cis configuration, R 8 it is other than hydrogen, R9 is benzhydryl and the AA ring is phenyl. (18) A compound of formula le wherein R3 is a group of formula VII in which Ri and the substituent of the "3" position of the ring containing the nitrogen are in the cis configuration, the AA ring is phenyl, Ri2 is phenyl, each of R2, I3, Rl *, Ris and Ie s hydrogen, rn is zero, X * is -ÍCH2) 2 ~ or -ÍCH2) 3- and R1 is selected from a -S (o) v - (C 1 -C 10) alkyl and that v is zero, one or more, and one (Ci-Cι alkyl) -N-S 2 - (C 1 -C 10 alkyl) and dialkilanino (Ci-C 6). (19) A compound as defined in paragraph 18 above, in which X * is ~ (CH2) 2 ~ and w * is an alkoxy (Ci-Cß) optionally substituted with one to three fluorine atoms. (20) A compound as defined in paragraph 18 above, wherein X * is -CH2 3 ~ and UH is an alkoxy (Ci-Cß) optionally substituted with one to three fluorine atoms. (21) A compound of formula le, wherein R3 is a group of formula IX, in which the substituents of positions "2" and "3" of the ring containing the nitrogen are in the cis configuration, r is two and Rl9 is benzhydryl. (22) A compound as defined in paragraph 21 above in which the AA ring is phenyl, UJi is an alkoxy (Ci-Cß) optionally substituted with one to three fluorine atoms and R is selected from an -S ( 0) v -alkyl (C1-C10) where v is zero, one or two, an alkyarin (Ci-Cß), dialkylamino (Ci-Cß) and a (C 1 -C 10 alkyl) -N-SO 2 - (Ci-cyl aqluyl) - (23) A compound as defined in paragraph 15 above, wherein the AA ring is phenyl, UJi is an alkoxy (Ci-Cß) optionally substituted with one to three fluorine atoms and Ri is selected from an -S (0) v - (C1-C10) alkyl in which v is zero, one or two, and a (C 1 -C 10 alkyl) -N-SO 2 - (Ci-Cι alkyl) - (24) A compound as defined in paragraph 15 above, wherein the AA ring is phenyl, UJi is an alkoxy (C? Cé) optionally substituted with one to three fluorine atoms and R 1 is selected from arnino, an alkylamino (Ci-Cß) or a dialkylamino (Ci-Cß). (25) A compound as defined in paragraph 12 above, wherein the AA ring is phenyl and R1 is selected from -S (0) v- (C1-C10) alkyl wherein v is zero, one or two and one ^^ I (C1-C10 alkyl) -N-SO2 - (Ci-Cio alkyl) - (26) A compound of formula I, wherein R3 is a group of formula III, ring AA is phenyl, UJi is an alkoxy (Ci-Cß) optionally substituted with one to three fluorine atoms and Ri is selected from amino, an alkylamino (Ci-Cß) or a dialkylamino (Ci-Cß). (27) A compound as defined in paragraph 24 above, in which Ul is attached to the "2" position of the AA ring and Rl is attached to the "5" position of the AA ring, with respect to the binding point of the side chain that contains the NR2 R3. (28) A compound as defined in paragraph 25 above, in which Wi is attached to the "2" position of the AA ring and Rl is attached to the "5" position of the AA ring, with respect to the binding point of the side chain that contains the. NR2R3. (29) A compound as defined in paragraph 25 above, in which UJi is attached to the "2" position of the AA ring and Rl is attached to the "5" position of the AA ring, with respect to the point of attachment of the side chain that contains the NR2R3. (30) A compound as defined in paragraph 23 above, in which UH is attached to the "2" position of the AA ring and Rl is attached to the "5" position of the AA ring, with respect to the binding point of the lateral one that contains the NR2 R3. (31) A compound as defined in paragraph 13 above, in which the AA ring is phenyl, C is selected from isopropoxyl, OCF3, OCH3, OCHF2 and OCH2CF3, and R1 is selected from an -S (0) w - (C1-C10) alkyl wherein v is zero, one or two and one (C1-C10 alkyl) -N-SO2- (C? -C? alkyl) - (32) A compound of formula le, wherein R3 is a group of formula VII, rn is zero, each of R3, Ris, Rie and R1 s is hydrogen, R1 is phenyl, R1 * is -Cio) -OH, ring AA is phenyl, U1 is a (C 1 -C 3) alkoxy and R 1 is selected from a (C 1 -C 5) alkyl, -SCH 3, SO 2 CH 3, a alkylamino (Ci-Cβ) and a dialkylamino (Ci-Cß). (33) A compound of formula le, which has the formula (34) A compound of formula Id, wherein R6, R7, R o, Rll and R13 are phenyl, R8 is hydrogen, R9 is a phenyl optionally substituted with chloro, fluoro, an alkyl (Ci-Cs) optionally substituted with one to three fluorine atom or an alkoxy (Ci-Cß) optionally substituted with one to three fluorine atoms, is O and K is 3 or 4. (35) A compound of formula Id, wherein R3 is a group of formula II, wherein o is two or three and R * and R ? are each phenyl or a substituted phenyl. (36) A compound of formula Id, wherein R3 is a group of formula III, R8 is hydrogen and R9 is phenyl or a substituted phenyl. (37) A compound of formula Id, wherein R3 is a group of formula IV, wherein I is one or two and Rio and RH are each phenyl or substituted phenyl. (38) A compound of formula Id, wherein R3 is a group of formula V, wherein k is zero or one and Rio and RH are each phenyl or substituted phenyl. (39) A compound of formula Id, wherein R3 is a group of formula VI, wherein p is one and Rio and Rll are each phenyl or substituted phenyl. (40) A compound of formula Id, wherein R3 is a group of formula VII, wherein q is two, three or four, rn is zero and Ri2 is phenyl or substituted phenyl. (41) A compound of formula Id, wherein R3 is a group of formula VIII, wherein y is zero, x ee zero or one, z is three or four, m is zero and Ri2 is phenyl or substituted phenyl. (42) A compound of formula Id, wherein R 3 is a group of formula VII, R 1 *, R 3, R 1 and R s are hydrogen, Ri 2 is phenyl, is 2-methoxy, X 2 and β 3 are independently selected from hydrogen, chlorine, fluorine, methyl, an alkoxy, iCi-Cß) and trifluoromethyl, rn is 0 and q is 3 or 4. This invention also relates to a process for treating cancer in a mammal, including a human, which comprises administering to said mammal a therapeutically effective amount of an NK-1 receptor antagonist of a compound having the formula wherein U is Y or X (CH2) n; Y is an optionally substituted (Ci-Cß) alkyl, optionally substituted (C 2 -C 2) alkenyl or optionally substituted C 3 -C 8 -alkyl; X is an alkoxy (Ci-Cβ) optionally substituted hydroxyl, CONR R2, C02R1, CHR10R2, CHR1NR2R3, C0R1, CONRl 0R2 or an optionally substituted aryl, wherein said aryl is selected from phenyl, naphthyl, pyridyl, quinine! i.lo, thienyl, furyl, phenoxyphenyl, oxazolyl, tetrazolyl, thiazolyl, imidazolyl and pyrazolyl; and n is an integer from zero to six; Ari, Ar and Ar3 are each, independently, an optionally substituted aryl, wherein said aryl is selected from phenyl, naphthyl, pyridyl, quinolyl, thienyl, furyl, phenoxyphenyl, oxazolyl, tetrazolyl, thiazolyl, .imidazolyl and pyrazolyl.; and R1, R3, R3 are independently selected from hydrogen, an optionally substituted Ci-C2 alkyl), an optionally substituted (Ci-Cβ) alkoxy, optionally substituted C3-Ce (C3-cycloalkyl), an optionally substituted aryl, wherein said aryl is selected from phenyl, naphthyl, pyridyl, quinolyl, thienyl, furyl, phenoxyphenyl, oxazolyl, tetrazolyl, thiazolyl, imidazolyl and pyrazolyl; and optionally substituted heterocyclic (C3-C5) groups, wherein said heterocyclic groups are selected from pyrrolidino, piperidino, morpholino, piperazinyl and thi morphino; and wherein the substituents of the preceding alkyl, alkenyl, cycloalkyl and alkoxy groups are independently selected from halo, nitro, amino, alkyls (C? ~ C, <), (C1-C4) alkoxyls, trifluoromethyl and trifluorornetoxy.lo; and wherein the substituents of the preceding heterocyclic (Cß-Cs) groups are attached to the sulfur or nitrogen atom of the ring and are independently selected from oxygen, dioxygen and alkyls (C? -C ") when attached to the sulfur atom of the ring, and are independently selected from oxygen, and alkyls (C1-C4) when a ring nitrogen atom is attached; and wherein the substituents of the aforementioned substituted Ari groups are independently selected from alkyls (Ci-Cs) optionally substituted with one to three halo groups, alkoxyls (Ci-Cß) optionally substituted with one to three halo groups, alkylsulfinyls ( Ci-Cß), alkenyls (Ci-Cß), thioalkyls (Ci-Cß), alkylsulfonyl (Ci-Cß), alkylsulfonylaminos (Ci-Cß) and dialkylaminos (Ci-Cß) in which one or both alkyl groups can be optionally substituted with an alkylsulfonyl group (Ci-Cß) or an alkylsulfinyl (Ci-Cß); and wherein the substituents of said substituted Ar2 and Ar3 groups are independently selected from (C1-C4) alkyls, (C1-C4) alkoxyls, (C1-C4) thioalkyls, (C1-C4) alkylsulfinyls, dialkylaminos (Ci -Cu), trifluoromethyl and trifluoromethoxy; with the proviso that when Y is unsubstituted or substituted by an alkyl (C? -C "), it is attached to position 4 or 6 of the quinuclidine ring; Other more specific embodiments of this invention relate to a method of treating cancer described above, wherein the NK-1 receptor antagonist is a compound as defined in any of paragraphs (43) to (48) below. , or one of the pharmaceutically acceptable salts of said compound. (43) A compound of formula X in which Ul is X (CH2) n - (44) A compound of formula X in which Ul is Y. (45) A compound of formula X in which Ari is a substituted aryl and W is Y. (46) A compound of formula X in which Ari is a mono-, di- or trisubstituted phenyl and U is Y. (47) A compound of formula X in which Ar 1 is a disubstituted phenyl in the positions 2 and 5 and W is Y. (48) A compound of formula X in which Ari is paranetoxyphenyl, Ar2 and Ar3 are each phenyl and ee Y. This invention also relates to a method for treating cancer in a mammal , including a human, which comprises administering to said mammal a therapeutically effective amount of an NK-1 receptor antagonist which is a compound of formula wherein? i is a (C1-C5) alkoxy or a halo (C1-C5) alkoxy; X is hydrogen, a halogen, a (C1-C5) alkyl, a (C2-C5) alkenyl, a (C2-C5) alkynyl, an alkoxy (Ci-Cs), a thioalkyl (C1-C5), an alkylsulfinyl (C1) -C5), a (C1-C5) alkylsulfonyl, a halo-substituted (C1-C5) alkyl, a halo-substituted (C1-C5) alkoxy, a (C1-C5) alkylamino, a dialkylamino having from one to five carbon atoms in each alkyl radical, an alkylsulfonylamino (Ci-Cs) (which may be substituted by a halogen), (Ci-Cs alkyl) -N- (C1-C5 alkylsulfonyl) (which may be substituted by a halogen in the radical, alkylsulfonyl), or a (C1-C5) alkanoylamino (which may be substituted by a halogen) or (C 1 -C 5 alkyl) T-N- (C 1 -C 5 alkanoyl) (which may be substituted by a halogen in the alkanoyl radical); Ari and Ar2 are each, independently; thienyl, phenyl, fluorophenyl, chlorophenyl or bromophenyl; U3 is - (CH2) m -CH (R2) - (CH2) n ~ NR1-; R1 is hydrogen, a (C1-C5) alkyl, benzyl or - (CH2) P-Y; R2 is hydrogen, a (C1-C5) alkyl (which may be substituted by a substituent selected from the group consisting of hydroxyl, amino, thiomethyl and mercapto), benzyl, 4-hydroxybenzyl, 3-indolyl-phenyl or - (CH2) p-Y; And it is -CN, -CH2Z or -COZ; Z is hydroxyl, amino, a (C 1 -C 5) alkoxy, a (C 1 -C 5) alkylamino or a dialkylamino group having from one to five carbon atoms in each alkyl radical; m, n and p are each, independently, 0, 1, 2 or 3; and R1 and R2 can be connected to form a ring; or a pharmaceutically acceptable salt of said compound. The terms "halogen" or "halo" are used above in formula XV to refer to fluorine, chlorine, bromine or iodine. The term "alkyl" is used above in formula XV to refer to straight or branched chain hydrocarbon radicals including, but not limited to, methyl, s-butyl, t-butyl, and the like. The term "alkenyl" is used above in formula XV to refer to straight chain or branched hydrocarbon radicals having a double bond including, but not limited to, ethenyl, 1- and 2 -propene, 2- I give you 1.-1 ™ propenyl, 1- and 2-butenyl and the like. The term "alkynyl" is used above in formula XV to refer to straight chain or branched hydrocarbon radicals having a triple bond including, but not limited to, ethynyl, propynyl, butynyl, and the like. The term "alkoxy", is used above in formula XV to refer to -OR3 (R3 is alkyl), including, but not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, t- butoxyl and the like. The term "thioalkyl", is used above in formula XV to refer to -SR * (R * is alkyl), including, but not limited to, thiomethyl, thiotelo, thio-n-propyl. thioisopropyl, thio-n-butyl, thioisobutyl, thio-s-butyl, thio-t-butyl and the like. The term "alkylenylfinyl" is used above in formula XV to refer to -SOR5 (R5 is alkyl including, but not limited to, methylsulfinyl, ethylsulfinyl, propylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, strybutylinyl, t-butylsulfinyl and the like The term "alkylsulfonyl" is used above in formula XV to refer to -SO2R6 (R6 is alkyl) including, but not limited to, rnethyl sulfonyl, ethyl sulphonyl, propyl sulfonyl, n-butyl sulphonyl, isobutyl sulphonyl, s-butyisul fonyl, t-butylsul fonyl and the like The term "alkylsulfonylamino (which may be substituted by a halogen)" is used above in formula XV to refer to -NHSO2R7 (R7 is alkyl which may be substituted by a halogen) , including, but not limited to, methyldulfonylamino, ethylsulfonylamino, trifluoromethylsulfilamino and the like The term "N-alkyl-N-alkylsulfonylamino (which may be substituted by a halogen in the alkylsufonyl radical)" is previously used in formula XV to refer to -N (R8) S02R9 (R8 is alkyl and R9 is alkyl which may be substituted by a halogen), including but not limited to N-rnethylsulphonylamino, N-ethyl-N-methylsuifonylamino, Nn-propyl-N-rnetylsulfonylamino, N-isopropyl-N-rnetylsulfonylamino, N-ethyl- N-tri fluoromethylsulfonyl. -propyl-N-tri fluoromethyl sulphonic acid, N-isopropyl-N-trifluoromethylsulphonilane and the like. The terms "alkylamino" and "dialkylamino" are previously used in formula XV to refer to -N (R10) RII (RIO is hydrogen or alkyl and RH is alkyl) including, but not limited to, meti. lamino, ethylamino, n-propylamino, isopropylarnino, n-butylannino, t-butylamino, dirnet i lamino, diethylamino, ethylamino and the like. The term "alkanoylamino" (which may be substituted by a halogen) is used previously in the formula XV to refer to -NHC0R12 (Ri2 is alkyl which may be substituted by a halogen) including, but not limited to, form i. lamino, acetylamino, propionylamino, butir.ilarni.no, isobutyrylamino, trifluoroacetylamino and the like. The term "N-alkyl-N-alkanoylamino" (which may be substituted by a halogen in the alkanoyl radical) "is used above in formula XV to refer to -N (R 3) CORi * (R 3 is alkyl and R * is alkyl which may be substituted by a halogen) including, but not limited to, N-acetyl-N-ritylamino, N-acetyl-N-ethylarylene, N-acetyl-N-propylamino, N-acetyl-N -ethylamino, N-acetyl-Nn-propylamino, N-acetyl-N-isopropylamino, N-trifluoroacetyl-N-methylamino, Nt-ri 1 -acetoacet-1-N-etiyl, N- t-ri-1-uoroacet i 1-N-propylamino, Nt i fluoroacet i 1-N-isopropyl.arni.no and the like The term "alkyl substituted with halo" is used above in formula XV to refer to an alkyl radical as described above substituted with one or more halogens including, but not limited to, chlorohexyl, trifluoromethyl, 2,2,2-trichloroethyl and the like The term "halo substituted alkoxy" is used above in formula XV to refer to n radical alkoxy as described above substituted with one or more halogens including, but not limited to, chloronetoxyl, trifluoromethoxy, 2,2,2-trichloroethoxy and the like. This invention also relates to a method of treating cancer in a mammal, including a human, which comprises administering to said mammal a therapeutically effective amount of a receptor antagonist NK-1 which is a compound of formula wherein R is a phenyl optionally substituted with one or more substituents, preferably with one to three solvents, independently selected from hydrogen, a halo, nitro, an alkyl (Ci-Cio) optionally substituted with one to three fluorine atoms , an (Ci-C ?o) alkoxy optionally substituted with one to three fluorine, hydroxyl, phenyl, cyano, amino atoms, an alkylamino (Ci-Cß), a dialkylol (Ci-Cß). -C (0) -NH- (Ci-C-alky), (Ci-C-alkyl) -C (0) -NH- (Ci-C-alkyl), an alkoxy (Ci-C ") -alkyl (C? -C «).

-S (0) w -phenyl in which v is zero, one or two, -S (0) v -benzyl, -E¡? 2NR * R5 in which each of R * and R5 is, independently , an alkyl (Ci-Cs), or R * and Rs, together with the nitrogen to which they are attached, form a saturated ring containing a nitrogen and from three to six carbons, (Ci-Cι alkyl) -N-SO 2 - (C 1 -C 10 alkyl) in which one or both alkyl radicals may be optionally substituted with one to three fluorine atoms, -N (S 0 2 - C 1 -C 0 alkyl) 2, (C1-C10 alkyl) -N-S02-phenyl and (C? -C? alkyl) -N-S02-benzyl; and wherein any of the phenyl radicals of the above Rl groups may be optionally substituted with one to three substitutes independently selected from (C1-C4) alkyl, (C1-C4) alkoxy and halo; or Ri is phenyl substituted with a group having the formula wherein a is 0.1 or 2 and the asterisk represents a meta position with respect to the point of attachment of R1 to structure XVI; R2 is selected from an alkyl (Ci-Cß) line! or branched, a (C3-C7) cycloalkyl in which one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; an aryl selected from biphenyl, phenyl, indanyl and naphthyl; a heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxaszolyl, isoxazolyl triazolyl, tetrazolyl and quinolino; alkyl (C2-Ce) phenyl, benzhydryl and benzyl, wherein each of the aryl and heteroaryl groups mentioned and the phenyl radicals of said benzyl, (C2-C) alkyl phenyl and benzhydryl can be optionally substituted with one or more substituents, preferably with one to three substituents, independently selected from halo, nitro, a (C 1 -C 10) alkyl optionally substituted with one to three fluorine atoms, a (C 1 -C 10) alkoxy optionally substituted with one to three fluorine atoms, amino, a hydroxy (C 1 -C 6) alkyl, an alkoxy (Ci -Ce) alkylene (Ci-Cß), an aikil ino Cß), (Ci-Ce alkyl) -0-C- (0) -, (Ci-C-alkyl) -0-C (0) - (Ci-Cß alkyl), (Ci-C-alkyl), (Ci-alkyl) -Ce) -C (O) -O-, (Ci-C-alkyl) -C (0) - (Ci-C-alkyl) -C (O) -, (Ci-C-alkyl) -C (0) - ( Ci-C alkyl) - (Ci-C6 alkyl) -C (0) -NH- (alkyl Ci -6), -NHC (0) H and -NHC (O) - (Ci-C alkyl); and wherein one of the phenyl radicals of the aforementioned benzhydryl may be optionally replaced by naphthyl, thienyl, furyl or pyridyl; m is an integer from 0 to 8, and any of the simple carbon-carbon bonds of (CH2), in which both carbon atoms are bonded together and to another carbon atom in the chain (Cl-m, may be optionally replaced by a carbon-carbon double bond or a carbon-carbon triple bond and any of the carbon atoms of said (CH2) m may be optionally substituted with R *; R3 e selects from NHC (0) R8, NHCH2 R8, SO2R8, AR9, CO2H and the radicals that define the definitions of R2, R6 and R7; A is CH2, nitrogen, oxygen, sulfur or ca rbon.ilo, - R * is selected from oxirnino (~ N0H) and the defined radicals in the definitions of R2, RS and R7 • Rβ is an alkyl (Ci-Ce), hydrogen, phenyl or an alkyl (Ci-C) enyl; R9 is a monocyclic or bicyclic spherical hetero selected from the group consisting of pyrimidinyl, benzoxazolyl, 2,3-yl-3-oxo-benzoisosulfonazolo-2-yl, rnorfolin-1-yl, thiomorpholin-1-yl, benzofuranyl, ben nzothienyl, indolyl, isoindolyl, isoquinoliniio, furyl, pyridyl, isothiazolyl, oxazolyl, triazalyl, tetrazolyl, quinolyl, thiazolyl, thienyl and the groups of formulas ) n +? wherein B and D are selected from carbon, oxygen and nitrogen, and B and D at least one is other than carbon; E is carbon or nitrogen; n is an integer from 1 to 5, any of the carbons of (CH2) n or (CH2) n +? it may be optionally substituted with an alkyl (Ci-Cß) or a spiroalkyl (C2-C6), and either any pair of carbon atoms of said (Cl-fein and (CH2) n + [beta]] may be attached through a bridge by a union of one or two carbon atoms, which are not members of the ring containing the carbonyl, a condensed carbocyclic ring (C3 -C5); X is (CH2) q, where q is two or three, and that one of the simple carbon-carbon bonds of said (CH2) q may optionally be replaced by a carbon-carbon double bond, and wherein any of the carbon atoms of said (CH2) q may be optionally substituted with R6 , and wherein any of the carbon atoms of said (CH2) may be optionally substituted with R7; Rβ and R7 are independently selected from hydrogen, hydroxyl, a halo, amino, oxo (= 0), cyano, a hydroxyalkyl (Ci-Cß), an alkoxy (Ci-Ce alkyl) (Ci-Ce), an alkylamino (Ci-Cß), dialkylamino (Ci-Cß), alkoxy (Ci-Cß), -C (0) -0H, (Ci-C-alkyl) -OC- (O) -, (Ci-C-alkyl) -0-C- (0) - (Ci-Ce alkyl) , (C 1 -C 6 alkyl) -C- (0) -, (C 1 -Ce alkyl) -C (O) - (C 1 -C 6 alkyl) -0-, C 1 -C e alkyl) -C (0) - , (C 1 -C 7) alkyl (0) - (C 1 -Ce alkyl), and the radicals defined in the definition. R2; and Y is (CH2) ?, where z is zero to one; with the proviso that: (a) when A is - (CH 2) - or carbonyl, R 9 can not be furyl, pyridyl, isothizole, oxazolyl, triazolyl, tetrazolyl, quinolyl, thiazolyl or thienyl; (b) when m is zero, of R3_ and R * one is absent and the other is hydrogen; (c) when RS or R7 are attached to a carbon atom of X that is adjacent to the ring nitrogen, then R6 or R7, respectively, must be a substituent in which the point of attachment is a carbon atom; and (d) when A is N, O or S, R9 is not mor-folin-1-yl or thiornorpholin-1-yl; or a pharmaceutically acceptable salt of said compound. This invention also relates to a method of treating cancer in a mammal, including a human, which comprises administering to said mammal a therapeutically effective amount of an NK-.l receptor antagonist which is a compound of formula X V I I wherein ri and Ar2 are each independently an aryl or a substituted aryl; Ri is an alkyl having 1 to 6 carbon atoms; R2 is hydrogen or an alkyl having 1 to 6 carbon atoms; and either X and Y are separately and are each, independently, hydrogen, a dialkylphosphoryl having from 2 to 12 carbon atoms, an alkenyl having from 1 to 6 carbon atoms or an alkenyl having from 2 to 6 carbon atoms; or an alkynyl having from 2 to 6 carbon atoms; or X and Y are taken together and represent a hydrocarbon chain having 3, 4 or 5 carbon atoms, optionally containing up to two double bonds and having optionally 1 or 2 substituents selected from oxo, hydroxyl and a alkyl having from 1 to 6 carbon atoms; with the proviso that when X and Y are taken together they are attached to adjacent carbon atoms; and with the proviso that if X or Y is hydrogen, then the other must be an alkenyl or an alkynyl; or a pharmaceutically acceptable salt of said compound. The term "alkyl" is used above in formula XVIII to refer to straight or branched chain hydrocarbon radicals including, but not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl and similar. The term "alkenyl" is used above in formula XVII to refer to straight or branched chain hydrocarbon radicals having a linkage including, but not limited to, ethenyl, 1- and 2-pro-enyl, 2-rneti.l-.l-propenyl, 1- and 2-butenyl and the like. The term "alkynyl" is used above in formula XVII to refer to straight chain or branched hydrocarbon radicals having a triple bond including, but not limited to, ethynyl, propynyl, butynyl, and the like. The term "aryl", formerly used in formulas XVII to refer to aromatic radicals, include "or, but not limited to, phenyl, naphthyl, pyridyl, quinolino, thienyl, furyl, oxazolyl, tetrazolyl, thiazolyl, pyrazolyl, and the like. alkyl, alkoxy, thioalkyl, halogen, cyano, nitro, phenoxy. , mono- or dialkylamino and the like as substituents on the aryl. The term "alkoxy", is used above in formula XVII to refer to -OR3 (R3 is alkyl), including, but not limited to, rnetoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, t-butoxy and the like. The term "halogen" is used above in formula XVII to refer to radicals derived from the elements fluorine, chlorine, bromine and iodine. The term "thioalkyl" is used in formula XVII to refer to an -SR * (R * is an alkyl) including, but not limited to, thiomethyl, thioethyl, thio-n-propyl, thioisopropyl, thio-n-butyl, thioisobutyl, thio-t-butyl and the like. The term "dialkylphosphoryl" is used in formula XVII to refer to a -PIO) (ORS) (OR-) (RS and R6 are an alkyl) including, but not limited to, diethylphosphoryl, ethylrnenylphosphoryl, and the like. other more specific embodiments of this invention relate to a method for treating cancer, described above, wherein the NK-1 receptor antagonist that is administered is a compound as defined in any one of paragraphs (49) to (51) below, or one of the pharmaceutically acceptable salts of said compound. (49) Compounds of formula XVII in which Ari and Ar2 are each phenyl, R1 is methyl, R2 is hydrogen, X is an alkenyl or an alkynyl and Y is hydrogen. (50) Compounds of formula XVII wherein Ari and Ar2 are each phenyl, R1 is methyl, R2 is hydrogen and X and Y are each an alkyl. (51) Compounds <Formula XVII in which Ari and Ar 2 are each phenyl, R 1 is methyl, R 2 is hydrogen and X and Y represent CH 2 CH 2 CH 2 or CH 2 CH 2 CH 2 CH 2. This invention also relates also to a method of treating cancer in a mammal, including a human, which comprises "administering to said mammal a therapeutically effective amount of an NK-1 receptor antagonist which is a compound of formula XVIII wherein Ari and Ar2 are each independently, thienyl, phenyl, fluorophenyl, chlorophenyl or bromophenyl, -X is -C0NR3R *, -C02 R3, -CH20R3, ~ CH2NR3R * or -C0NR30R *; R1, R3 and R * are each, independently, hydrogen or an alkyl having 1 to 4 carbon atoms; R2 is an alkyl having 1 to 4 carbon atoms; Y is an alkylsulfonyl having from 1 to 4 carbon atoms, an N-alkyl-N-alkanoylamino (which may be substituted with a halogen in the alkanoyl radical) having from 1 to 4 carbon atoms in the alkyl and alkanoyl radicals , an N-alkyl-N-alkylsulfonylamino (which may be substituted with a halogen in the alkylsufonyl radical) having from 1 to 4 carbon atoms in the alkyl and alkylsulfonyl radicals, an alkenyl having from 2 to 4 carbon atoms, an alkynyl having from 2 to 4 carbon atoms, an alkyl substituted with halo having from 4 carbon atoms, an alkylamino having from 1 to 4 carbon atoms, an alkanoylamino (which may be substituted with a halogen) has 1 to 4 atoms < carbon or an alkylsulfonylamino (which may be substituted with a halogen) having .1. to 4 carbon atoms; or a pharmaceutically acceptable salt of said compound. The term "alkyl" is used above in formula XVIII to refer to straight or branched chain hydrocarbon radicals including, but not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl and sirnilaree; The term "alkenyl" is used above in formula XVIII to refer to straight or branched chain hydrocarbon radicals having a double bond including, but not limited to, ethenyl, 1- and 2-propenyl, 2-methyl- 1 -propenyl, 1- and 2-butenyl and the like. The term "alkynyl" is used above in formula XVIII to refer to straight chain or branched hydrocarbon radicals having a triple bond including, but not limited to, ethynyl, propynyl, butyne and the like. The term "alkylenyl fonyl" is used above in formula XVIII to refer to -SO2RS (RS is alkyl) including, but not limited to, methylsul fonyl, ethylsul fonyl, n-propylsulphony, isopropylsul fonyl, n-butylsulfonyl, isobutylsulfonyl, t-butylsulfonyl and the like. The term "alkylamino" is used above in formula XVIII to refer to -NHR- (Rβ is alkyl) including, but not limited to, ritylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, t-butylamino and the like. The term "alkanola ino" is used above in formula XVIII to refer to -NHCOR7 (R7 is alkyl or alkyl substituted by a halogen) including, but not limited to, forrnilarnino, acetylamino, propylamino, butyrylamino, isobutyrylamino, trifluoroacetylamino and the like. The term "alkylsufonylamino" is used above in formula XVIII to refer to -NHSO2R8 (R8 is alkyl or alkyl substituted by a halogen), including, but not limited to, methylsulphonylamino, ethylsulfonylamino, tri fluoromethylsulphonylamino, and the like. The term "N-alkyl-N-alkylsulinylamino" is previously used in the formula XVIII to refer to -N (R9) S0-2Rio (R9 is alkyl and R or is alkyl or substituted alkyl < Jo by a halogen), including, but not limited to, N-rnethyl-N-rnethyl sulphonylamino, N-ethyl-N-methylsulphonylamino, N-phenyl-N-methylsulphonylamino, N-isopropyl-N-methylsulphonylamino, N-rnethyl - N- 1 ri f 1 uo romet i 1 - sul f oni lami no, N-et i 1 -N- 1 ri f luo ronet i 1 -sulfonilarnino, Nn? Rop.il-N-trifluoromethylsulfonilarnino and Ni sop rop i 1-N-1-fluoromorph.1-sulphonylamino The term "N-alkyl-N-alkanoylamino" is used above in formula XVIII to refer to -N (RH) C0Ri2 (Rii is alkyl and Rl2 is alkyl or alkyl substituted by a halogen) including, but not limited to, N-acetyl-N-rnetilarnihno, N-acetyl-N-ethylamino, N-acetyl-Nn-propylamino, N- acetyl-N-isopropylarnino, N-tri-fluoroacetyl-N-ethylarnino, N-trifluoroacetyl-Nn-propylarnino and N-tri-fluoroacetyl-N-isopropylamino. Other more specific embodiments of this invention relate to the method for treating cancer, described above, wherein the NK-1 receptor antagonist that is administered is a compound as defined in the paragraphs (52) to (57) below, or one of the pharmaceutically acceptable salts of said compound. (52) A compound of formula XVIII in which Ari and Ar2 are ca-one phenyl. (53) A compound as described in paragraph (52) wherein R 2 is methyl and R 1 is hydrogen. (54) A compound as described in paragraph C53) wherein X is in the 3-position of the quinuclidine ring and X is carboxyl or aminocarbonyl. (55) A compound as described in paragraph (54) wherein Y is said alkenyl. (56) A compound as described in paragraph (55) wherein Y is isopropenyl. (57) A compound as described in paragraph (56) wherein Y is methylsul fonyl, N-acetyl-N-methylamino or N- and i1-N-methylsiloxane. This invention also relates to a method of treating cancer in a mammal, including a human, which comprises administering to said mammal a therapeutically effective amount of an NK-1 receptor antagonist which is a compound of formula MX wherein R is an alkyl (Ci-Ce); X is an alkyl (Ci-Ce) having one or more substituents through a heteroatom; Ari and Ar2 are each, independently, an aryl optionally substituted by an alkyl (Ci-Cß), an alkoxy (Ci-Ce), a thioalkyl (Ci-Ce), a halogen, cyano, nitro, phenoxy, a monoalkylamino (Ci-Cß), a dialkylamino (Ci-Cß), a substituted (Ci-Cβ) halo or a halo (C? -Cß) halosubstituted; Y is hydrogen, an alkyl (Ci-Ce), an alkenyl (C2-Ce), a cycloalkyl (C3-C8), a Z- (CH2) p-, or a U- (CH2) «- CHR2- (CH2 ) n -NRiCO- in which Y is in the 4-, 5- or 6-position of the quinuclidine ring; Ri is hydrogen, an alkyl (Ci-Cß), benzyl or a (CH 2) r-UJ; R2 is hydrogen or an alkyl (Ci-Ce) which may be substituted by a hydroxyl, amino, thiomethyl, mercapto, benzyl, 4-hydroxybenzyl, 3-indolylmethyl or a - (CH2) r ~ UJ; Z is an alkoxy (Ci-Cß), -C0NR * R5, -CO2R *, -CHR * 0RS, -CHR * N5R6R, -COR *, -C0NR * 0RS or an optionally substituted aryl; each Ul is independently cyano, hydroxymethyl, a (C2-C6) alkoxymethyl, arninonetyl, a rnonoalkyl (Ci-ds) arninornetyl, a dialkyl (Ci-Ce) aminomethyl, carboxyl, carbamoyl or an alkoxycarbonyl (Ci-Cß); R *, RS and RS are independently hydrogen, an alkyl (Ci-Cß), an alkoxy (Ci-Cß), a cycloalkyl (C3-C8) or a heterocyclic or optionally substituted aryl group; p is 0 to 6; and m, n and r are each, independently, from 0 to 3; or a pharmaceutically acceptable salt of said compound.

Other, more specific embodiments of this invention relate to the method for treating cancer, described above or in which the NK-1 receptor antagonist which is added is a compound as defined in the paragraphs. (58) to (60) below, or one of the acceptable pharmaceutically acceptable salts of said compound. (58) A compound of formula XIX in which X is an alkyl (Ci-Cß) having one or two substituents selected from h-hydroxyl, a halogen, an alko lo (Ci-Cß), an alkanoyl (C2-C6) ), an alkanoyloxane (C2-C6), a thioalkyl (Ci-Cß), a rnonoalkaline (C? ~ Ce), a dialkylamino (Ci-Cß), a mo, cyano and acid. (59) A compound of formula XIX as described in paragraph (58) in which R is methyl and the group OR is in the 2-position; A1-1 and Ar2 are each femlo, rnonoclorofemlo or rnonofluorofena it; Y is hydrogen or Z- (CH2) p-, wherein Z is an alkoxy (Ci-Cß), -C0NR * RS, -CO2R *, -CHR * 0R5, -CHR * NR5R6, COR * or -C0NR * 0R5; and Y is in position 5- or fa ~. (60) A compound such as is described in paragraph (59), wherein X is an altjuyl (Ci-Ce) having one or two + »-u u u u u u u u seleccionados seleccionados seleccionados entre Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci. and a thioalkyl (Ci-Cß); Ari and Ar2 are each phenyl; and Y is hydrogen or carboxyl. This invention also relates to a method of treating cancer in a mammal, including a human, which comprises administering to said mammal a therapeutically effective amount of an MK-1 receptor antagonist which is a compound of formula XX wherein X and Y are each hydrogen, a halo, a (C1-C6) alkyl, a halo-substituted (Ci-Cβ) alkyl, an alkoxy (C? ~ Ce), a thioalkyl (Ci-Cß), an alkylsulfonyl (Ci-Ce), a fonquile alquisul (Ci-Ce), or a trialkysilyl (Ci-Cß); ARi and Ar-2 are each an aryl optionally substituted by a halo; A is -CO- or ~ (CH2) -; Z-A- is in position 5 or 6 «Jel ring of qninucidin; Z is hydroxyl, an alkoxy (Ci-Ce), NRiR2 or UJi - (CH2) m- CHR * - (CH2) n -NR3 wherein R1 and R2, when taken separately, are each hydrogen or an alkyl (Ci-Cß); R1 and R2, when taken together with the nitrogen atom to which they are attached, represent piperidino, pyrrolid, morpholino, iornorfolino or piperazino; R 3 is hydrogen, an alkyl (Ci-Cé), benzyl or - (CH 2) r-UI 2; R * is hydrogen or an alkyl (Ci-Cß) which may be substituted by hydroxyl, arnino, thiomethyl, mercapto, benzyl, 4-hydroxybenzyl, 3-indolimethyl or - (CH-2) g -U > 3; R3 and R *, when taken together, represent CH2 O CH2 CH2; Uii, W and U3 are each, independently, cyano, hydroxymethyl, a (C1-C6) alkoxymethyl, arninornetyl, methyl (Ci-ekylamino), methyl (dialkylamino CiC &), carboxyl, carbamoyloalkyl Ci-Ce ), or carbarnoyl (dialkyl Ci-C), carba oyl or carboniKalcoxyl Ci -C & ); and m, n, r and s are each 0.1.2 or 3; or a pharmaceutically acceptable salt of said compound. As used in formula XX, the term "thioalkyl" refers to an -S-alkyl, including but not limited to thiomethyl, thioethyl, and the like. As it is used in formula XX, the term "alkylsulfinyl" refers to an -SO-as-alkyl, including but not limited to methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, and the like. As used in formula XX, the term "alkylsulfonyl" refers to an -SO 2 -alkyl, including but not limited to methylsul fonyl, ethylsulfonyl, isopropylsulfonyl, and the like. As used in formula XX, the term "aryl" refers to aromatic radicals, including but not limited to phenyl, naphthyl, pyridyl, quinolino, thienyl, furyl, oxazolyl, tetrazolyl, thiazolyl, imidazolyl, pyrazolyl, and the like. These aryl groups can be substituted with an alkyl (Ci-Cß), an alkoxy (Ci-Cß), a thioalkyl (Ci-Cß), halogen, cyano, nitro, phenoxy, ono- or dialkylamino (Ci-Cß) and Similar. This invention also relates to a method for treating cancer in a mammal, including a human, which comprises administering to said mammal a therapeutically effective amount of a Nk-1 receptor antagonist which is a compound of formula XXI wherein Y is an alkylene (C2-C4); Z is a valence bond or an alkylene (Ci-Cß); R 1 is phenyl, biphenyl, indanyl, naphthyl, thienyl, furyl, pyridyl, thiazolyl, isothiazolium, oxazolyl, isoxazolyl, tetrazolyl, quinolyl, an alkyl (Ci-Cß) phenyl or benzhydryl, wherein each of the ring-shaped radicals can optionally being substituted by one or more substituents independently selected from a halogen, an alkyl (Ci-Ce), a substituted alkyl (Ci-Ce), an alkoxy (Ci-Cß) and a haloxy (Ci-Cß) halosubstituted; R2 is hydrogen or an alkyl (Ci-Cß); R3 is hydrogen, hydroxyl, cyano, amino or carboxyl, with the proviso that when Z is a valence bond, R3 must be hydrogen; R * represents a group of formula (XXII) (XXIII) XXII xx i p in which Xa; X2 and 33 are each halo, hydrogen, nitro, an alkyl (Ci-Ce), a halo-substituted (Ci-Ce) alkyl, an alkoxy (Ci-Ce), a halo-substituted alkoxy (Ci-Ce), hydroxyl, amino, a thioalkyl (Ci-Cß), an alkylsulfinyl (Ci-Ce) or a fonical alquisul (Ci-Cß); 0a and O2 are each H2, oxygen or sulfur; A is a valence, methylene, oxygen, sulfur or NH bond; RS and R6 are each hydrogen or an alkyl (Ci-Cé); R7 is hydrogen, a halogen, an alkyl (Ci-Cß), a (Ci-Cß) -galosubstituted alkyl or an alkoxy (Ci-Ce); or a pharmaceutically acceptable salt of said compound. The term "halo", as used above in formula XXI, includes fluorine, chlorine, bromine and iodine. The term "alkyl", as used above in formula XXI, includes saturated monovalent hydrocarbon radicals having straight, branched or cyclic radicals or combinations thereof. The term "alkenino", as used above in formula XXI, refers to straight or branched chain hydrocarbon radicals having a double bond including, but not limited to, ethenyl, 1- and 2-pro-enyl , 2-methyl-1-propenyl, 1- and 2-butenyl. The term "alkoxy", as used above in formula XXI refers to ~ 0-alkyl, in the. which alkyl is defined as above, and includes, but is not limited to, rnetoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutyl, and t-butyloxy. The term "thioalkyl", as used above in formula XXI, refers to -S-alkyl, wherein alkyl is defined as above, and includes, but is not limited to, thiomethyl, thioethyl, thio-n-propyl, thioisopropyl, thio-n-butyl, thioisobutyl and thio-t-utilo. The term "cycloalkyl", as used above in formula XXI, unless otherwise indicated, refers to cyclic hydrocarbon radicals including, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "one or more substituents", as used above in formula XXI, includes one to the maximum possible number of substituents based on the number of available binding sites. The compounds of formulas I, X, XV, XVI, XVII, XVIII, XIX, XX and XXI contain asismetric centers and therefore exist in different enantiomeric forms. The above definitions of these compounds include all optical isomers and all stereoisomers of such compounds and mixtures thereof. One or more specific embodiments of this invention relate to any of the above methods for treating cancer, wherein the NK-1 receptor antagonist that is administered is selected from the group consisting of: (2S, 3S) -3 - (5-tert-butyl-2-methoxybenzyl) amino-2- (3-tri fluoromethoxy phenyl) pi? Eridin; (2S, 3S) -3- (2-i.S or p r or p or x i -5-t-fluoromethoxybenzyl) arnino-2-phenylpiperidine; (2S, 3S) -3- (2-Ethoxy-5-trifluoromethoxybenzyl) amino-2-phenylpiperidine; (2S, 3S) -3- (2-rnetox i-5- 1 ri f 1 or rornetox ibenci 1) arni no-2-phenylpiperidi a; (2S,: 3S) -3 ~ (5-tert-butyl-2-t ri fl uo rornetox ibenci 1) ami no-2-phenyl pi pe ri. di na; 2- (di-phenylmethyl) -N- (2-methoxy-5-tri-f-chloro-ethoxy phenyl) rr-ethyl-1-azabicyclo-C2.2.2Hoct.an-3-yna.na; (2S, 3S) -3-C5-chloro-2- (2, 2, 2-trifluoroethoxy i) encyl] - my non-2-pheni 1 p i. pe ri d na; (2S, 3S) -3- (5-tert-butyl-2-t ri f 1 or rornetox i benz 1) a i no-2-f eni 1 pi pe ri di na; (2S, 3S) -3- (2-isopropoxy-5-tri f 1 or rornetox i benc i 1) arni non-2-phenyl 1 pi pe ri. di na; (2S, 3S) -3- (2-di f 1 uo r-ometox i -5-1 lr f 1 uo rometox i benc i 1) ami or 2- phenyl pipe ridine; (2S, 3S) -2-phenyl-3 ~ [: 2- (2,2,2-trifluoroethyoxybenzyl)] - arninopiperidine; (2S, 3S) -2- phenyl -3- (2-trifluoro-ethoxy-encyl) -a i -pep i d i na; cis -3- (2-chlorobenzylamino) -2- phenyl piperidine, • cis -3- (2-tri-fluoromethylbenzylamino) -2-f e n i 1 p i pe r i d i na; cis-3- (2-methoxybenzyl) .no) -2- (2- fluorofen.il) -pipe ridine; cis-3- (2-methoxybenzyl mino) -2- (2-chlorophenyl) -p i pe ridine; C-3 ~ (2-methoxy, benzyllamino) -2- (methylphenyl) -piperidine; cie-3- (2-methoxy-benzylamine) -2- (3-rnetoxy phenyl) -pi and ridine, - cis-3- (2-methoxybenzylani.no) - 2 - (3-f luoro phenyl.) -piperidine; cis- 3 - (2-ethoxy i en i lami) -2- (3-chlorophenyl) -piperidine; cis -3- (2-methoxybenzylamino) -2- (3-methyl pheni.1) -piperidine, cis-3- (2-r-methoxybenzyl-cinnamino) -2- (-fluorophenyl) -piperidine; cis-3- (2-rnetox ibenci lamino) -2- (3-thienyl) piperidine; cis -3- (2-methoxybenzylamino) -2-phenylazacycloheptane; 3- (2-rnetox.ibencilarnino) -4-me-il-2-phenylpiperidine; 3- (2-r-methoxy-benzylamino) -5-methyl-2-phenylpiperidine; (2S, 3S) -l- (5-ca rboetox i pent-1-i 1) -3- (2-methoxy-benzyl-amino) -2-phenylpiperidine; (2S, 3S) -l- (6-hydroxyl? Xl-1) -3- (2-methoxybenzyllamino) -2- phenylpiperiine, - (2S, 3S) -l- (4-hydroxy-4-phenylbutyl) 1-yl) -3- (2-methoxybenzylamino) -2-phenylpiperidine; (2S, 3S) -l- (4-oxo-4 ~ phenylbut-1-yl) ~ 3- (2-methoxybenzyl arnide) -2-phenyl 1 pi pe ri di na; (2S, 3S) -l- (5,6-dihydroxyhex-l-yl) -3- (2-methoxybenzyl-ami no) -2-phenyl-1-piperidine; cis -3- (5-fluoro-2-methoxybenzylamino) -2-phenyl-piperidine; (2S, 3S) -l-C4- (4-fluorophenyl) -4-oxobut-1-yl] -3- (2-methoxy-benzyl) -2-f in. i.1 pi per i di na; (2S, 3S) -l- [2- (4-fluorophenyl) -4-hydroxybutyl-1-yl] -3- (2-methoxy-lamino) -2-phenypiperidine; ci s - 3 - (2-methoxy i-5-rnet i 1 benci larni no) - -f enil pipe ridi a; (2S, 3S) -1- (4 ~ benzamodobut-l-yl) -3- (2-rnetox.ibenzyl-arni no) -2-pheny1 pi peri-di; cis -3- (2-nitroxybenzylamino) -2-phenypiperi a; (2S, 3S) -3- (2-methoxybenzylamino) -l- (5 ~ N-rnet.ii ~ carboxamidopentyl-l) -2-phenylpipermine; (2S, 3S) -1- (4-cyanobutyl-1-yl) -3- (2-methoxy-benzylane not) • 2-phenylpiperidine; (2S 3S) -l-C4- (2-naphthamido) b? T-l-yl] -3- (2-rnetoxybenzyl-arnino) -2-phenylp? Eri.Dina; (2S, 3S) - .1. - (5-benzarni dopent-i-i 1 -) 3 - (2-nitroxybenzyl) -1-a ino) -2-phenylpiyridin; (2S, 3S) -2- (5 -ami nopent-1-i 1) -3- (2-methoxy-benzylane, no) • 2- phenyl-piperazine; (2S, 3S) -3- (5-Chloro-2-methoxybenzylamino) -2-phenyl-1-pyridione; (2S, 3e) -3- (2,5-dimethoxybenzylamino) -2-f in i 1 p i pe ri di na; ci s- 3 - (3, 5-di f 1 uoro-2-methoxy benzyllarni) -2-piperidine; cis- 3- (4, 5-di-fluoro-2-rnetox-ibenci-lamino) -2-fe or 1-pi pe ridine,-cis-3- (2,5-dimethoxybenzylamino) -1-C4- (4 - fluorofeni 1) 4 -oxobut • - 1 - i.1] - 2 - f eni 1 pipe ri di na; cis -3- (5-chloro-2-r-methoxybenzylamino) -1- (5, 6-di hi d rox i hex-1-i 1) -2-pheny1 pi pe ri. di na; cis -3- (5,6-dihydroxyhex-1-yl) -3- (2, 5-dimethoxy and benzyl non-2-phenyl) piperidine; cis-2-phenyl-3- [2-pro? -2-yloxy) benzylamino] -piperidine; cis -3- (2,5-dimethoxybenzyl) amino-2 - (3-nithexyphenyl) -piperidine; cis -3- (5-chloro-2-methoxybenzyl) amino-2 -3-rnetoxyphenyl) piperidine; cis -3- (5-chloro-2-methoxybenzyl) amino-2 - (3-chlorophenyl) piperidine; 3 - (2rnetox i benci lami no) 2, 4 - di feni 1 pi pe ri. di na; c.i.s-3- (2-methoxybenzylamino) -2- phenyiiropyrrolidine; (2S, 3S) ~ 3 ~ (5-et i.1- -methoxedin I) arnino ~ 2 ~ phenyl 1 pipe ridine; (2S, 3S) ~ 3- (5-n-butyl.l -2-methoxy-benzyl) amino-2-phenyl-1-piperidine; (2S, 3S) - 3 - (2-methoxy-5-n-p ropi benz.1) am i no - 2-pheny1-p i pe r i di na; (2S, S) -3- (5-isopro-yl-2-methoxybenzyl) amino-2-phenylpiperidine; (2S, 3S) ~ 3- (5-s-butyl-2-rnetox ibenci 1) my non-2- eni 1 pi pe ri di. na (2S, 3S) -3- (5-t-Butyl-2-methoxybenzyl) arnino-2-phenylpiperidine; (2S, 3S) -3- (2-rnetox i-5-phenyl-1-benzyl) -non-2-phenylpiperidine; [4-rnetoxy-3 - ((2S, 3S) -2-phenylpiperi din -3-i-laminomethyl) phenyl-2-methyl-4-dimethylthiazole-5-sulfonic acid; N- (4,5-dirnetyl-thiazol-2-yl) -N-C4-methoxy-3- ((2S, 3S) -2-phenyl-iperidin-3-yl-amino-methyl) -phenyl -methane-sulphonic acid; . { 5-C (4,5 ~ dimethylthiazol-2-yl) ritylamino] -2-rnetoxybenzyl} - ((2S, 3S) -2-phenylpiperidin-3-yl) amine; . { 5- (4,5-dimethylthiazol-2-ylamino) -2-methoxybenzyl} ~ ((2S, 3S) -2-phenyl? Iperidin-3-yl) arnin; methyl- [3- ((2S, 3S) -2-phenylpiperidin-3-ylaminomethyl) -1- (4-trifluoronetoxy phenyl) -amide of 4,5-dimethylthiazole-2-phonic acid; R4-isopropoxy-3- ((2S, 3S) -2- phenylpiperi din-3-ylamininornethyl) phenyl] -netyl amide of 2,4-dimethylthiazole-5-sulfonic acid; C4-isopropoxy-3- ((2S, 3S) -2-phenylpiperi din-3-ylamininornethyl) phenyl] isopropylamide of the hyyl-2, 4-dimethylthiazole-5-syphonic acid; 2,4-Dimethylthiazole-5-sulphonic acid C4-rnetoxy-3- ((2S, 3S) -2-phenylpiperidin-3-ylaminornetyl) phenyl3-isopro-ylamide; 6. 1 [4-rneto i -3 ~ ((2S, 3S) -2- phenyl? I? Eridin-3-yl inomethylDisobutylarnide of 2,4-dirnethylthiazole-5-sulphonic acid; C4-ieopro? Oxy-3- ((2S , 3S) -2-phenyl-iperidin-α-aminomethyl) phenyl 3 -sumicyl 2-, 4-dirnethylthiazole-5-sulphonic acid (2S, 3?) ~ N- (5-i sop ropi 1 - 2 - methox i. feni.1) rnet i 1 - 2 -diphenylmethyl-l-azabicycloC2 .23octan-3 -amine; (2S, 35) -N- (5 -te rc- buti 1 - 2-methoxy and feni 1) methyl-2-diphenylmethyl-1-azabicycloC2.2.23octan-3 -amine; (2S, 3S) -N- (a-meth i 1 -2-methoxy-1-phenyl) rnet and 1-2-diphenylmethyl-1- azabicyclo [2.2.2 octan ~ 3 ~ arnin; (2S, 3S) -N- (5-ethyl-2-methoxy-phenyl) methyl-2-di-phenyl-1-azabicycloC2.2.2] octane-3 ~ arnine; (2S, 3S) -N- (5 ~ i-sopropyl-2-rnetoxy phenyl) methyl-2-d., phenyl-1-azabi-C, 2.2.23-octane-3-amine; , 3S) -N- (5-sec-butyl-2-rnetoxyphenyl) rnet.il-2-diphenyl-ethyl-l-azabicycloC2.2.23octan-3 -amine; (2S, 3S) -N- (5- n- propi 1 - 2-methox. L feni 1) rnet i 1 - 2 -d.ifeni.lrne til-l-azabicycloC2.2.23octan -3-arnine; (2S, 3S) -2-di-phenyl-1-methyl-3- (5-t-trc-buty: l-2-methoxy-benzyl) -amino-yl-azabicycloC2.2.23 octane; (2S, 3S) -N-C5- (l-cyano-l-methylethyl) -2-methoxybenzyl-2-f eni 1 pi pe ri di n-3-amine; (2S, 3S) -3 ~ (6 ~ rnet? Xi-l-methyl-2-oxo-l, 2, 3, 4-tet rahydroquinol, in-7-yl) met i 1-2-phenylpiperi di-3 -amine; (2S, 3S) -2-phenyl-N-C5-r2.2.2-trifluoro-l- (t ri f 1 uorornet i 1) et i 1-2-methoxy benzyl pi pi id n- 3 -arni na; (2S, 3S) -2- i enylmet.il -N-C2-rnetoxy-5- (methylsulfonyl) -benz 13-1 -azabi cyclo C2.2.23 octan-3-amine; (2S, 3S) -2-diphenylmethyl-N- (5-isopropenyl-2-rnetoxybenzyl) -l-azabicycloC2, .2.23octan-3-arnin; (2S, 3e) -2-diphenylmethyl-N- [5- (l-hydroxy-l-methylethyl) 2-2-methoxybenzyl] -l-azabicycloC2.2.23octan-3-amine; (3R, 4S, 5S, 6S) -N, N-diethyl-5- (5-isopropyl-2-rnetoxy-benzylamino) -6- di-pheni. Irnetyl-l-azabicycloC 2.2.23 octan-3-c rboxamide; (3R, 4S, 5S, 6S) -N, N-diethyl-5- (2,5-dirnetoxybenzylamine) -6-di phenylmethyl-1-azab.icicl.oC2.2.23octan-3-carboxamide; (3R, 4S, 5S, 6S) -5- (5-iso? ropil-2-methoxy-benzyl-amino) -6-diphenylmethyl-1-azabicycloC2.2.2 octan-3-cat-oxo-1-yl; (3R, 4S, 5S, 6S) -5- (2-methoxy-2'-netthiobenzyl-a-ino) -6-diphenylmethyl-1-azabicycloC2.2.23octane-3-catboxylic acid; (3R, 4S, 5S, 6S) -5- (2,5-dimethoxy-benzylamino) -6-diphenylmethyl-1-azabicyclo [2.2.2 octane-3-carboxylic acid; (3R, 4S, 5S, 6S) -5- (2-rnetoxy-5-methylbenzylamino) -6-di-phenyl-1-methyl-azabi-C-2,2.23-octane-3-caboxylic acid; (3R, S, 5S, 6S) -5- (5-ethyl-2-methoxybenzylamino) -6- d.phenylmethyl-1-azabicycloC2.2.23octan-3-catboxylic acid; (3R, 4S, 5S, 6S) -5- (2-methoxy-5-n-pro? ilbenzylamino) -6-diphenylmethyl-1-azabicycloC2.2.23 octane-3-catboxylic acid; (3R, S, 5S, 6S) -5- (5-sec-bUtil-i. rnetoxiber? cilarn.ino) -6-diphenyl-phenyl-l-azabicycloC2.2.2 octan-3-catbox.il acid. ico; (3R, 4S, 5S, 6S) -5- (5-N-rnethyl-methanesulphonarinyl) 2-methoxybenzylamino) -6-diphenylmethyl-1-azabi [2.2.23 octanecaboxylic acid; (3R, 4S, 5S, 6S) -5- (2-methoxy-5-methylsulfinylbenzylamino) -6-di-phenylmethyl-1-azabicyclo [2.2.23 octane-3-carboxylic acid; (3R, 4S, 5S, 6S) -5 ~ (2-methoxy-5-tri-fluoromethoxy-benzylamino) -6-di-phenylmethyl-1-azabi-cyclo-C2.2.23-octane-3-caboxylic acid; 'Jo (3R, 4S, 5S, 6S) -5- (2-methoxy-5 rpet i.1 sul f oni 1 benci lami no) - 6- dif eni 1 rnet i 1 - 1 -azabic.iclo [2.2 .23 octane-3-catboxylic; Acid (3 R, 4 S, 5?, 6 S) -5 - (5-di-nit-i-lami-2-nitro-i-benz-1-one) -6- di-phenyl-meth i. I-l-azabicycloC2.2"23octan-3-catboxili.co; (3R, 4S, 5S, 6S) -5 ~ (5-isopropyl-2-methoxybenzylamine) -6-di-phenyl-phenyl-1-azab.icicl.oC2.2.23-octane-3-catboxylic acid; (3R, S, 5S, 6S) -5- (2-Methoxy-5-methylthiobenzylamine) -6-diphenylmethyl-1-azabicycloC2.2.23 octane-2 cat oxy. lico (3R, 4S, 5S, 6S) -5- (2,5-dimethoxybenzylamino) -6-diphenylmethyl-1-azabicyclo 2.2.23 octane-3-carboxylic acid; (3R, 4S, 5S, 6S) -5- (2-methoxy-5-rnethylbenzylamine) 6-di phenylmethyl-1-azabicycloC2.2.23 octane-2-catboxyl acid; (3R, 4S, 5S, 6S) - 5 - (5-ethyl-2-r-methoxybenzylamino) -6-diphenylmethyl-1-azabicycloC2.2.23 octane-3-catboxylic acid; Acid (3 R, 4 S, 5 S, 6S) - 5 - (2-methoxy-5-n- p ropi.1 benz.1-arnin) -6-d-phenylphenyl-l-azabicycloC2.2.23octan -2-cat oxil.ico; (3R, 4S, 5S, 6S) -5- (d-sec-butyl-2-methoxybenzyl-1-amino) -6-diphenylmethyl-l-azabicyclo 2.2H 23 octan-2-cat box, acidic (3R, S, 5S, 6S) -5- (5-N-rnetylmet nosul foni lami or -2-rnetoxibencilarnino) -6-difenilrneti.ll ~ azabicicloC2.2.23octan-2-catboxíico; (3R, 4S, 5S, 6S) ~ 5- (2-rnetox-5-methyl-sulphon-1-benzylamino) -6-diphenylmethyl-1-azabicyclo 2.2.23 octane-2-catboxylic acid; (3R, 4S, 5S, 6S) -5- (2-rnetoxy-5-trifluorornetox-benzylamino) -6-diphenylmethyl-1-azabicycloC2.2.23octan-2-c-carboxylic acid; (3R, 4S, 5S, 6S) -5- (2-methoxy-5-metisul fonylbenzyl-amino) -6-di-phenyl-1-methyl-1-azabi-cylo C 2.2. 3 octane-2-carboxylic; and (3R, 4S, 5S, 6S) -5- (5-dimethylamino-2-r-methoxy-benzyl-ami) -6-di-phenyl-phenyl-yl- acid. I-azabicycloC 2.2.23 octan-2-carboxylic; and the pharmaceutically acceptable salts of the above compounds.

DETAILED DESCRIPTION OF THE INVENTION The compounds of the formulas la, Ib, le, Id, le, X, XV, XVI, XVII, XVIII, XIX, XX and XXI can be prepared as described below. Unless indicated otherwise, in the following "scripture, the structural formulas la, Ib, le, Id, le, X, XV, XVI, XVII, XVIII, XIX, XX and XXI and groups II, III, IV, V, VI, VII, VII, IX, XXII and XXIII are as defined above. The compounds of formula la and Ib can be prepared as described in U.S. Patent Application 968,653, which was filed on December 10, 1992. This application is incorporated herein by reference in its entirety. Compounds of formula le can be prepared as described in patent application US 932.392, which was filed on 19 August 1992 and Patent Application PCT / US 93/09407, which designates the United United and presented at the United States Ticket Office on October 7, 1993 and published as UO 94/13663 on June 23, 1994. These applications are hereby incorporated by reference in their entirety. Compounds of formula Id can be prepared as described in PCT Patent Application PCT / US 92/03571, which designates the United States and was filed with the United States Bureau of Entries on May 5, 1993 and which was published as UO 93/00331 on January 7, 1993. This application is incorporated herein as an antecedent in its entirety. The compounds of formula I can be prepared as described in U.S. Patent Application 123,306, which was filed on September 17, 1993 and PCT Patent Application PCT / IB 94/00221, which designates the United and presented at the International Office on July 18, .1994. This application is incorporated herein as a background in its entirety. When R3 is a group of formula II, the starting materials of formula NH2R3 which are used in the preparation of compounds of the formulas la, Ib, le, Id and le can be prepared as described in the Patent of the United States Units 5,162,339, which was granted on November 11, 1992. This patent is incorporated herein by reference in its entirety. When R3 is a group of formula III, the starting materials of formula NH2R3 which are used in the preparation of the compounds of formulas la, Ib, le, Id and le can be prepared as described in the PCT Patent Application. PCT / US 91/02853, which designates the United States and was filed with the United States Ticket Office on April 25, 1991 and published as UO 91/18899 on December 12, 1991. This application is incorporates the present as a whole antecedent.

When R3 is a group of formula IV, V or VI, the starting materials of formula NI-I2 R3 which are used in the preparation of compounds of the formulas la, Ib, le, Id and le can be prepared as described in PCT Patent Application PCT / US 91/03369, which designates the United States and was filed with the United States Ticket Office on May 14, 1991 and published as UO 92/01688 on June 6. February 1992. This application is incorporated herein by reference in its entirety. When R3 is a group of formula VII, the starting materials of formula NH2R3 which are used in the preparation of the compounds of formulas la, Ib, le, Id and le can be prepared as described in the Patent of the United States of America. US 5,232,929, which was granted on August 3, 1993, Patent Application of the United States 800,667, filed 27 November 1991 Patent Application PCT / US 91/02451, which designates the United United submitted to the Office of the United States Entries on April 12, 1991 and published as UO 91/18878 on December 12, 1991 and PCT Patent Application PCT / US 92/00065, which designates the United States, was filed with the United States Bureau of Commerce on January 14, 1992 and published as WO 92/17449 on October 15, 1992. These applications are hereby incorporated by reference in their entirety. When R3 is a group of formula VIII, the starting materials of formula NH2R3 which are used in the preparation of the compounds of the formulas la, Ib, le, Td and le can be prepared as described in the PCT Patent Application PCT / US 91/05776, which designates the United States and was filed with the United States Bureau of Entries on August 20, 1991 and published as UO 92/06079 on April 16, 1992; U.S. Patent 800,667, filed November 27, 1991 and PCT Patent Application PCT / US 92/00065, which "sent to the United States, was filed with the United States Ticket Office on January 14. of 1992 and which was published as UJO 92/17449 on October 15, 1992. These applications are incorporated herein by reference in their entirety. When R3 is a group of formula XI, the starting materials of formula NH2R3 which are used in the preparation of the compounds of formulas la, Ib, le, Id and le can be prepared as described in the patent application of United States Serial No. 719,884, filed June 21, 1991 and PCT Patent Application PCT / US 92/04697, which designates the United States and which was filed with the United States Bureau of Entries on June 11, 1992 and that was published as UO 93/00330 on January 7, 1993. These requests are incorporated into the foregoing as an antecedent in its entirety. The compounds of formula X can be prepared as described in PCT Patent Application PCT / US 92/04002, which designates the United States, was filed with the United States Ticket Office on March 19, 1992 and which was published as UO 92/15585 on September 17, 1992. This application is incorporated herein as an antecedent in its entirety. The compounds of formula XV can be prepared by being described in PCT Patent Application PCT / US 92/04002, which designates the United States, was filed on March 1, 1992 and was published as WO 92/20676 on October 26. November <; je 1992. This application is incorporated herein as an antecedent in its entirety. Compounds of formula XVI can be prepared as described in U.S. Patent Application 026,382, filed April 7, 1993, and PCT Patent Application PCT / US 93/11793, which designates the United States. and that it was filed with the United States Ticket Office on December 10, 1993 and published as UlO 94/20500 on June 15, 1994. These applications are hereby incorporated by reference in their entirety. The compounds of formula XVII can be prepared as described in PCT Patent Application PCT / US 93/09169, which designates the United States and which was filed with the United States Bureau of Entries on September 30, 1993 and it was published as UO 94/10170 on 11 < the rnayo of 1994. This application is hereby incorporated in its entirety in its entirety. The compounds of formula XVIII can be prepared as described in PCT Patent Application PCT / US 93/09168, which designates the United States and which was filed with the United States Bureau of Entries on September 30, 1993. and it was published as UO 94/08997 on April 28, 1994. This request is incorporated herein and in its entirety in its entirety. The compounds of formula XIX can be prepared as described in PCT Patent Application PCT / 3P 94/00781, which designates the United States and which was filed with the Japan Ticket Office on May 13, 1994. This application is incorporated herein as a whole in its entirety. Compounds of formula XX can be prepared as described in PCT Patent Application PCT / JP 94/01092, which designates the United States and which was filed with the Japan Ticket Office on July 5, 1994. This application is hereby incorporated as an antecedent in its entirety. The compounds of formula XXI can be prepared as described in the Application PCT PCT / JP 94/01514, which designates the United States and which was filed with the Japan Ticket Office on September 13, 1994. This application is incorporated herein as an antecedent in its entirety. The therapeutic agents of a basic nature are capable of forming a wide variety of different salts such as various organic and inorganic acids. Examples of acids which form pharmaceutically acceptable salts suitable for use in this invention are those which form non-toxic acid addition salts, ie, salts containing pharmacologically acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate salts , bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, fluconate, saccharate, benzoate, methanesulfonate, ethanesulphonate, benzeneulphonate, p-toluenesulfonate and parnoate. , 1'-methylene-bis ~ (2-hydroxy-3-naphthoate) 3,. Although such salts must be pharmaceutically acceptable for administration to animals, in practice it is often desirable to initially isolate a therapeutic agent from the reaction mixture as a pharmaceutically unacceptable salt and then simply convert the latter back into the free base and subsequently convert the above free base in a pharmaceutically acceptable acid addition salt. The acid addition salts of the base therapeutic agents of this invention are readily prepared by treating the base compound with a substantially equivalent amount of the chosen mineral or organic acid in an aqueous solvent medium or in a suitable organic solvent, such as methanol or ethanol. After careful evaporation of the solvent, the desired solid salt is easily obtained. Those therapeutic agents of this invention which also have an acidic nature are capable of forming salts with various pharmacologically acceptable cations. The chemical bases that are used with reagents to prepare * the pharmaceutically acceptable base salts of the therapeutic agents are those that form salts <Non-toxic base with the agents - acidic therapies. Such non-toxic base salts include those derived from pharmacologically acceptable cations such as sodium, potassium, calcium and magnesium, etc. These salts can be easily prepared by treating the corresponding acidic compounds with an aqueous solution containing the desired pharmacologically acceptable cations and then evaporating the resulting solution to dryness, preferably under reduced pressure. Alternatively, they can also be prepared by mixing together lower alkane solutions of the acidic compounds and the desired alkali metal or alkoxy, and then evaporating the resulting solution to dryness in the same manner as before. In any case, stequiornene amounts of the reactants are preferably employed in order to ensure the completion of the reaction and the maximum efficiencies of the desired final product. The following references refer, < collective form, to derivatives of quinuclidine, pipepdine, ethylendia ina, pyrrolidine and azanorbornane and to related compounds that exhibit activity as substance P receptor antagonists, and can therefore be employed in the methods of this invention, and to processes for preparing the same: U.S. Patent 5,162,339, which was granted on November 11, 1992; U.S. Patent 5,232,929, which was granted on August 3, 1993; International Patent Application WO 92/20676, published on November 26, 1992; U.S. Patent Application UO 93/00331, published January 7, 1993; International Patent Application WO 92/21677, published December 10, 1992; International Patent Application WO 93/00330, published January 7, 1993; International Patent Application UO 93/06099, published on April 1, 1993, International Patent Application UO 93/10073, published May 27, 1993; International Patent Application 1 UO 92/06079, published on April 16, 1992; International Patent Application WO 92/12151, published July 32, 1992; the Inter-national Patent Application W 92/15585, published on September 17, 1992; International Patent Application WO 93/10073, published May 27, 1993; International Patent Application WO 93/19064, published September 30, 1993; International Patent Application WO 94/08997, published on April 28, 1994; International Patent Application WO 94/04496, published March 3, 1994; International Patent Application UO 94/13663, published on June 23, 1994; International Patent Application WO 94/20500, published September 15, 1994; International Patent Application PCT / IB94 / 00221, which designates the United States and was filed on July 18, 1994; International Patent Application PCT / JP94 / 00781, which designates the United States and the. May 13, 1994; International Patent Application PCT / JP94 / 01092, which designates the United States and was filed on July 5, 1994; and International Patent Application PCT / JP94 / 01514, which designates the United States and was filed on September 13, 1994. All previous applications of the International Patent designate the United States. The above patents and patent applications are incorporated as the present reference in its entirety. The specific NK-1 receptor antagonists presented in the Summary of the Invention can be prepared by methods described in the published patents and patent applications cited above, as well as in the scientific literature. Other NK-1 receptor antagonists that can be employed in the methods of this invention are those compounds and pharmaceutically acceptable salts described in the following references: European Patent Application EP 499,313, published on August 19, 1992; European Patent Application EP 520,555, published on December 30, 1992; European Patent Application EP 522,808, published on January 13, 1993; European Patent Application EP 528,495,? Ublica < ja on February 24, 1993; PCT Patent Application UO 93/14084, published July 22, 1993, PCT Application No. UO 93/01169, published January 21, 1993, -Request "PCT Patent WO 93/01165, published on 21 January 1993, PCT Patent Application WO 93/01169, published January 21, 1993, PCT Patent Application WO 92/20661, published November 26, 1992, European Patent Application EP 517,589, published December 12 of 1992, European Patent Application EP 428., 434, published on May 22, 199.1, European Patent Application EP 360,390, published on March 28, 1990, PCT Patent Application WO 95/19344, published on 20 July 1995, PCT Patent Application WO 95/23810, published September 8, 1995, PCT Patent Application WO 95/20575, published August 3, 1995 and PCT Patent Application WO 95/28418, published on October 26, 1995. In general, in carrying out the methods of this invention, the NK-1 receptor antagonist it will be administered to a human or adult in an amount ranging from about 0.07 to about 21 g per kg of body weight, of the patient being treated per day, in single or divided doses, preferably from about 0.36 to about 4.3 mg / kg. However, depending on the type of patient being treated and their individual response to said medication, variations may occur, as well as depending on the type of pharmaceutical formulation chosen and the period of time and interval at which said medication is carried out. administration. In some cases dosage levels below the lower limit of the above-mentioned range may be more than adequately, while in other cases even higher doses may be employed without causing any untoward side effects, provided that such larger doses are first divided into several doses. lower doses for administration throughout the day. The NK-1 receptor antagonists and their pharmaceutically acceptable salts that are employed in the methods of this invention are hereinafter referred to as the "therapeutic agents". The therapeutic agents can be administered either orally or paranterally. The therapeutic agents can be administered alone or in combination with pharmaceutically acceptable carriers or diluents by any of the routes indicated previously, and such administration can be carried out in single or multiple doses. More specifically, the novel therapeutic agents of the present invention can be administered in a wide variety of different dosage forms, ie, they can be combined as several pharmaceutically acceptable inert carriers in the form of tablets, capsules, tablets, lozenges that can be sucking, hard candies, suppositories, aqueous suspensions, injectable solutions, elixirs, syrups and the like. Such carriers include solid diluents or fillers, sterile aqueous media and various non-toxic organic solvents, etc. In addition, the oral pharmaceutical compositions can be duly curable and / or flavored. In general, the therapeutic compounds of this invention are present in such dosage forms at concentration levels ranging from about 5.0% to about 70% by weight. For oral administration, tablets containing various excipients such as nicrocrystalline cellulose, sodium citrate, calcium carbonate, dicalcium phosphate and glycine can be used together with various disintegrants such as starch (and preferably corn, potato or tapioca starch), alginic acid and certain silicates complexes, together with granulation binders such as polyvinylpyrrolidone, sucrose, gelatin and gum arabic. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for the preparation of tablets. Solid compositions of a similar type may also be employed as loading of gelatin capsules; In this regard, preferred materials also include lactose or milk sugar, as well as high molecular weight polyethylene glycols. When aqueous suspensions and / or elixirs are desired for oral administration, the active ingredient may be combined with various sweetening or flavoring agents, coloring substances or dyes and, if desired, also emulsifying agents and / or suspension, together with diluents. such as water, ethanol, propylene glycol, glycerin and various similar combinations thereof. For parantheral administration, solutions of a therapeutic agent may be used in sesame or peanut oil, or in aqueous propylene glycol. The aqueous solutions can be suitably buffered if necessary and first make the isotonic liquid diluent. These aqueous solutions are suitable with intravenous injection dies. Oily solutions are suitable for intraarticular, intramuscular and subcutaneous injection purposes. The preparation of all these solutions under sterile conditions is easily achieved by conventional pharmaceutical techniques well known to those skilled in the art. The activity of certain therapeutic agents as substance P receptor antagonists can be determined by their ability to inhibit the binding of substance P to receptor sites in bovine caudal tissue, using radioactive ligands to make tachykinin receptors visible by of autoradiography. The antagonizing activity of substance P of the compounds described herein can be evaluated using the standard assay procedure described by M. A. Caecieri et al., As described in the Journal of Biological Chemistry, Vol. 258, p. 5158 (1983). This method essentially involves determining the concentration of the individual compound required to reduce to 50% the quantity of ligands of substance P radio arcades, at their receptor sites in the said bovine tissues isolated, thus obtaining the characteristic CIso values of each compound tested. . In this procedure, bovine caudal tissue is dried from a freezer at -70 ° C and is homogenized in 50 volumes (w / v) of a Tris hydrochloride buffer (ie, trimetamine which is 2-amino-2-hydroxymethyl-1). , 3-propanediol) 50 rnl * 1, cooled on ice to a pH of 7.7. The homogenate is centrifuged at 30,000 x G for a period of 20 minutes. The sediment is resuspended in 50 volumes of Tris buffer, it is re-furnace and it is recentrifuged at 30,000 x G for another period of twenty minutes. The sediment is then resuspended in 40 volumes of ice-cold Tris 50 mu t-buffer (pH 7.7) containing 2 mM calcium chloride, 2 mM magnesium chloride, 4 μg / ml bacitracin, 4 μg / ml leupeptin, 2 μg. of quirnostatin and 200 μg / ml of bovine serum albumin. With this step, the tissue preparation is finished. The radioligand binding procedure is then carried out in the following manner, namely, initiating the reaction by means of adding 100 μl of the test compound to a concentration of 1 μM, followed by the addition of 100 μl of radioactive ligand to a final concentration of 0.5 mM and then finally by the addition of 800 μl of the tissue preparation produced as described above. The final volume is thus 1.0 ml and the reaction mixture is then stirred in a whirlpool and incubated at room temperature (about 20 ° C) for a period of 20 minutes. The tubes are then filtered using a cell harvester and the glass fiber filters (Uhatrnan GF / B) are washed four times with Tris 50 rnM temp (pH 7.7), the filters having previously been pre-baked for a period of two hours. before the filtration procedure. The radioactivity was then determined in a .Beta counter with a count efficiency of 53% and the CIso values are calculated using conventional statistical methods. The ability of the NK-1 receptor antagonists used in the methods of this invention to inhibit the proliferation of small cell lung carcinoma cells can be determined using the in vivo and in vitro cell proliferation assays described by Otrosz et al. ., International Journal of Cancer, .1.995, 6Q_, 82-87 and by Bunn et al., Cancer Research, 1994, 54, 3602-3610.

Claims

neither NOVELTY OF THE INVENTION CLAIMS I ..- To treat the nee on a mam forum, an NK-1 receptor antagonist that is: (a) a co-formula wherein A is a ring system selected from phenyl, naphthyl, thienyl, dihydroquinolinyl, quinolinyl and .indolinyl, and wherein the side chain containing NR2R3 is attached to a carbon atom of the ring system A; AA is an aryium group selected from phenyl, naphthyl, thienyl, quinolinyl, dihydroquinoline and indolinyl, and wherein the side chain containing NR-R3 is attached to a carbon atom of AA; AAA is an aryl group selected from phenyl, naphthyl, thienyl, quinolinyl, dihydroquinoline and indolinyl, and wherein the side chain -CH2 PR3 is attached to a carbon atom of the AAA ring; P is NR2, O, S, SO or SO2; 0 is SO2, NN, -Nalkyl C1-C-6) or (C1-Ce alkyl) -N-S02-, wherein the point of attachment of said (C 1 -C 4 alkyl) -N-SO 2 - to the ring AAA is the nitrogen atom and the point of attachment of X 5 is the sulfur atom; W- and are independently selected from hydrogen, halo, alkyl (Ci-Cß), S-alkyl Ci-C3) and alkoxy (Ci-Cg) optionally substituted with one to three fluorine atoms; W is hydrogen, an alkyl (Ci-Cß) optionally substituted with from one to three fluorine atoms. -S (0) y-alkyl (Ci-Cß) wherein v is zero, one or two, halo or an alkoxy (Ci-Ce) optionally substituted with one or three fluorine atoms; ? i is hydrogen, a (C1-C10) alkoxy optionally substituted with one to three fluorine atoms, or a (C1-C10) alkyl substituted opaquely with from one to three volumes of fluorine; X2 and 33 are independently selected from hydrogen, halo, nitro, (C1-C10) alkyl substituted by one to three fluorine atoms, alkoxy (Ci-C ?o) optionally substituted by one to three fluorine atoms, hydroxyl, phenol, cyano, amino, alkylamino (Ci-Cß), a dialkylaniline (Ci-Cß), -CÍO) -NH-alkyl (Ci-Cß), (alciuyl Ci-C) -C (0) - NH-alkyl (C? -C &), hydroxyalkyl (C1-C4), alkoxy (Ci-C) -alkyl (C? -C "), -NHC (0) H, and -NHC (0) - alkyl (Ca-C6); X5 is a four to six membered heterocyclic ring, containing from one to four heteroatoms selected from sulfur, nitrogen and oxygen (eg, thiazolyl, pyrrolethylo, thienyl, tpazolyl, tetrazolyl, oxazolyl, oxadiazolyl, thiadiazolyl or imidazole) 1I0), they see that said reterocyclic ring can optionally be substituted with one to three substituents, preferably from zero to two substituents, independently selected from phenyl, alkyl (Ci-Cß) substituted opaquely with one to three fluorine atoms. -, (Ci-Cβ) alkoxy optionally substituted with one to three fluorine and halo atoms; R is a 4-, 5- or 6-membered heterocyclic ring, containing one to four heteroatoms selected from oxygen, sulfur and nitrogen (eg, thiazolyl, azetidinyl, pyrrolyl, pyrazolyl, 1,2,3-trololyl) , 1, 2, 4 - 1, pacolyl, isothiazole 1, and irnidazolium, isoxazolyl, or oxazolyl), wherein said heterocyclic ring may contain from zero to three double bonds, and may be optionally substituted with one or more substituents, preferably one to two substituents, independently selected from an alkyl; (Ci-Cβ) optionally substituted with one to three fluorine atoms and an alkoxy (Ci-Ce) optionally substituted with one to three fluorine atoms; R1 is selected from amine, alkylamino (Ci-Cß), dialkylamino (Ci-Cß), -S (0) -acyl (C1-C10) / wherein v is zero, one or two, -S (0 ) v - eni.lo, where v is zero, one or two, -S (0) w -benzyl, where v is zero, one or two, -0-phenyl, - -0-benzyl, - S02 R R5, in which R * and RS each is, independently, an alkyl (Ci-Cß), or R * and RS, together with the nitrogen to which they are attached, form a saturated ring containing a nitrogen and three to six carbons, I -NHC (0) -alquÍl? (C? ~ C6), -NHC (0) CF3, (Ci-Cio alkyl) -N-SO2 - (C1-C10 alkyl), wherein neither or both of the alkyl radicals may be optionally substituted with one to three fluorine atoms, -N (S? 2 -alkyl C? -C? o) -2, (Ci-Cio alkyl) -N-S02-phenyl and (C1-C10 alkyl) -N-S? 2-benzyl; and wherein any of the phenyl radicals of the above Rl groups may be optionally substituted with one to three sustiuyent.es independently selected from a (C1-C4) alkyl, an alkoxy (C? ~ C_i) and halo; or R1 is a group that has the formula where a is 0, lo 2 and the asterisk represents a link to a meta position with respect to the side chain R R3 CH2; dotted lines of formula Ib represent that one of the links X-Y and Y-Z may optionally be a double bond; X is selected from -CH-, -CH2-, -0-, -S-, -SO-, -S02-, -N (R «) -, -NH-, ~ N-, -CHCalkyl (C? ~ Cß) 3-, -cCalkyl (Ci-Cß)] -, -CH (C 6 Hs) - y = C (C-6H-5) -; Y is selected from C ~ -0, C = NR *, C = S, -CH-, -CH2-, = CCalkyl (C? -C6) 3-, -CHCalkyl (Ci-Cß)] -, = C ( C6Hs) -, -C (C6H5) -, = N-, -NH-, -N (R *) -, = C (halo) -, = C0R *) -, = CISR *) -, = C (NR *), -0-, -S-, and SO2, in which the phenyl radicals (ie said -CICßHs) - and -CH (C6Hs) ~ may be optionally substituted with one to three sutituents independently selected from trifluoromethyl and halo, and wherein the alkyl radicals of said -CCalkyl (C? -Cβ) 3 and -CHCalkyl (C? -C6) 3- may optionally be substituted with one to three fluorine atoms; Z is selected from = CH-, -CH2-, = N-, -NH-, ~ S ~, -N (R *) -, -CICβHs) -, -CHICßHs) -, -CCalkyl CCi-Cß)] - V -CHCalkyl (C? -C6) 3 ~; or X, Y and Z, together with the two carbon atoms shared between the benzo ring and the XYZ ring, form a ring of condensed pyrimidine or priridine; R * is an alkyl (Ci-Cß) or phenyl, and each occurrence of R * ee independent of other occurrences of R * in the same molecule; R is hydrogen or a -C02alkyl (C? ~ C10); R3 is selected between VI VII IX VI 11 wherein R6 and R10 are independently selected from fupol, thienyl, pipdyl, mdolyl, bifelm and phenyl, wherein said phenyl may optionally be substituted with one or two substituents independently selected from halo, an alkyl (Ci- Cio) optionally substituted with one to three fluorine atoms, an alkoxy (Ci-Cio) optionally substituted with one to three fluorine, carboxyl, benzyloxycarbonyl and (C 1 -C 3) alkoxycarbonyl; R7", e selects between alkyls (03-0) branched, branched (C5-Cß) alkenyls, cycloalk (C3-C7) and the radicals mentioned in the definition of Rβ; Rβ is hydrogen or an alkyl (C) Cß): R9 and R10 are independently selected from phenyl, bifidoyl, naphthyl, pyridyl, benzhydryl, thienyl and furyl, and R9 and R10 may be optionally substituted with one to three scripts independently selected from halo, a (C1-C10) alkyl optionally substituted with one to three fluorine atoms and a (C1-C10) alkoxy optionally having one to three fluorine atoms; Yi is (CH2)? wherein 1 is an integer one to three, or? i is a group of formula 3 Zi is oxygen, sulfur, aryl, alkylamino (C1-C3) or (CH2) en where it is zero, one or two; x is an integer from zero to four; and is an integer from zero to four; z is an integer from one to six, in which the ring containing (CH2)? Can it contain from zero to three double bonds and one of the carbons of (CH2)? it can be optionally replaced by oxygen, sulfur or nitrogen; or it is two or three; p is zero or one; r ee one, two or three; R11 is thienyl, biphenyl or phenyl optionally substituted with one or two substituents independently selected from halo, a (C1-C10) alkyl optionally substituted with one to three fluorine atoms and a (C1-C10) alkoxy optionally substituted with one or three fluorine atoms; * is (CH2) q in which q is an integer of 1 6, and in which any one of the simple carbon-carbon bonds in said (CH2) may be optionally replaced by a carbon-carbon double bond, and in the that any one of the carbon atoms of said (CH2) q may be optionally substituted with Ri *, and wherein any one of the carbon atoms of said (CH2) q may be optionally substituted with Ris; m is an integer from 0 to 8, and any one of the simple carbon-carbon bonds of (CH2) -, in which both carbon atoms are bonded together, and to another carbon atom in the chain (CH2) - , it may optionally be replaced by a carbon-carbon double bond a carbon-carbon triple bond, and wherein any one of the carbon atoms of said (CH2) m having the required binding sites required may be optionally substituted with Ri. - Ri2 Ts a radical selected from hydrogen, a straight or branched alkyl (Ci-Cß), a (C3-C7) cycloalkyl, wherein one of the carbon atoms may be optionally replaced by nitrogen, oxygen or sulfur; an aryl selected from biphenyl, oxygen or sulfur; an aryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; (C2-C6) alkyl phenyl, benzhydryl and benzyl, wherein the point of attachment at R is a carbon atom except that Ri2 < is hydrogen, and wherein each of said aryl and heteroaryl groups and the phenyl radicals of said benzyl, (C2-C6) alkyl and benzhydryl may be optionally substituted with one or more substituents independently selected from halo, nitro, a (C 1 -C 10) alkyl optionally substituted with one to three fluorine atoms, an (C 1 -C 6) alkoxy optionally substituted with one to three fluorine, amino, hydroxyalkyl (Ci-Cß), alkoxy (Ci-) atoms; Cé) alkyl (Ci-Cß), alkylamino (Ci-Cß), (Ci-Cß alkyl) -QC (O) -, (Ci-Ce alkyl) -O- (0) - (Ci-C e alkyl), ( Ci-C-alkyl) - (0) -C (0) - (Ci-Cß alkyl) -, dialkylaryn. (Ci-Cß), -C- (0) NH- (Ci-Cß-alkyi), (Ci-alkyl) -Ce) ~ C (0) -NH- (Ci-Ce alkyl), -NHC (0) H and -NHC (O) - (Ci-Cß alkyl); and wherein one of the phenyl radicals of said benzhydryl may be optionally replaced by naphthyl, thienyl, furyl or pyridyl; R 3 is hydrogen, phenyl or alkyl (Ci-Cß); or R12 and R13 t together with the carbon to which they are attached, form a saturated carbocyclic ring having from 3 to 7 carbon atoms, in which one of said carbon atoms is not. the junction point of the spiro ring, or the one adjacent to it, may optionally be replaced by oxygen, nitrogen or sulfur; Rl * and Ris are each independently selected from hydrogen, hydroxyl, halo, amino, oxo (= 0 =, cyano, hydroxyalkyl, (Ci-Cß), alkoxy (Ci-Cß) alkyl (Ci-Cß), alkylamino (Ci-Cß), dialkylamino (Ci-Cß), alkoxy (Ci-Cß), ~ C (0) -0H, (Ci-C, 6-alkyl) -0-C (0) ~, (Ci-C6 alkyl) ) -0-0 (0) - (Ci-C alkyl), (Ci-Cd alkyl) -C (0) -0-, (Ci-Cß alkyl) -C (0) - (C? -C? Alkyl) ) -0-, (Ci-Cß alkyl) -C (0) -, (Ci-C- alkyl) -C (0) - (Ci-C-alkyl) - (Ci-Ce alkyl) -, and the radicals which they are defined in the definition R1; Rie is NHC (0) Ri-, NHCH2R18, SO2R18, GR20 CO2H or one of the radicals that are defined in any of the definitions of R12, Rl * and Ris; R1 is oximino (= N0H ) or one of the radicals which are defined in any of the "ef? icions of Ri2, Rl * and RiS; Rie is alkyl (Ci-Cß), hydrogen, phenyl or alkylphenyl (Ci-Cß); group consisting of CH2, nitrogen, oxygen, sulfur and carbonyl, R20 is a heterocyclic or bi-heterocycle cyclic selected from the group consisting of pyrinidinyl, benzoxazolyl, 2,3-dihydro-oxo-benzoisosul-fonazol-2-yl, rnorfolin-1-yl, thiolin-1-yl, benzofuranyl, benzothienyl, indolyl, isoindolyl, isoquinolinyl, furyl , pyridyl, isothiazolyl, oxazolyl, triazolyl, tetrazolyl, quinolyl, thiazolyl, thienyl and the groups of formulas wherein B and D are selected from carbon, oxygen and nitrogen, and B and D at least one is other than carbon; E is carbon or nitrogen; n is an integer "Je 1 to 5 and any of the carbons of (Cl-b) not (CH2) n +?, may optionally be substituted with an alkyl (Ci-Cß) or a spiroalkyl (C2-C6) and either a pair of carbon atoms of said (CH2) ny (CH2) n +? can a bridge be formed by a union of one or doe carbon atoms, or any pair of adjacent carbon atoms of said (CH2) n and (CH2) n +? can form, together with one to three carbon atoms that are not part of the ring containing the carbonyl, a fused carbocyclic ring (C3-C5); with the proviso that (a) when m is 0, of Ris and R 7 one is absent and the other is hydrogen, (b) when R3 is a group of formula VIII, R1 * and R15, together with the carbon atom To which they are attached, they form a saturated carbon dioxide ring (C3 -Ce), which forms a spiro compound with the ring containing the nitrogen to which they are attached; (d) R 2 and R 3, can not be * the two hydrogen, (e) when R 1 * or R s is bonded to a carbon atom of X * of group VII or to a carbon atom of (CH 2) and group VIII adjacent to the nitrogen atom of the ring, then Rl * or Ris, respectively, must be a substituent in which the point of attachment is a carbon atom; (f) when said compound is a group of formula Id or a group "je formula le or le, in which AA or AAA, respectively, is phenyl optionally substituted with 1, 2 or 3 groups selected from alkyl (Ci-Cß) , tpfluoromet ilo, halo, cyano, nitro, alkoxy (Ci-Cß), trifluoromethoxy and -S (0) v -alkyl (Ci-Cß), where v is zero, one or two and R3 is a group formula VII, in which Ri3 is hydrogen and R12 is phenyl, naphthyl, thienyl, furyl, piphod, thiazolyl, tetrazolyl, "jumolyl, benzhidplo or benzyl, and R12 is optionally substituted with alkyl (Ci-Cß), trifluoromet iio, alkoxy (Ci-Cß) or halo, then, at least one of Ri * and Ris must be different from hydrogen, alkyl (Ci-Cß), oxo, halo, -COOH, -C00 (alkyl (Ci-Cß), halo ot rifluoromethyl, and (g) nor Rl *, Ris, Rie or R1 can form a ring with RI3, or a pharmaceutically acceptable salt of said compound, or (b) a compound of formula wherein W is Y or X (CH2) n, Y is an optionally substituted (Ci-C6) alkyl, an optionally substituted (C2 -Ce) alkerule or optionally substituted C3-C3 cycloalkyl; X is an alkoxy ( Ci-Ce) optionally, hydroxyl, C0NR1R2, CO2R1, CHR1NR2R3, CORI, CONRi OR2, or an optionally substituted aplo, wherein said aplo is selected from femlo, naphthyl, pyridyl, quinola, thienyl, furyl, phenoxy phenyl, oxazolyl, tetrazolyl, thiazolyl, irnidazolyl, and pyrazolyl, and n is an enter * or zero to six, Ar-i, Ar2 and Ar3 are each independently, optionally substituted, in which it is selected from femyl, naphthyl, pipdyl, quinilyl, thienyl, furyl, phenoxyphenyl, oxazolyl, tetrazolyl, thiazolyl, imidazolyl and pyrazolyl, and R 1, R 2 and R 3 are independently selected from hydrogen, substituted (Ci-Cß) alkyl optionally, lcoxyl (Ci-Ce) optionally substituted, a cycloalkyl (C3-Cß) substituted option ally, optionally substituted aryl, wherein said alkyl is selected from femlo, naphthyl, pyridium, qumolyl, thienyl, furyl, phenoxy phenyl, oxazolyl, tetrazolyl, thiazolyl, irnidazolyl, pyrazolyl; and optionally substituted heterocyclic groups (C3 ~ Cs), wherein said heterocyclic groups are selected from pyrrolidino, pipepdmo, rnorfolmo, piperazinyl, t-nornorfolino; and wherein the substituents of the preceding alkyl, alkenyl, cycloalkyl and alkoxy groups are independently selected from halo, nitro, amino, (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy, trifluoromethyl and tp luorornetoxyl; and wherein the substituents of the preceding (C3-C5) heterocyclic groups are attached to the sulfur or ring nitrogen atom and are independently selected from oxygen, dioxygen and (C1-C4) alkyl when attached to the volume of sulfur ring, and are independently selected from oxygen, and alkyl (Ci-C ^) when they are attached to the ring nitrogen atom; and in the < } The substituents of said substituted Ar groups are independently selected from (Ci-Cß) alkyl optionally substituted with one to three halo groups, alkylsulfini lo (Ci-Cß), alken.lo (C2 ~ Ce), thioalkyl (Ci-). Cß), alkylsulfonyl (Ci-Cß), alkylsui foni lamino (Ci-Cß) and dialkylamino (Ci-Ce), in which one of the two groups alsulullo (Ci-Ce) or an alkylsulfini (Ci- Cß); and wherein the substituents of the substituted Ar2 and Ar3 groups mentioned are independently selected from (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) thioalkyl, to uilsulfinyl (Ci-C ^) ), dialkylamino (Ci-Ci,), trifluororneti lo yt pfluorornetoxyl; with the proviso that when Y is not substituted or substituted by an alkyl (CI-CÜ), it is attached to position 4 or 6 of the qumuclidine ring; or a pharmaceutically acceptable salt of said compound; or (c) a compound of formula xv i p wherein Ari and Ar2 are each, independently, thienyl, phenyl, fluorophenyl, chlorophenyl or bromophenyl; X is -C0NR3R *, -CO2R3, -CH2OR3, -CH2NR3R * or -C0NR30R *; R1, R3 and R * are each, independently, hydrogen or an alkyl having 1 to 4 carbon atoms; R2 is an alkyl having 1 to 4 carbon atoms; And it is an alkylsul onyl having from 1 to 4 carbon atoms, an N-alkyl-N-alkanoylamino (which may be substituted with a halogen in the alkanoyl radical), having from 1 to 4 carbon atoms in the alkyl radicals and alkanoyl, an N-alkyl- N -alkylsufoni.lami.no (which may be substituted with a halogen in the alkylsulfonyl radical), having from 1 to 4 carbon atoms in the alkyl and alkylsulfonyl radicals, an alkenyl having 2 to 4 carbon atoms, an alkynyl having 2 to 4 carbon atoms, an alkylamino having 1 to 4 carbon atoms, an alkanoylamino (which may be substituted with a halogen) having 1 to 4 carbon atoms, carbon or an alkyl Isulfomlamino (which may be substituted with a halogen) having 1 to 4 carbon atoms; or a pharmaceutically acceptable salt of said compound; or (d) a compound of formula XVII in which Ar and Ar2 are each independently an aplo or a substituted aryl; R1 is an alkyl having 1 to 6 carbon atoms; R 2 is hydrogen or an alkyl having 1 to 6 carbon atoms; and well, X and Y are separately broken and each is, independently, hydrogen, dialkylphosphoyl having 2 to 12 carbon atoms, an alkyl having 6 carbon atoms, alkyloxy having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or alkynyl having 2 to 6 carbon atoms; or X and Y are taken together and represent a hydrocarbon chain having 3, 4 or 5 carbon atoms, optionally containing up to two bond bonds and optionally having 1 or 2 substituents selected from oxo, hydroxyl and an alkyl having 1 to 6 carbon atoms; with the condition that when X and Y are taken together they are attached to adjacent carbon atoms; and with the proviso that, if X or Y is hydrogen, then the other must be alkenyl or alkynyl; or a pharmaceutically acceptable salt of said compound; or (e) a compound of formula XIX wherein R is an alkyl (Ci-Cß); X is an alkyl (C? ~ Ce) having one or more substituents linked through a heteroatom; Ar-i and r2 are each, independently, an aryl optionally substituted by an alkyl (Ci-Cß), alkoxy (Ci-Ce), thioalkyl (Ci-Ce), halogen, cyano, nitro, phenoxy, mono-Ikylamino (Ci-Cé), dialkylamino (Ci-Cß), a halosubstituted alkyl (C? ~ Ce) or haloxyl (Ci-Cß) halosubstituted; Y is hydrogen, an alkyl (Ci-Cß), an alkenyl (C2-Ce), a cycloalkyl (C3-C8), a Z- (CH2) P ~, or a W- (CH2) m ~ CHR2 - (CH2 ) n -NRiCO- wherein Y is in the 4-, 5- or 6- position of the quinuclidine ring; Ri is hydrogen, an alkyl (Ci-C,), benzyl or - (CH 2) r- W; R 2 is hydrogen or (C 1 -C 6) alkyl which may be substituted by a hydroxyl, amino, thiomethyl, mercapto, benzyl, 4-hydroxybenzyl, 3-indolyl-phenyl or a - (CH 2) r-W; Z is an alkoxy (Ci-Ce), -C0NR * RS, -C02R *, ~ CHR * 0R5, -CHR * NRSR6-COR *, ~ C0NR * 0RS or a substitute aryl < Jo optionally; each W is independently cyano, hydroxymethyl, (C2-C6) alkoxymethyl, aminornetyl, rnonoalkyl (Ci-Cβ) aminornetyl, diacyl (Ci-Cg) arninomethyl, carboxyl, carbamoyl or alkoxycarbonyl (Ci-Cß); R *, RS and RS are independently hydrogen, alkyl (Ci-Cß), alkoxy (Ci-Ce), a (C3-C8) cycloalkyl or a group Heterocyclic or optionally substituted aryl; p is 0 to 6; and m, n and r are each, independently, from 0 to 3; or a pharmaceutically acceptable salt of said compound; or (f) a compound of formula XX wherein X and Y are each hydrogen, halo, alkyl (Ci-Ce), halo (Ci-Cß) halo substituted, alkoxy (Ci-Cß), thioalkyl (C? ~ ? Ce), alkylsulfinyl (Ci-Cß), alkylsulfonyl (Ci-Ce), or trialkylsilyl (Ci-Cß); Ari and Ar2 are each an aryl optionally substituted by halo; A is -CO- or (CH2) -; Z-A - is in the 5 0 6 position of the qumuclidine ring; Z is hydroxy, alkoxy (Ci-Ce), NR1R2 or - (CH2) - -CHR * - (CH2) n ~ NR3, wherein R1 and R2, when taken separately, are each hydrogen or a alkyl (Ci-Cß); R1 and R2, when taken together with the nitrogen atom to which they are attached, represent pipepdmo, pyrrolid, morpholino, t ororpholino or piperazino; R 3 is hydrogen, alkyl (Ci-Cß), benzyl or - (CH 2) r ~ W 2; R * is hydrogen or an alkyl (C? ~ Ce9 which may be substituted by hydroxyl, ammo, thiomethyl, mercapto, benzyl, 4-hydroxybenzyl, 3-? Ndol? Lmeth or - (CH2) »~ W3; R3 and R *, when taken together, represent CH2 or CH2CH2;, W2 and W3 are each cyano, hydroxymethyl, alkoxymethyl (C2-Ce), arninometiio, methyl (alkylamino Ci-C), methyl (dialkylamino Ci-C), carboxyl , carbamoyl (C 1 -C 69 alkyl, or carbamoyl 1 'dialkyl Ci -Ce), carbamoyl or car-boml (Ci-Cβ alkoxy), and m, n, rys are each 0, 1, 2 or 3; pharmaceutically acceptable "Jicho compound; or (g) a compound" je formula XX! wherein Y is an alkylene (C2-C4) Z is a valence bond or an alkylene (Ci-Cß); R1 is phenyl, biphenyl, indanyl, naphthyl, thienyl, fuplo, pyr-idyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, tetrazole 1, quinolyl, alkyl (Ci-O) phenyl or benzhidplo, wherein each of the radicals of the ring can be optionally substituted by one or more substitutes selected independently from halogen, alkyl (Ci-Ce), alkyl (Ci-Cß) halosuted, alkoxy (Ci-C) and alkoxy (Ci-Cβ) halosubstituted; R2 is hydrogen or an alkyl (Ci-Cß); R3 is hydrogen, hydroxyl, cyano, arnino or carboxyl; and R * represents a group of formula XXII or XXIII XXI I XXI I I wherein XI, X2 and X3 are each, independently, halo, hydrogen, nitro, alkyl (Ci-Ce), alkoxy (Ci-Cß), alkyl (Ci-Cß) halosubstituted, alkoxy (Ci-Cé) halo-substituted, hydroxy, amino, thioalkyl (C-C), alkylsul fonyl (Ci-Cß) or alkyl sulfomyl (Ci-Ce); O1 and O2 are each H2, oxygen or sulfur; A is a bond of valence, rnetylene, oxygen, sulfur or NH; RS and R6 are each hydrogen or alkyl (Ci-Cß); and R7 or hydrogen, halogen, alkyl (Ci-C) halosubstituted (Ci-Cß) alkyl or alkoxy (Ci-Cß); with the proviso that when Z is a valence bond, R3 must be hydrogen; or a pharmaceutically acceptable salt of said compound, in the preparation of compositions.
2. The use of a compound according to claim 1, wherein the cancer being treated is a small cell lung carcinoma.
3. The use of a compound according to claim 1, wherein the cancer being treated is an extrapulmonary small cell carcinoma.
4. The use of a compound according to claim 1, wherein the cancer being treated is a turnor neuroendocp no.
5. The use of a compound according to claim 1, wherein the cancer being treated is an astrocytoma.
6. The use of a compound according to claim 1, wherein the cancer "treated" is APUDorna.
7. The use of a compound according to claim 1, wherein the NK-1 receptor antagonist used is selected from the group consisting of: (25,35) -3- (5-tert-butyl) 2-methox? Benc? L) a? No-2- (3-tpl uoromethoxyphene Dpi pendant; (2S, 3S) -3- (2-? Sopro? Ox? -5-t ri fluorometox? Benc? L) arn? o-2 ~ fen? lp? pepd? na; (2S, 3S) -3- (2-ethoxy -5-trif luoromet oxybenzeneDamino- 2-phenyl pipen dine; (25, 3S) -3- (2-rnetoxy-5-tri fluoromethoxybenzyl) arnino-2-f and i 1 pi pe ri di n; (2S, 3S) -3- (5-te -but-1 -2-tri fluoromethoxybenzyl) amino-2-phenylimidine; (2S, 3S) -3- (5-te re- but i.1-2 - 1 ri f 1 uo ro ethoxy benz 1) ami no - 2 - pheni 1 pi pe ri. di na; 2 - (di phenyltrnetii) -N- (2-methoxy-5-trifluo romethoxyl) phenyl) -rnet.yl -1-azabicyclo C2.2.23 octan-3-arnine; (2S, 3S) -3-C5-chloro-2- (2,2,2-trifluoroethoxy) benzyl-amino-2-phenyl-1-pyridine; (25, 3S) -3- (5-tert-Butyl-2-trifluoromethoxybenzyl) amy no-2-phenylpiperidyl; (2 S, 3 S) - 3- (2 - i sop ropox i - 5 -t ri f 1 u rometox i benci 1) arni no- 2 -f eni 1 pi pe ri di n; (2S, 3S) -3- (2-di f 1 or rornetox i -5 -tri fluoromethoxybenzyl) -amino-2-phenylpiperidine; (2S, 3S) -2-phenyl-3-C2- (2,2,2-trifluoroethoxybenzyl) 3-arninopiperidine; (2S, 35) -2- phenyl -3- (2-trif luo rometox i benci 1) -arni. nopi pe ri di na; c i s - 3 - (2 - c 1 or robenci lami no) - 2 - feni 1 pi pe r i di na; cis-3-t riflurornet i lbenc i larni no) -2- phenyl pipe ridine; cie-3-methoxy benzylami no -2- (2-flurophenyl) -piperidine; cis -3-rnetoxy benci lami no -2- (2-chloro phenyl) -piperidine; cis-3-methox ibenci larni no - 2 - (2-methox i f eni 1) - pi pe r i d i na; cis-3-rnetoxy benci larni no - 2 - (3 -rnetox i f in i.1) - pi pe ri di na; cis-3-rnetoxy benzy lami no -2- (3-fluoro phenyl) -piperidine; cis-3-methox. i benci lami or -2- (3-chloropheni 1) -piperidine; cis-3-rnetoxy. benzylamino 2 - pheni 1 pi pe ri di na; cis-3-methox i be n c i 1 m i no -2- (3-methyphenyl) -piperidine; cis-3-rnetoxy benc i larni no -2- (4-fluorophenyl) -piperidine; cis-3-methoxy-benzyl-lamino -2- (3-t.ienyl) piperidine; cis-3-rnetoxy benzylami-2-phenylazacycloheptane; 3-9- rnetoxybenzyl-cinnamino) -4-methyl-1 -2-phenylpiper idin; 3- (2-rnetox i benc i lamí no) - -met? L-2-phenyl pipen dina; 3- (2-ethoxy benzylamino) -6 ~ met? 1-2 -femlpí pepdina; (25, 3S) -1- (5 -carboetox? Pent-l-? L) -3- (2-rnetox ibencylamino) -2 -femlpipep di na; i 25, 35) -l- (6-hydroxy? hexyl) -3- (2-rnetoxybenzyl) -2 femyl piperidine; (2S, 3S) -l- (4-h? Drox? -4-phen? Lbut-1 -? L) -3- (2-methoxybenzylamino) -2-phenylpipepdine; (25, 3S) -1- (4-oxo-4-phenyl] -butyl-1-yl) -3- (2-methoxy-benzyl-lamino) -2-phenyl-p-pepd? na (2S, 3S) -1- (5,6-d? H? Drox? Hex- l ~? L) -3- (2-methoxy and benzyllar) -2-phenyl pipen dine; c? s-3- (5-fluoro-2-methoxy benei lam no) -2-phen? -pipen dine; (25, 35) -1- 4- (4-fluorophenyl) -4-oxobut-l-? L3-3- (2-rnetox? Benc? Larn? No) -2-phen? Lp? Epd? Na; (2S, 35) -1-C4 ~ (4 ~ fl uorof in 1) -4-h? Drox? But? -l-? L -3- (2-met oxybenzylamine) -2-phenylpipepdine; c? s ~ 3- (2-methox? ~ 5-met? lbenc? lamino) -2-phenylpiper-id na; (2S, 3S) ~ l- (4 ~ benzarn? Jo bu t ~ l-? L) -3 - (? - rneto x i benc i lamí no) -2-fen? Lp? Per? D? Na; c? s-3- (2-? netox? n ft-l-ílmet i lamino) -2- femlpí pendí na; (2S, 3S) -3- (2-r-methoxybenzylamino) -1- (5-N-meth? I-carboxarn? Dopent-1-? L) -2-phenylpipenia; (2S, 3S) -l- (4-c? Anobut-1-? L) -3- (2-methox? Benc? Lam? No) -2-phen? lpipendine; (25, 35) - 1 - C4 - (2-naphthamido) but-1-? 13 -3- (2-methox? Benc? Lam? No) -2-phen? Lp? Per? D? Na; (25,35) -1- (5-benzam? Dopent ~ l-? I) -3- (2-methox? Benc? Larn? No) -2-phenylpipendine; (2S, 3S) -1- (5-am? No? Ent-l-? L) -3- (2-rnetoxybenzylamino) -2 ~ phen? Lp? Pepd? Na, (2S, 3S) ~ 3- ( 5-chloro-2-methoxy? Benzyl? No) -2- femylpiperidine; (25,35) -? - (2,5-dimethoxybenzyl) -2-femlp? er? d? na; c? s-3- (3,5-di luoro -2-methox i be nci lamino) -2- fen? l pipen di na; c? s-3 - (4, 5 -di f luoro- 2 -rne to x i benc i lamino) -2- phenyl pi in di na; c? s-3- (2, 5-d irne t oxi benc i lamí no) -1-T4- (4-f luorofeml) -4-oxobut-l-? l32-ferulpí pendí na; c? s-3- (5-chloro-2-rne ox? benc? lam? o) -1- (5,6-dihydroxy hex-1-yl) -2-phenylpipepdine; c? s-1- (5,6-d? hi drox hex-y-il) -3- (2,5-d? rnet oxy-benzylamine) -2-phen? lp? per? dma; c? s-2-phen? l ~ 2-C2 - (? rop-2-? lox?) benc? larn? or - perid? na; c? s-3- (2,5-dirnetoxybenzyl) am? no-2- (3-methox? phenyl) -pipepdine; c? s-3- (5-chloro-2? -neurox? benc? l) am? no-2- (3-methox? fem) p? epd? na; c? s ~ (5-chloro-2-methoxy? benc?) am? no-2- (3-chlorophen? l) p? pepd? na; 3 - (2-methoxy ibenei lamino) -2, -d? Phen? Lp? Pepd? Na; c? s-3- (2-methox? benc? larn? no) -2-fen? lp? rrol? d? na; (2S, 3S) -3- (5-e? L-2-rne t or x i bencí 1) an i no- 2 - f eni 1 ?? pe p di na; (2S, 35) - 3 - (5-n-bu 111-2-methoxy-encyl) arn-no-2-phenylpiperion; (25.3S) - 3- (2 ~ rnetox? -5 ~ n-propylbenzyl) ammo-2-phenylpiperi na; (25, 3S) -3- (5-isopr-opy 1 -2-rnetoxybenzyl) a? N? No-2-phen? lpipep dina; (25, 35) -3- (5- s-butyl l-2-rnetoxybenzyl) amine-2-phenolipid "Ji na; (25, 3?) -3- (5-t-but? L-2-methoxybenzyl) am? No-2-phenylpipendma; (25, 35) -3- (2-methoxy? -5-i-enylbenzyl) am? No-2-phen? Lp? Pend? Na; C 4 -methoxy -3- ((25,35) -2- enyl pipepdin-3-ylammomethyl) fem l3rnet? Licking of 2,4-dirnet-ilthiazole-5-phonic acid; N- (4,5-d? Met? Lt? Azol-2-? L) -N-rne oxy -3 - ((25,3S) -2- phen il pipen din- - il-arninomethyl) phen? Lmetansul fonamide; . { 5-C (4, 5-d? Met? L t? Zol-2-il) rnet? lamino 3- 2 - rnetox i boncil} - ((25, 35) -2- phenyl pipen di n-3-yl) amine; C5 ~ (4, 5-d? Rnet? Lt? Azol-2? Larn? No) -2-methoxy and benc 11} - ((2S, 3S) -2-fen lp? Pepdin-3-? L) arn? Na; Met-C3- ((25,35) -2- fem l ??? er? dm-3- ilarninomet íl) ~ 4-tn f luoromethoxy feni 1 a? da-del > CJ do 4,5- di met j] t í zol - 2 - phonic cell; -? sopropox? -3- ((25,35) -2- phen? l? pend n-3-? lam? nomet?) fen? l3me «2,4-dunetyl taazole-5-ylonic acid iammine; 4-? Sopropox? -3- ((25, 35) - 2 -fen? Lp? Pepd? N-3-? Lam? Nomet?) Feni pisopropilanuda acid 2,4-di-met-111-azole-5-sulphonic acid; C 4 - methox i ~ 'l - ((2S, 3S) -2-fen? L ??? epd? N-3- lamí nornetii) fen? L3? Soprop? Larn? Na of aci do., 4-d ?? net j 1 t zol -5 -phonic lens; C4-? Netox? -3 - ((35,35) -2-femlp? Pepd? N-3- ilammomethyl) fen? L? Soprop? Lam? of the acid 2,4-d? rnet? lt? azol-5-sulfon? co; 4-rnetox? -3 ~ ((25, 35) -2- phen? L ??? end? N-3-? Lam? Nomet? I) feni 1 isobuty lamin of 2,4-dirnetylthiazole-5-sulfate acid unique C4- i sopro? Ox? ~ 3 - ((25, 35) - 2-femlp? Per? D? N-3-? Lam? Nomet? I) fen? Lisoiso? Iarn? Of acid 2.4 ~ d ? rnet? lt? azole-5-sulfon? co; (25, 3S) N- (5-? Soprop? 1-2-rethoxyphenyl) me? L-2-d? Phen? Lmet? I-azab? C? CloC2.2.23octan-3 -imine; (2S, 3S) -N- (5-tert-bu? 1-2 -ethoxy enyl) rnet? I-2 ~ < l? fen? lme? l-l -zab? c? cloC2.2.2. octan-3-amine; (25, 35) -N- (5-rneti 1-2-methoxy and feni 1) mef 11 -2-d? fenilrneti 1-1 -azab? c? loC2.2.23octan-3-arn? to; (25, 3?) ~ N- (5-et? L-2-rnetoxifeniDmetil-2-d? Fem lmet? Ll-azab? C? Clo 2.2.23 octan-3-amine; (25, 3S) -N - (5-? Soprop? L -2- etox i feml)? Net? L-2-d? Femlrnet? Ii-azab? C? Clo 2.2.23octan-3-arn? Na; (25,35) -N - (5-sec -but? L-2-methoxyfem) I put 1-2-di-phenyl-ethyl-1-azab? C? CloC2.2.23octan-3-arnine; (25, 3S) ~ N- (5-n ~? Rop? 1-2-methoxy-phen) 1) met? L- 2-di fen? Lne? Ii-azab? Cyclone.2.23 octan -3-amine; (25, 35) -2-di feni lmet? l -3- (5-tere-t > ut? 1 -2- ethoxybenzyl) am? no-l-azab? c? chlor2.2.23octan-3-arnine; (25, 35) -2 -di-phenylmethyl-1-3- (5-tert-butyl-1-2-methoxy-benzyl) -amino-1-azab-cclo 2.2.23octane; (25.3S) -N-C5- (1-c? Ano-l-rnet? Let? L) 2-rnetox? Benc? 3-2- phenyl pipen din-3-amine; (25, 35) -3- (6-methox? -l -met l-2-oxo-l, 2, 3,4-tetrahydroquinol-7-yl) rnet? l ~ 2-phen? lp? per? d? n-3-am? na; 2S, 3S) -2-phen? 1-N-C5-C2, 2, 2-tr? Fluo o-1 - (nf 1 uorornot 11) eta 13 - 2 -rne tox i bencí 11 pi pe pdi n- 3 - arní na; i 25, 3S) -2-d? forul -N- 2-methox? -5 - (m ílsul fonil) -benc? l3- l-azabici cio 2.2.23 octan-3-amine; (25,35) -2-d? Fen? lmethyl-N- (5 -propropenyl-2-mektoxy? benc? 3-l-azab? c? cloC2.2.23octan-3-amine; (25,35) -2-d? Phen? Lmet? LN-C5- (lh? Drox? -l-me? Let? L) -2-methox? Benc? L3-l-azab? C? Clo 2.2. 23 octan -amine; (3R, 45, 55.65) -N, N-d? Et? l-5- (5-? soprop? l-2- rnetox? -benc? lam? no) -6-d? in? -rnethyl-1-azab? c? clo 2.2.23octan-3-carboxam? d; (3R, 4SA, 5S, 65) -N, N- "J? Et? I-5- (2, 5-d? Rnetox? Benc? Lam? No) -6-d? Phen? Lmet? I-? - zabici cío C .2.2 ocf an-3-c -boxam? to; acid (3R, 45, 55, 65) -5- (5-isopropyl-2-rnetox? benc? l-am? no) -6-d? phen? Jmeta 1 - 1 -azab? C? CloC2.2.23octan-3 ~ car-box? L? Co; acid (3R, 45, 55, 65) -5- (2-methoxy-2-met? it? obenc? l-am? no) -6-d? phen lrnet? ll-azab? c? cloC2.2.23octan -3-carboxyl? Co; acid (R, 45, 5S, 65) -5- (2, 5-d? rnetox? benc? lam? no) -6-difenilrnetii -? - azab? c? clo 2.2.23octan-3-carbox? l? co; acid (3R, 5,55,5) ~ 5 - (2 rnetoxy-5-met? ibenc? lam? no) -6-d? fem l? net? i-1-azab? c? loC2.2.23octan- 3-carboxyl; acid (3R, 45.55.65) ~ 5 ~ (5-ethyl-2-rnetoxy? benc? lam? no) -6-diphenylrnenyl-1-azab? c? cloC2.2.23 octane-3-carboxyl? co; ac? «jo (3R, 45,55, 65) -5- (2-methoxy-5-n-propylbonc lam mo) -6-d? phenyl and l-1-cyzab? cycloC2.2.2 oct an-3-carbo? lico, - acid (3R, 45, 55,65) - 5- (-sec-but? l-2-methox? benc? la ? n? no) -6-d? fen? l? net i- -azabiei cío [2.2.23 octan-3-carboxylic; acid (3R, 45.55.65) -5- (5- sec -butii -2-rnetox? benzylamino) -6 -difem l and 11 -l -zab? cicloC2.2.23octan-3-car * boxíl? co; (3R, 45,55,65) -5- (5 ~ N-rnet? i-methanesulfon? lam? no-2-methox? benc? lamino) -6-diphenylmethyl-1-azab? c? 2.2.23octan-3-carboxylic; aci do (3R, 45.55.6S) -5- (2-rnetox? -5-? net? lsulfin? 1bencilami o) -6 -difenilmeti i-a-azabicyclo C2.2.23 octan-3-carboxy 1 ico; acid (3R, 45.5S, 65) -5- (2-methox? -5-tp fluoromethoxybenzylamino) -6-d? phen? lmethyl-1-azabicyclo? 2 .2.2.23octane-3-carboxylic acid; acid (3R, 45.5S, 6S) -5- (2-methox? -5-methylsulfomylbenzamino) -6-di enylmet l-l-azab? c? clo 2.2.23octane-3-carboxylic acid; ci do (3R, 4S, 55.6S) -5- (5-d? met? lam? o-2-methox benzylamino) -6-di femmethyl? l-azab? c? cloC2.2.23octan-3 - carboxyl ico; acid (3R, 45, 55, 65) -5- (5-? so? rop? l-2-ethoxybenzyl lamino) 6-d? phen? lmet? i ~ l-azabic? cloC2.2.23octan-2-carboxyl ?co; (3R, 45, 55, 6S) -5- (2-rnetoxy-5-rnot? lthiobenz? lamino) -6-diphenyl eti i-azabic? cloC2.2.23 octane-2-carboxylic acid; acid (3R, 4S, 5S, 6S) -5- (5-? soprop? l -2-mefox ibencylamine) -6-diphenol l-l-azab? c? clo 2.2.23octan-2-carboxyl? co; Acid (3R, 4S, 5S, 6S) -5- (2-methox? -5-met? lt? obenc? lam? no) -6-di femlmet ll ~ azab? c? cloC2.2.23octan- 2 - carboxylic; ac do (3R, 45,55,65) -5- (2,5-d? metox? benc? lam? no) -6 ~ «l? fem lrnet? l-1 -azab? cycleC2.2.2? Ctan- 2-carboxyl ico; acid (3R, 45, 55, 65) -5- (2-methoxy-5-methyl-1-benzylamine) - 6-di f eni lrnet i 1- 1 -azabi cy 2.2.2 octan- 2 - carboxylic acid; (3R, 4S, 5S, 65) -5- (5-et i 1-2 -rnetoxy benzylamine) - 6 - di f eni lrnet i 1 - 1 -azabicycloC2.2.23octan-2-carboxylic acid; acid (3R, 4S, 55, 65) -5- (2-rnetox i-5-n- p ropi.1 benc i 1 ami no) - 6 - di feni 1 met i 1 - 1 -azabici.cloC2.2.23 octane-2-carboxylic; Acid «Jo (34, 45, 5S, 6S) -5- (5-sec-butyl-methoxy-benzyl-amino) -6-di-pheni-lrneti-1-1-azabiciclo 2.2.2.3octane-2-carboxylic acid; (3R, 45, 5S, 6S) -5- (5-N-rnetiirnetanosui.lamino-2-methoxybenzilarnino) -6-diphenylmethyl-1-azabicycloC2.2.23 octane-2-carboxylic acid; (3R, 5, 55, 6S) -5- (2-rnetoxy-5-? net.i.lsulfinylbenzyl) amino) -6-diphenylmethyl-1-azabicycloC2.2.23 octane-2-carboxylic acid; (3R, 4S, 5S, 65) - 5 - (2-rnetoxy-5-tri fluoromethoxybenzyl) nyl) -6-di-phenylneti-1-azabicycloC2.2.23octane-2-carboxylic acid; and (3R, 45, 55, 6S) - -5- (5-di rnet i..larni no- 2 -rnetox i benci lami) - 6 - di f eni Irnet i 1 - 1 -azabicycloC2.2.23octan ~ 2-carboxyl.ico; and the pharmaceutically acceptable salts of the above compounds.