Aza hydroxylated ethyl amine compounds

A compound of the formula III:

• or a pharmaceutically acceptable salt thereof wherein
• R1 represents phenyl (C1-C6)alkyl where the phenyl is optionally substituted with up to three groups independently selected from halogen, hydroxy, C1-C2 alkyl, C1-C2 alkoxy, amino, nitro, trifluoromethyl, cyano, mono(C1-C2)alkylamino and di(C1-C2)alkylamino;
• Ra and Rb independently represent hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C6)alkyl, C3-C7 cycloalkyl(C1-C6)alkoxy, halogen, cyano, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, mono- or di(C1-C6)alkylaminosulfonyl, C1-C6 alkyl sulfonylamino, C2-C6 alkenyl, C2-C6 alkynyl, trifluoromethyl, mono(C1-C6)alkylaminocarbonyl, or di(C1-C6)alkylaminocarbonyl and provided that not both Ra and Rb are hydrogen simultaneously;
• Rc represents hydrogen, or C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl each of which is optionally substituted with halogen, hydroxy, amino, cyano, or trifluoromethyl;
• Rd represents
• phenyl optionally substituted with hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C6)alkyl, C3-C7 cycloalkyl(C1-C6)alkoxy, halogen, cyano, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, mono- or di(C1-C6)alkylaminosulfonyl, C1-C6 alkyl sulfonylamino, C2-C6 alkenyl, C2-C6 alkynyl;
• or
• C1-C6 alkyl optionally substituted with hydroxy, C1-C6 alkyl, C1-C6 alkoxy, halogen, cyano, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, or trifluoromethyl;
• and
• R20 represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or trifluoromethyl.

A compound of the formula V:

• or a pharmaceutically acceptable salt thereof wherein
• R1 represents phenyl (C1-C6)alkyl where the phenyl is optionally substituted with up to three groups independently selected from halogen, hydroxy, C1-C2 alkyl, C1-C2 alkoxy, amino, nitro, trifluoromethyl, cyano, mono(C1-C2)alkylamino and di(C1-C2)alkylamino;
• Ra and Rb independently represent hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C6)alkyl, C3-C7 cycloalkyl(C1-C6)alkoxy, halogen, cyano, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, mono- or di(C1-C6)alkylaminosulfonyl, C1-C6 alkyl sulfonylamino, C2-C6 alkenyl, C2-C6 alkynyl, trifluoromethyl, mono(C1-C6)alkylaminocarbonyl, or di(C1-C6)alkylaminocarbonyl and provided that not both Ra and Rb are hydrogen simultaneously;
• Rc represents hydrogen, or C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl each of which is optionally substituted with halogen, hydroxy, amino, cyano, or trifluoromethyl;
• Rd represents
• phenyl optionally substituted with hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C6)alkyl, C3-C7 cycloalkyl(C1-C6)alkoxy, halogen, cyano, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, mono- or di(C1-C6)alkylaminosulfonyl, C1-C6 alkyl sulfonylamino, C2-C6 alkenyl, C2-C6 alkynyl;
• or
• C1-C6 alkyl optionally substituted with hydroxy, C1-C6 alkyl, C1-C6 alkoxy, halogen, cyano, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, or trifluoromethyl;
• and
• R20 represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or trifluoromethyl.

A method of treating a patient who has, or in preventing a patient from getting, a disease or condition selected from the group consisting of Alzheimer's disease, for helping prevent or delay the onset of Alzheimer's disease, for treating patients with mild cognitive impairment (MCI) and preventing or delaying the onset of Alzheimer's disease in those who would progress from MCI to AD, for treating Down's syndrome, for treating humans who have Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treating cerebral amyloid angiopathy and preventing its potential consequences, i.e. single and recurrent lobar hemorrhages, for treating other degenerative dementias, including dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease and who is in need of such treatment which comprises administration of a therapeutically effective amount of a compound selected from the group consisting of an aza hydroxylated ethyl amine of the formula II:

• or a pharmaceutically acceptable salt thereof, where Rc is
• (I) —C1-C10 alkyl optionally substituted with one, two or three groups independently selected from the group consisting of C1-C3 alkyl, halogen, —OH, —SH, —C≡N, —CF3, C1-C6 alkoxy, —O—phenyl, —NR1-aR1-b, —OC═O NR1-aR1-b, —S(═O)0-2 R1-a, —NR1-aC═O NR1-aR1-b, —C═O NR1-aR1-b, and —S(═O)2 NR1-aR1-b wherein
• R1-a and R1-b at each occurrence are independently H or C1-C6 alkyl,
• (II) —(CH2)0-3—(C3-C8)cycloalkyl where cycloalkyl can be optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, halogen, —OH, —SH, —C≡N, —CF3, C1-C6 alkoxy, —O-phenyl, —CO2H, —CO2—(C1-C4 alkyl), and —NR1-aR1-b
• (III) —(CRC-xRC-y)0-4-RC-aryl where RC-x and RC-y are independently selected from the group consisting of
• —H,
• C1-C4 alkyl optionally substituted with 1 or 2 —OH,
• C1-C4 alkoxy optionally substituted with 1, 2, or 3 halogen,
• —(CH2)0-4—C3-C8 cycloalkyl,
• C2-C6 alkenyl containing one or two double bonds,
• C2-C6 alkynyl containing one or two triple bonds, and phenyl, or
• RC-x and RC-y are taken together with the carbon to which they are attached to form a carbocycle of three, four, five, six or seven carbon atoms, where one carbon atom is optionally replaced by a group selected from —O—, —S—, —SO2—, —NRN-2— and RC-aryl, wherein
• R2-aryl is phenyl, which is optionally substituted with 1, 2, or 3 groups that are independently:
• (1) C1-C6 alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C1-C3 alkyl, halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (2) —OH,
• (3) —NO2,
• (4) halogen,
• (5) —CO2H,
• (6) —C≡N,
• (7) —(CH2)0-4—CO—NRN-2RN-3 where
• RN-2 and RN-3 are independently selected from the group consisting of:
• (a) —H,
• (b) —C1-C6 alkyl optionally substituted with one substituent selected from the group consisting of:
• (i) —OH, and
• (ii) —NH2,
• (c) —C1-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —Br, —I, or OH,
• (d) —C3-C7 cycloalkyl,
• (e) —(C1-C2 alkyl)-(C3-C7 cycloalkyl),
• (f) —(C1-C6 alkyl)-O—(C1-C3 alkyl),
• (g) —C2-C6 alkenyl
• (h) —C2-C6 alkynyl
• (i) —C1-C6 alkyl chain with one double bond and one triple bond,
• (j) —R1-aryl wherein R1-aryl at each occurrence is independently phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl, or tetralinyl each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently:
• (i) C1-C6 alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —NR1-aR1-b, —C≡N, —CF3, and C1-C3 alkoxy,
• (ii) C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of. —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (iii) C2-C6 alkynyl optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (iv) —F, Cl, —Br and —I,
• (v) —C1-C6 alkoxy optionally substituted with 1, 2, or 3 —F,
• (vi) —NRN-2RN-3,
• (vii) —OH,
• (viii) —C≡N,
• (ix) C3-C7 cycloalkyl, optionally substituted with 1, 2, or 3 groups that are selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (x) —CO—(C1-C4 alkyl),
• (xi) —SO2—NR1-aR1-b,
• (xii) —CO—NR1-aR1-b, or
• (xiii) —SO2—(C1-C4 alkyl),
• (k) —R1-heteroaryl wherein R1-heteroaryl at each occurrence is independently selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, pyridinyl-N-oxide, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, and benzothiopyranyl S,S-dioxide,
• where the R1-heteroaryl group is optionally substituted with 1, 2, 3, or 4 groups that are independently:
• (i) C1-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —NR1-aR1-b, —C≡N, —CF3, and C1-C3 alkoxy,
• (ii) C2-C6 alkenyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (iii) C2-C6 alkynyl optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (iv) —F, —Cl, —Br and —I,
• (v) —C1-C6 alkoxy optionally substituted with one, two, or three —F.
• (vi) —(CH2)0-4—NRN-2RN-3,
• (vii) —OH,
• (viii) —C≡N,
• (ix) (CH2)0-4—C3-C7 cycloalkyl, optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (x) (CH2)0-4—CO—(C1-C6 alkyl),
• (xi) (CH2)0-4—SO2—NRN-2RN-3,
• (xii) (CH2)0-4—CO—NRN-2RN-3,
• (xiii) (CH2)0-4—SO2—(C1-C6 alkyl),
• (xiv) (CH2)0-4—N(RN-2)—SO2—, and
• (xv) (CH2)0-4—N(RN-2)—C(O)—,
• (8) —(CH2)0-4—CO—(C1-C12 alkyl),
• (9) —(CH2)0-4—CO—(C2-C12 alkenyl),
• (10) —(CH2)0-4—CO—(C2-C12 alkynyl),
• (11) —(CH2)0-4—CO—(CH2)0-4(C3-C7 cycloalkyl),
• (12) —(CH2)0-4—CO—R1-aryl,
• (13) —(CH2)0-4—CO—R1-heteroaryl,
• (14) —(CH2)0-4—CO—R1-heterocycle wherein
• R1-heterocycle at each occurrence is independently selected from the group consisting of morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl S-oxide, tetrahydrothienyl S,S-dioxide, and homothiomorpholinyl S-oxide,
• where the R1-heterocycle group is bonded by any atom of the parent R1-heterocycle group substituted by hydrogen such that the new bond to the R1-heterocycle group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with 1, 2, 3, or 4 groups that are independently:
• (a) C1-C6 alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, halogen, —OH, —SH, —NR1-aR1-b—C≡N, —CF3, and C1-C3 alkoxy,
• (b) C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b
• (c) C2-C6 alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b
• (d) halogen,
• (e) C1-C6 alkoxy,
• (f) —C1-C6 alkoxy optionally substituted with one, two, or three —F,
• (g) —NRN-2RN-3,
• (h) —OH,
• (i) —C≡N,
• (j) (CH2)0-4—(C3-C7 cycloalkyl), optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (k) —(CH2)0-4—CO—(C1-C4 alkyl),
• (l) —(CH2)0-4—SO2—NR1-aR1-b,
• (m) —(CH2)0-4CO—NR1-aR1-b,
• (n) —(CH2)0-4—SO2—(C1-C6 alkyl), and
• (o) ═O,
• (p) —(CH2)0-4—N(RN-2)—SO2—
• (q) —(CH2)0-4—N(RN-2)—C(O)—
• (15) —(CH2)0-4—CO—RN-4 wherein
• RN-4 at each occurrence is independently selected from the group consisting of morpholinyl, thiomorpholinyl, pyrrolidinonyl, pyrrolyl, pyrazolyl, thienyl, pyridyl N-oxide, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl where each group is optionally substituted with 1, 2, 3, or 4 groups that are independently C1-C6 alkyl,
• (16) —(CH2)0-4—CO2—RN-5 where
• RN-5 at each occurrence is independently selected from the group consisting of:
• (a) C1-C6 alkyl,
• (b) —(CH2)0-2—(R1-aryl),
• (c) C2-C6 alkenyl,
• (d) C2-C6 alkynyl,
• (e) C3-C7 cycloalkyl, and
• (f) —(CH2)0-4—(R1-heteroaryl),
• (17) —(CH2)0-4—SO2—NRN-2RN-3
• (18) —(CH2)0-4—SO—(C1-C8 alkyl),
• (19) —(CH2)0-4—SO2—(C1-C12 alkyl),
• (20) —(CH2)0-4—SO2—(C3-C7 cycloalkyl),
• (21) —(CH2)0-4—N(H or RN-5)—CO2—RN-5,
• (22) —(CH2)0-4—N(H or RN-5)—CO—N(RN-5)2,
• (23) —(CH2)0-4—N—CS—N(RN-5)2,
• (24) —(CH2)0-4—N(—H or RN-5)—CO—RN-2,
• (25) —(CH2)0-4—NRN-2RN-3,
• (26) —(CH2)0-4—RN-4,
• (27) —(CH2)0-4—O—CO—(C1-C6 alkyl),
• (28) —(CH2)0-4—O—P(O)—(OR100)2 where R100 is independently H or C1-C4 alkyl,
• (29) —(CH2)0-4—O—CO—N(RN-5)2,
• (30) —(CH2)0-4—O—CS—N(RN-5)2,
• (31) —(CH2)0-4—O—(RN-5),
• (32) —(CH2)0-4—O—(RN-5)—COOH,
• (33) —(CH2)0-4—S—(RN-5),
• (34) —(CH2)0-4—O—(C1-C6 alkyl) wherein the alkyl group is optionally substituted with one, two, three, four, or five substituents independently selected from the group consisting of F, Cl, Br, and I,
• (35) —(CH2)0-4—(C3-C8 cycloalkyl),
• (36) C2-C6 alkenyl optionally substituted with C1-C3 alkyl, halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, or —NR1-aR1-b,
• (37) C2-C6 alkynyl optionally substituted with C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, or —NR1-aR1-b, and
• (38) —(CH2)0-4—N(—H or RN-5)—SO2—RN-2;
• (IV) —(CRC-xRC-y)0-4—RC-heteroaryl wherein RC-heteroaryl at each occurrence is independently selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzoisothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, henoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl,dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, imidazopyrazolyl, quinazolinonyl, pyrazopyridyl, benzooxadiazolyl, dihydropyrimidinonyl, dihydrobenzofuranonyl,
• where the RC-heteroaryl group is bonded by any atom of the parent RC-heteroaryl group substituted by hydrogen such that the new bond to the RC-heteroaryl group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted 1, 2, 3, or 4 groups that are independently:
• (1) C1-C6 alkyl, optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (2) —OH,
• (3) —NO2,
• (4) —F, —Cl, —Br, —I,
• (5) —CO—OH,
• (6) —C≡N,
• (V) C2-C10 alkenyl optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C6 alkoxy, —O-phenyl, and —NR1-aR1-b,
• (VI) C2-C10 alkynyl optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C6 alkoxy, —O-phenyl, and —NR1-aR1-b,
• (VII) —(C1-C6 alkyl)-O—(C1-C6 alkyl)-OH,
• (VIII) —CH2—NH—CH2—CH(—O—CH2—CH3)2,
• (IX) —(CH2)0-6—C(═NR1-a) (NR1-aR1-b);
• where RN is
• (I) RN-1—XN— where XN is —CO—, and where RN-1 is selected from the group consisting of:
• (A) phenyl, which is optionally substituted with one, two or three of the following substituents which can be the same or different and are:
• (1) C1-C6 alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• wherein R1-a and R1-b at each occurrence are independently H or C1-C6 alkyl,
• (2) —OH,
• (3) —NO2,
• (4) —F, —Cl, —Br, —I,
• (5) —CO2H,
• (6) —C≡N,
• (7) —(CH2)0-4—CO—NRN-2RN-3 where RN-2 and RN-3 are the same-or different and are selected from the group consisting of:
• (a) —H,
• (b) —C1-C8 alkyl optionally substituted with one substituent selected from the group consisting of:
• (i) —OH,
• (ii) —NH2,
• (iii) phenyl,
• (c) —C1-C8 alkyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —Br, or —I,
• (d) —C3-C8 cycloalkyl,
• (e) —(C1-C2 alkyl)-(C3-C8 cycloalkyl),
• (f) —(C1-C6 alkyl)-O—(C1-C3 alkyl),
• (g) —C2-C6 alkenyl,
• (h) —C2-C6 alkynyl,
• (i) —C1-C6 alkyl chain with one double bond and one triple bond,
• (j) —R1-aryl, wherein R1-aryl at each occurrence is independently phenyl, naphthyl, indanyl, indenyl, dihydronaphthyl, or tetralinyl each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently:
• (i) C1-C6 alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —NR1-aR1-b, —C≡N, —CF3, and C1-C3 alkoxy,
• (ii) C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (iii) C2-C6 alkynyl optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (iv) —F, Cl, —Br and —I,
• (v) —C1-C6 alkoxy optionally substituted with 1, 2, or 3 —F,
• (vi) —NRN-2RN-3,
• (vii) —OH,
• (viii) —C≡N,
• (ix) C3-C7 cycloalkyl, optionally substituted with 1, 2, or 3 groups that are selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (x) —CO—(C1-C4 alkyl),
• (xi) —SO2—NR1-aR1-b,
• (xii) —CO—NR1-aR1-b, or
• (xiii) —SO2—(C1-C4 alkyl),
• (k) —R1-heteroaryl, wherein R1-heteroaryl at each occurrence is independently selected from the group consisting of pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, pyridinyl-N-oxide, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, and benzothiopyranyl S,S-dioxide,
• where the R1-heteroaryl group is optionally substituted with 1, 2, 3, or 4 groups that are independently:
• (i) C1-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —NR1-aR1-b, —C≡N, —CF3, and C1-C3 alkoxy,
• (ii) C2-C6 alkenyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, or —NR1-aR1-b,
• (iii) C2-C6 alkynyl optionally substituted with 1, 2, or 3 groups that are independently —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, or —NR1-aR1-b,
• (iv) —F, —Cl, —Br and —I,
• (v) —C1-C6 alkoxy optionally substituted with one, two, or three —F,
• (vi) —(CH2)0-4—NRN-2RN-3,
• (vii) —OH,
• (viii) —C≡N,
• (ix) (CH2)0-4—C3-C7 cycloalkyl, optionally substituted with 1, 2, or 3 groups that are independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (x) (CH2)0-4—CO—(C1-C6 alkyl),
• (xi) (CH2)0-4—SO2—NRN-2RN-3,
• (xii) (CH2)0-4—CO—NRN-2RN-3,
• (xiii) (CH2)0-4—SO2—(C1-C6 alkyl),
• (xiv) (CH2)0-4—N(RN-2)—SO2—, and
• (xv) (CH2)0-4—N(RN-2)—C(O)—,
• (l) —R1-heterocyle, wherein
• R1-heterocycle at each occurrence is independently selected from the group consisting of morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl S-oxide, tetrahydrothienyl S,S-dioxide, and homothiomorpholinyl S-oxide,
• where the R1-heterocycle group is bonded by any atom of the parent R1-heterocycle group substituted by hydrogen such that the new bond to the R1-heterocycle group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with 1, 2, 3, or 4 groups that are independently:
• (a) C1-C6 alkyl optionally substituted with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, halogen, —OH, —SH, —NR1-aR1-b—C≡N, —CF3, and C1-C3 alkoxy,
• (b) C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b
• (c) C2-C6 alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b
• (d) halogen,
• (e) C1-C6 alkoxy,
• (f) —C1-C6 alkoxy optionally substituted with one, two, or three —F,
• (g) —NRN-2RN-3,
• (h) —OH,
• (i) —C≡N,
• (j) (CH2)0-4—(C3-C8 cycloalkyl), optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (k) —(CH2)0-4—CO—(C1-C4 alkyl),
• (l) —(CH2)0-4—SO2—NR1-aR1-b,
• (m) —(CH2)0-4—CO—NR1-aR1-b,
• (n) —(CH2)0-4—SO2—(C1-C6 alkyl), and
• (o) ═O,
• (p) —(CH2)0-4—N(RN-2)—SO2—
• (q) —(CH2)0-4—N(RN-2)—C(O)—
• (8) —(CH2)0-4—CO—(C1-C12 alkyl),
• (9) —(CH2)0-4—CO—(C2-C12 alkenyl),
• (10) —(CH2)0-4—CO—(C2-C12 alkynyl),
• (11) —(CH2)0-4—CO—(C3-C8 cycloalkyl),
• (12) —(CH2)0-4—CO—R1-aryl,
• (13) —(CH2)0-4—CO—R1-heteroaryl,
• (14) —(CH2)0-4—CO—R1-heterocycle,
• (15) —(CH2)0-4—CO—RN-4 wherein RN-4 is selected from the group consisting of phenyl, morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl, thienyl, pyrazolyl, pyridyl N-oxide, oxazolyl, thiazolyl, imidazolyl, and pyrrolidinyl where each group is optionally substituted with one, two, three, or four groups that are independently C1-C6 alkyl,
• (16) —(CH2)0-4—CO—O—RN-5 where RN-5 is selected from the group consisting of:
• (a) C1-C6 alkyl,
• (b) —(CH2)0-2—(R1-aryl).
• (c) C2-C6 alkenyl,
• (d) C2-C6 alkynyl,
• (e) —(CH2)0-2—C3-C8 cycloalkyl,
• (f) —(CH2)0-2—(R1-heteroaryl), and
• (g) —(CH2)0-2—(R1-heterocycle),
• (17) —(CH2)0-4—SO2—NRN-2RN-3,
• (18) —(CH2)0-4—SO—(C1-C8 alkyl),
• (19) —(CH2)0-4—SO2—(C1-C12 alkyl),
• (20) —(CH2)0-4—SO2—(C3-C8 cycloalkyl),
• (21) —(CH2)0-4—N(H or RN-5)—CO—O—RN-5,
• (22) —(CH2)0-4—N(H or RN-5)—CO—N(RN-5)2,
• (23) —(CH2)0-4—N—CS—N(RN-5)2,
• (24) —(CH2)0-4—N(H or RN-5)—CO—RN-2,
• (25) —(CH2)0-4—NRN-2RN-3,
• (26) —(CH2)0-4—RN-4,
• (27) —(CH2)0-4—O—CO—(C1-C6 alkyl),
• (28) —(CH2)0-4—O—P(O)—(OR100)2 wherein
• R100 at each occurrence is independently —H or C1-C4 alkyl,
• (29) —(CH2)0-4—O—CO—N(RN-5)2,
• (30) —(CH2)0-4—O—CS—N(RN-5)2,
• (31) —(CH2)0-4—O—(RN-5),
• (32) —(CH2)0-4—O—(RN-5)—COOH,
• (33) —(CH2)0-4—S—(RN-5),
• (34) —(CH2)0-4—O—(C1-C6 alkyl optionally substituted with one, two, three, four, or five of —F),
• (35) C3-C8 cycloalkyl,
• (36) C2-C6 alkenyl optionally substituted with C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, or —NR1-aR1-b,
• (37) C2-C6 alkynyl optionally substituted with C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, or —NR1-aR1-b,
• (38) —(CH2)0-4—N(H or RN-5)—SO2—RN-2,
• (39) —(CH2)1-4—(C3-C8 cycloalkyl),
• (B) —RN-heteroaryl where RN-heteroaryl is selected from the group consisting of pyridinyl, indolyl, indolinyl, isoindolyl, imidazolyl, isoxazolyl, oxazolyl, thiazolyl, indolizinyl and isochromanyl,
• where the RN-heteroaryl group is bonded by any atom of the parent RN-heteroaryl group substituted by hydrogen such that the new bond to the RN-heteroaryl group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three, or four of:
• (1) C1-C6 alkyl, optionally substituted with one, two or three substituents selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (2) —OH,
• (3) —NO2,
• (4) —F, —Cl, —Br, —I,
• (5) —CO2H,
• (6) —C≡N,
• (7) —(CH2)0-4—CO—NRN-2RN-3,
• (8) —(CH2)0-4—CO—(C1-C12 alkyl),
• (9) —(CH2)0-4—CO—(C2-C12 alkenyl),
• (10) —(CH2)0-4—CO—(C2-C12 alkynyl),
• (11) —(CH2)0-4—CO—(C3-C8 cycloalkyl),
• (12) —(CH2)0-4—CO—NR1-aryl,
• (13) —(CH2)0-4—CO—R1-heteroaryl,
• (14) —(CH2)0-4—CO—R1-heterocycle,
• (15) —(CH2)0-4—CO—RN-4
• (16) —(CH2)0-4—CO—O—RN-5
• (17) —(CH2)0-4—SO2—NRN-2RN-3,
• (18) —(CH2)0-4—SO—(C1-C8 alkyl),
• (19) —(CH2)0-4—SO2-(C1-C12 alkyl),
• (20) —(CH2)0-4—SO2—(C3-C8 cycloalkyl),
• (21) —(CH2)0-4—N(H or RN-5)—CO—O—RN-5,
• (22) —(CH2)0-4—N(H or RN-5 )—CO—N(RN-5)2,
• (23) —(CH2)0-4—N—CS—N(RN-5)2,
• (24) —(CH2)0-4—N(—H or RN-5)—CO—RN-2,
• (25) —(CH2)0-4—NRN-2RN-3,
• (26) —(CH2)0-4—RN-4,
• (27) —(CH2)0-4—O—CO—(C1-C6 alkyl),
• (28) —(CH2)0-4—O—P(O)—(OR100)2,
• (29) —(CH2)0-4—O—CO—N(RN-5)2,
• (30) —(CH2)0-4—O—CS—N(RN-5)2,
• (31) —(CH2)0-4—O—(RN-5),
• (32) —(CH2)0-4—O—(RN-5)—COOH,
• (33) —(CH2)0-4—S—(RN-5),
• (34) —(CH2)0-4—O—(C1-C6 alkyl optionally substituted with one, two, three, four, or five of —F),
• (35) C3-C8 cycloalkyl,
• (36) C2-C6 alkenyl optionally substituted with C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, or —NR1-aR1-b,
• (37) C2-C6 alkynyl optionally substituted with C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, or —NR1-aR1-b,
• (38) —(CH2)0-4—N(—H or RN-5)—SO2—RN-2,
• (39) —(CH2)1-4—C3-C8 cycloalkyl,
• (C) RN-aryl—W—RN-aryl,
• (D) RN-aryl—W—RN-heteroaryl,
• (E) RN-aryl—W—R1-heterocycle,
• (F) RN-heteroaryl—W—RN-aryl,
• (G) RN-heteroaryl—W—RN-heteroaryl,
• (H) RN-heteroaryl—W—RN-1-heterocycle,
• (I) RN-heterocycle—W—RN-aryl,
• (J) RN-heterocycle—W—RN-heteroaryl,
• (K) RN-heterocycle—W—RN-1-heterocycle,
• where W is
• (25) —(CH2)1-4—,
• (26) —O—,
• (27) —S(O)0-2—,
• (28) —N(RN-5)—,
• (29) —CO—;
• or
• (30) a bond;
• (II) —CO—(C1-C6 alkyl)-M-(C1-C6 alkyl), where M is S, SO or SO2, and wherein each alkyl is unsubstituted or substituted with one, two, or three of substituents independently selected from the group consisting of:
• (A) —NH—CO—(C1-C6 alkyl),
• (B) —NH—CO—O—RN-8,
• (C) —NRN-2RN-3;
• where R1 is
• (CH2)n1-phenyl, where n1 is zero or one, and which is optionally substituted with one, two, three or four of the following substituents on the phenyl ring:
• (A) C1-C6 alkyl optionally substituted with one, two or three substituents selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (B) C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (C) C2-C6 alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (D) —F, Cl, —Br or —I,
• (F) —C1-C6 alkoxy optionally substituted with one, two or three of —F,
• (G) —NRN-2RN-3 where RN-2 and RN-3 are as defined below,
• (H) —OH,
• (I) —C≡N,
• (J) C3-C7 cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (K) —CO—(C1-C4 alkyl),
• (L) —SO2—NR1-aR1-b,
• (M) —CO—NR1-aR1-b,
• (N) —SO2—(C1-C4 alkyl);
• and
• where R2 is
• (I) -(Z)-C1-C6 alkyl, where Z is a bond, —C(O)—, —CO2— or —SO2—, wherein the alkyl group is optionally substituted with one, two or three substituents selected from the group consisting of C1-C3 alkyl, C1-C7 alkyl (optionally substituted with C1-C3 alkyl and C1-C3 alkoxy), —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, —NR1-aR1-b where R1-a and R1-b are independently —H or C1-C6 alkyl, and —OC═O NR1-aR1-b,
• (II) -(Z)-CH2—S(O)0-2—(C1-C6 alkyl),
• (III) -(Z)-CH2—CH2—S(O)0-2—(C1-C6 alkyl),
• (IV) -(Z)-C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (V) -(Z)-C2-C6 alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (VI) -(Z)-(CH2)n1—(R1-aryl), where Z is a bond, CO, CO2 or SO2, where n, is zero or one and where R1-aryl is phenyl, 1-naphthyl, 2-naphthyl and indanyl, indenyl, dihydronaphthalyl, or tetralinyl optionally substituted with one, two, three or four of the following substituents on the aryl ring:
• (A) C1-C6 alkyl optionally substituted with one, two or three substituents selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (B) C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (C) C2-C6 alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (D) —F, Cl, —Br or —I,
• (F) —C1-C6 alkoxy optionally substituted with one, two or three of —F,
• (G) —NRN-2RN-3 where RN-2 and RN-3 are as defined below,
• (H) —OH,
• (I) —C≡N,
• (J) C3-C7 cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (K) —CO—(C1-C4 alkyl),
• (L) —SO2—NR1-aR1-b,
• (M) —CO—NR1-aR1-b,
• (N) —SO2—(C1-C4 alkyl),
• (VII) -(Z)-(CH2)n1—(R1-heteroaryl) where n1 is as defined above and where R1-heteroaryl is selected from the group consisting of:
• pyridinyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, pyridinyl-N-oxide, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S-dioxide,
• where the R1-heteroaryl group is bonded to —(CH2)n1— by any ring atom of the parent RN-heteroaryl group substituted by hydrogen such that the new bond to the R1-heteroaryl group replaces the hydrogen atom and its bond, where heteroaryl is optionally substituted with one, two, three or four of:
• (1) C1-C6 alkyl optionally substituted with one, two or three substituents selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (2) C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (3) C2-C6 alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (4) —F, Cl, —Br or —I,
• (6) —C1-C6 alkoxy optionally substituted with one, two, or three of —F,
• (7) —NRN-2RN-3 where RN-2 and RN-3 are as defined below,
• (8) —OH,
• (9) —C≡N,
• (10) C3-C7 cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (11) —CO—(C1-C4 alkyl),
• (12) —SO2—NR1-aR1-b,
• (13) —CO—NR1-aR1-b, or
• (14) —SO2—(C1-C4 alkyl), with the proviso that when n1 is zero R-heteroaryl is not bonded to the carbon chain by nitrogen, or
• (VIII) -(Z)-(CH2)n1—(R1-heterocycle) where n1 is as defined above and R1-heterocycle is selected from the group consisting of:
• morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl dihydropyrazinyl dihydropyridinyl dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl S-oxide, tetrahydrothienyl S,S-dioxide, homothiomorpholinyl S-oxide,
• where the R1-heterocycle group is bonded by any atom of the parent R1-heterocycle group substituted by hydrogen such that the new bond to the R1-heterocycle group replaces the hydrogen atom and its bond, where heterocycle is optionally substituted with one, two, three or four:
• (1) C1-C6 alkyl optionally substituted with one, two or three substituents selected from the group consisting of C1-C3 alkyl, —F, —Cl, —Br, —I, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (2) C2-C6 alkenyl with one or two double bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (3) C2-C6 alkynyl with one or two triple bonds, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (4) —F, Cl, —Br, or —I,
• (5) C1-C6 alkoxy,
• (6) —C1-C6 alkoxy optionally substituted with one, two, or three —F,
• (7) —NRN-2RN-3 where RN-2 and RN-3 are as defined below,
• (8) —OH,
• (9) —C≡N,
• (10) C3-C7 cycloalkyl, optionally substituted with one, two or three substituents selected from the group consisting of —F, —Cl, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, and —NR1-aR1-b,
• (11) —CO—(C1-C4 alkyl),
• (12) —SO2—NR1-aR1-b,
• (13) —CO—NR1-aR1-b,
• (14) —SO2—(C1-C4 alkyl),
• (15) ═O, with the proviso that when n1 is zero R1-heterocycle is not bonded to the carbon chain by nitrogen;
• and
• where R20 is H or C1-6 alkyl or alkenyl.