US 2013/0210704 A1Published application

Novel cyclosporin derivatives and uses thereof

AssigneeS&T Global Inc.

InventorsZhuang SU, Zhengyu LONG, Zhennian HUANG, Suizhou YANG

Life of this patent

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Abstract

The present invention relates to a compound of the Formula (I)): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.

Claims54

Dependent claims

A compound of Formula (I):

or pharmaceutically acceptable salt thereof, wherein:
R8 is n-butyl, (E)-but-2-enyl, or
—(CH2)4—SR9, —(CH2)4—(C═O)OR9, or —(CH2)3—(C═O)OR9;
each occurrence of R9 is independently hydrogen or (C1-C6)alkyl;
R2 is ethyl, 1-hydroxyethyl, isopropyl or n-propyl;
W is O, S, CH2, or NR1;
R1 is hydrogen;
(C1-C6)alkyl, optionally substituted by one or more groups RD which may be the same or different;
(C2-C6)alkenyl or (C2-C6)alkynyl;
(C3-C7)cycloalkyl optionally substituted with (C1-C6)alkyl;
phenyl optionally substituted with from one to five groups which may be the same or different selected from halogen, —O(C1-C6)alkyl, —C(═O)O(C1-C6)alkyl, amino, alkylamino and dialkylamino;
or a heterocyclic ring which may be saturated or unsaturated containing five or six ring atoms and from one to three heteroatoms which may be the same or different selected from nitrogen, sulfur and oxygen;
or R1 and R3 together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to four groups which may be the same or different selected from the group consisting of (C1-C6)alkyl, phenyl and benzyl;
R3 is:
H;
(C1-C6)alkyl, optionally substituted by one or more groups R4 which may be the same or different;
(C2-C6)alkenyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
(C2-C6)alkynyl, optionally substituted by one or one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
(C3-C7)cycloalkyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
phenyl or CH2-phenyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, (C1-C6)alkyl;
R7 is
R5 is:
H;
(C1-C6)alkyl, optionally substituted by one or more groups R6 which may be the same or different;
(C2-C6)alkenyl, optionally substituted by one or more groups which may be the same or different selected from hydroxy, (C1-C6)alkyl, aryl (e.g., phenyl), (CH2)pORA, O(CH2)mOH, O(CH2)mO(CH2)mOH, O(CH2)mNRARB, O(CH2)mO(CH2)mNRARB, (CH2)pNRARB, (CH2)pNRC(CH2)mNRARB, (CH2)pNRC(CH2)mNRC(CH2)mNRARB, (CH2)pC(═O)NRARB, (CH2)pC(═O)ORA;
(C2-C6)alkynyl, optionally substituted by one or one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
(C3-C7)cycloalkyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
phenyl or CH2-phenyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, (C1-C6)alkyl, (CH2)pORA, (CH2)pNRARB, (CH2)pC(═O)NRARB, (CH2)pC(═O)ORA;
each occurrence of R4 is independently halogen, hydroxy, aryl (e.g., phenyl), O(CH2)mORA, O(CH2)mO(CH2)mORA, C(═O)(C1-C6)alkyl, C(═O)ORA, C(═O)NRARB, —NRARB, —NRCCH2(CH2)pNRARB, NRC[CH2(CH2)pNRA]mCH2(CH2)nNRARB, O[CH2(CH2)pO]mCH2(CH2)nORA, OCH2(CH2)pNRARB, or O[CH2(CH2)pO]mCH2(CH2)nNRARB;
each occurrence of R6 is independently halogen, hydroxy, aryl (e.g., phenyl), S(C1-C6)alkyl, SRA, ORA, O(CH2)mORA, O(CH2)mO(CH2)mORA, C(═O)ORA, C(═O)NRARB, NRARB, O(CH2)mNRARB, O(CH2)mO(CH2)mNRARB, NRC(CH2)mNRARB, or NRC(CH2)mNRC(CH2)mNRARB, wherein said aryl or phenyl is optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, (C1-C6)alkyl, (CH2)pORA, (CH2)pNRARB, (CH2)pC(═O)NRARB and (CH2)pC(═O)ORA;
each occurrence of RA and RB is independently:
hydrogen;
(C1-C6)alkyl, optionally substituted by one or more groups RD which may be the same or different;
(C2-C6)alkenyl or (C2-C6)alkynyl;
(C3-C7)cycloalkyl optionally substituted with (C1-C6)alkyl;
phenyl optionally substituted with from one to five groups which may be the same or different selected from halogen, —O(C1-C6)alkyl, —C(═O)O(C1-C6)alkyl, amino, alkylamino and dialkylamino;
or a heterocyclic ring which may be saturated or unsaturated containing five or six ring atoms and from one to three heteroatoms which may be the same or different selected from nitrogen, sulfur and oxygen;
or RA and RB, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to four groups which may be the same or different selected from the group consisting of alkyl, phenyl and benzyl;
each occurrence of RC is independently hydrogen or (C1-C6)alkyl;
p is an integer of 0, 1, 2, 3, 4, or 5;
and
m is an integer of 1, 2, 3, 4 or 5.

39 more elements

A compound of Formula (I):

or pharmaceutically acceptable salt thereof, wherein:
R8 is n-butyl, (E)-but-2-enyl, or
—(CH2)4—SR9, —(CH2)4—(C═O)OR9, or —(CH2)3—(C═O)OR9;
each occurrence of R9 is independently hydrogen or (C1-C6)alkyl;
R2 is ethyl, 1-hydroxyethyl, isopropyl or n-propyl;
W is O, S, CH2, or NR1;
R1 is hydrogen;
(C1-C6)alkyl, optionally substituted by one or more groups RD which may be the same or different;
(C2-C6)alkenyl or (C2-C6)alkynyl;
(C3-C7)cycloalkyl optionally substituted with (C1-C6)alkyl;
phenyl optionally substituted with from one to five groups which may be the same or different selected from halogen, —O(C1-C6)alkyl, —C(═O)O(C1-C6)alkyl, amino, alkylamino and dialkylamino;
or a heterocyclic ring which may be saturated or unsaturated containing five or six ring atoms and from one to three heteroatoms which may be the same or different selected from nitrogen, sulfur and oxygen;
or R1 and R3 together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to four groups which may be the same or different selected from the group consisting of (C1-C6)alkyl, phenyl and benzyl;
R3 is:
H;
(C7-C12)alkyl, optionally substituted by one or more groups R4 which may be the same or different;
(C7-C12)alkenyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
or
(C7-C12)alkynyl, optionally substituted by one or one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
R7 is
R5 is:
H;
(C1-C6)alkyl, optionally substituted by one or more groups R6 which may be the same or different;
(C2-C6)alkenyl, optionally substituted by one or more groups which may be the same or different selected from hydroxy, (C1-C6)alkyl, aryl (e.g., phenyl), (CH2)pORA, O(CH2)mOH, O(CH2)mO(CH2)mOH, O(CH2)mNRARB, O(CH2)mO(CH2)mNRARB, (CH2)pNRARB, (CH2)pNRC(CH2)mNRARB, (CH2)pNRC(CH2)mNRC(CH2)mNRARB, (CH2)pC(═O)NRARB, (CH2)pC(═O)ORA;
(C2-C6)alkynyl, optionally substituted by one or one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
(C3-C7)cycloalkyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
phenyl or CH2-phenyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, (C1-C6)alkyl, (CH2)pORA, (CH2)pNRARB, (CH2)pC(═O)NRARB, (CH2)pC(═O)ORA;
each occurrence of R4 is independently halogen, hydroxy, (C3-C7)cycloalkyl, aryl (e.g., phenyl), O(CH2)mORA, O(CH2)mO(CH2)mORA, C(═O)(C1-C6)alkyl, C(═O)ORA, C(═O)NRARB, —NRARB, —NRCCH2(CH2)pNRARB, NRC[CH2(CH2)pNRA]mCH2(CH2)nNRARB, O[CH2(CH2)pO]mCH2(CH2)nORA, OCH2(CH2)pNRARB, or O[CH2(CH2)pO]mCH2(CH2)nNRARB;
each occurrence of R6 is independently halogen, hydroxy, aryl (e.g., phenyl), S(C1-C6)alkyl, SRA, ORA, O(CH2)mORA, O(CH2)mO(CH2)mORA, C(═O)ORA, C(═O)NRARB, NRARB, O(CH2)mNRARB, O(CH2)mO(CH2)mNRARB, NRC(CH2)mNRARB, or NRC(CH2)mNRC(CH2)mNRARB, wherein said aryl or phenyl is optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, (C1-C6)alkyl, (CH2)pORA, (CH2)pNRARB, (CH2)pC(═O)NRARB and (CH2)pC(═O)ORA;
each occurrence of RA and RB is independently:
hydrogen;
(C1-C6)alkyl, optionally substituted by one or more groups RD which may be the same or different;
(C2-C6)alkenyl or (C2-C6)alkynyl;
(C3-C7)cycloalkyl optionally substituted with (C1-C6)alkyl;
phenyl optionally substituted with from one to five groups which may be the same or different selected from halogen, —O(C1-C6)alkyl, —C(═O)O(C1-C6)alkyl, amino, alkylamino and dialkylamino;
or a heterocyclic ring which may be saturated or unsaturated containing five or six ring atoms and from one to three heteroatoms which may be the same or different selected from nitrogen, sulfur and oxygen;
or RA and RB, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to four groups which may be the same or different selected from the group consisting of alkyl, phenyl and benzyl;
each occurrence of RR is independently hydrogen or (C1-C6)alkyl;
p is an integer of 0, 1, 2, 3, 4, or 5;
and
m is an integer of 1, 2, 3, 4 or 5.

38 more elements

A compound selected from:

[(R)-(2-(N,N-Dimethylamino)ethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(2-(N,N-Diethylamino)ethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(2-(N-Morpholino)ethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(2-(N-Pyrrolidinyl)ethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(2-(N-Piperidinyl)ethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(3-(N,N-Dimethylamino)propoxy)methyl-Sar]-3-cyclosporin,
[(R)-(3-(N,N-Diethylamino)propoxy)methyl-Sar]-3-cyclosporin,
[(R)-(3-(N-Morphlino)propoxy)methyl-Sar]-3-cyclosporin,
[(R)-(3-(N-Pyrrolidinyl)propoxy)methyl-Sar]-3-cyclosporin,
[(R)-(3-(N-Piperidinyl)propoxy)methyl-Sar]-3-cyclosporin,
[(R)-(Carboxymethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(Carboxymethoxy)methyl-Sar]-3-cyclosporin sodium salt,
[(R)-(Carboxymethoxy)methyl-Sar]-3-cyclosporin potassium salt,
[(R)-(Methoxycarboxymethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(Carboxyethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(Carboxyethoxy)methyl-Sar]-3-cyclosporin sodium salt,
[(R)-(Carboxyethoxy)methyl-Sar]-3-cyclosporin potassium salt,
[(R)-(Methoxycarboxyethoxy)methyl-Sar]-3-cyclosporin,
[(R)-(Carboxypropoxy)methyl-Sar]-3-cyclosporin,
[(R)-(Carboxypropoxy)methyl-Sar]-3-cyclosporin sodium salt,
[(R)-(Carboxypropoxy)methyl-Sar]-3-cyclosporin potassium salt,
[(R)-(Methoxycarboxypropoxy)methyl-Sar]-3-cyclosporin,
[(R)-(Carboxypentyloxy)methyl-Sar]-3-cyclosporin,
[(R)-(Carboxypentyloxy)methyl-Sar]-3-cyclosporin sodium salt,
[(R)-(Carboxypentyloxy)methyl-Sar]-3-cyclosporin potassium salt,
[(R)-(Methoxycarboxypentyloxy)methyl-Sar]-3-cyclosporin,
[(R)-[([HO-Gly-(D-Glu)6]carbamoyl)methoxy]methyl-Sar]-3-cyclosporin,
[(R)-[([HO-Gly-(D-Glu)6]carbamoyl)ethoxy]methyl-Sar]-3-cyclosporin,
[(R)-[([HO-Gly-(D-Glu)6]carbamoyl)propoxy]methyl-Sar]-3-cyclosporin,
[(R)-((2-[([HO-Gly-(D-Glu)6]carbamoyl)methoxy]ethoxy)methyl-Sar]-3-cyclosporin,
[(R)-((3-[([HO-Gly-(D-Glu)6]carbamoyl)methoxy]propoxy)methyl-Sar]-3-cyclosporin,
[(R)-((4-[([HO-Gly-(D-Glu)6]carbamoyl)methoxy]butoxy)methyl-Sar]-3-cyclosporin,
[(R)-((5-[([HO-Gly-(D-Glu)6]carbamoyl)methoxy]pentyloxy)methyl-Sar]-3-cyclosporin,
[(R)-((6-[([HO-Gly-(D-Glu)6]carbamoyl)methoxy]hexyloxy)methyl-Sar]-3-cyclosporin,
[(R)-(2-(N-Neopentylamino)ethylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Neopentylamino)ethylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Methyl-N-Neopentylamino)ethylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Methyl-N-Neopentylamino)ethylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Ethyl-N-Neopentylamino)ethylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Ethyl-N-Neopentylamino)ethylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Neopentylamino)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Neopentylamino)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Methyl-N-Neopentylamino)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Methyl-N-Neopentylamino)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Ethyl-N-Neopentylamino)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Ethyl-N-Neopentylamino)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Neopentylamino)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Neopentylamino)butylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Methyl-N-Neopentylamino)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Methyl-N-Neopentylamino)butylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Ethyl-N-Neopentylamino)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Ethyl-N-Neopentylamino)butylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Neopentylamino)ethoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Neopentylamino)ethoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Methyl-N-Neopentylamino)ethoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Methyl-N-Neopentylamino)ethoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Ethyl-N-Neopentylamino)ethoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Ethyl-N-Neopentylamino)ethoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Neopentylamino)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Neopentylamino)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Methyl-N-Neopentylamino)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Methyl-N-Neopentylamino)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Ethyl-N-Neopentylamino)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Ethyl-N-Neopentylamino)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Neopentylamino)butoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Neopentylamino)butoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Methyl-N-Neopentylamino)butoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Methyl-N-Neopentylamino)butoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Ethyl-N-Neopentylamino)butoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Ethyl-N-Neopentylamino)butoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Morpholino)ethylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Morpholino)ethylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Thiomorpholino)ethylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Thiomorpholino)ethylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Morpholino)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Morpholino)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Thiomorpholino)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Thiomorpholino)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Morpholino)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Morpholino)butylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Thiomorpholino)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Thiomorpholino)butylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Morpholino)ethoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Morpholino)ethoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Thiomorpholino)ethoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N-Thiomorpholino)ethoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Morpholino)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Morpholino)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Morpholino)propoxy)methyl-Sar]-3-[(γ-allyloxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Thiomorpholino)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Thiomorpholino)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Thiomorpholino)propoxy)methyl-Sar]-3-[(γ-allyloxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Morpholino)butoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Morpholino)butoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Morpholino)butoxy)methyl-Sar]-3-[(γ-allyloxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Thiomorpholino)butoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Thiomorpholino)butoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Thiomorpholino)butoxy)methyl-Sar]-3-[(γ-allyloxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(4-Ethyl-N-piperazinyl)ethylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(4-Ethyl-N-piperazinyl)ethylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Methyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Methyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Ethyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Ethyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Propyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Propyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Propyl-N-piperazinyl)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Propyl-N-piperazinyl)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Isopropyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Isopropyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Isopropyl-N-piperazinyl)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Isopropyl-N-piperazinyl)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Isobutyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Isobutyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Isobutyl-N-piperazinyl)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin
[(R)-(3-(4-Isobutyl-N-piperazinyl)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Neopentyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin
[(R)-(3-(4-Neopentyl-N-piperazinyl)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Neopentyl-N-piperazinyl)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(4-Neopentyl-N-piperazinyl)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N,N-Diethylamino)ethylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N,N-Diethylamino)ethylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N,N-Diethylamino)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N,N-Diethylamino)propylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N,N-Diethylamino)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N,N-Diethylamino)butylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N,N-Diethylamino)ethoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(2-(N,N-Diethylamino)ethoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N,N-Diethylamino)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N,N-Diethylamino)propoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N,N-Diethylamino)butoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N,N-Diethylamino)butoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N,N-Diisobutylamino)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N,N-Diisobutylamino)propylthio)methyl-Sar]-3-[(γ-Methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N,N-Diisobutylamino)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N,N-Diisobutylamino)butylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N,N-Diisobutylamino)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N,N-Diisobutylamino)propoxy)methyl-Sar]-3-[(γ-Methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N,N-Diisobutylamino)butoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N,N-Diisobutylamino)butoxy)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(2-(N,N-Diethylamino)ethoxy)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(2-(N,N-Diethylamino)ethoxy)butylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-Hydroxylpropylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-Methoxypropylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-Hydroxyl-3,3-dimethylpropylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-Hydroxylpropylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-Methoxypropylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-Hydroxyl-3,3-dimethylpropylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-Hydroxylbutylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-Methoxybutylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-Hydroxyl-4,4-dimethylbutylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-Hydroxylbutylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-Methoxybutylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-Hydroxyl-4,4-dimethylbutylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(5-Hydroxylpentylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(5-Methoxypentylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(5-Hydroxyl-5,5-dimethylpentylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(5-Hydroxylpentylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(5-Methoxypentylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(5-Hydroxyl-5,5-dimethylpentylthio)methyl-Sar]-3-[(γ-methoxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Piperidinyl)propylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Piperidinyl)propylthio)methyl-Sar]-3-[(γ-methox)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Piperidinyl)propoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(3-(N-Piperidinyl)propoxy)methyl-Sar]-3-[(γ-methox)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Piperidinyl)butylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Piperidinyl)butylthio)methyl-Sar]-3-[(γ-methox)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Piperidinyl)butoxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(4-(N-Piperidinyl)butoxy)methyl-Sar]-3-[(γ-methox)-N-MeLeu]-4-cyclosporin,
[(S)-(5-Carboxyheptylthio)methyl-Sar]-3-cyclosporin,
[(S)-(5-Carboxyheptylthio)methyl-Sar]-3-cyclosporin-potassium salt,
[(S)-(5-(Ethoxycarbonyl)heptylthio)methyl-Sar]-3-cyclosporin,
[(S)-((7,7′-Dicarboxy)heptylthio)methyl-Sar]-3-cyclosporin,
[(S)-((7,7′-Dicarboxy)heptylthio)methyl-Sar]-3-cyclosporin-dipotassium salt,
[(S)-((7,7′-Dicarboxy)heptylthio)methyl-Sar]-3-cyclosporin-disodium salt,
[(S)-(7,7′-Diethoxycarbonyl)heptylthio)methyl-Sar]-3-cyclosporin,
[(S)-(((R)-3-Hydroxymethyl-6-(imidazol-1-yl)hexyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((S)-3-Hydroxymethyl-6-(imidazo-1-yl)hexyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-((((R)-3-Hydroxymethyl-6-morpholinohexyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-((((S)-3-Hydroxymethyl-6-morpholinohexyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((R)-3-Hydroxymethyl-6-(4-ethylpiperazin-1-yl)hexyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((S)-3-Hydroxymethyl-6-(4-isopropylpiperazin-1-yl)hexyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((S)-4-Hydroxy-7-(imidazol-1-yl)heptyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((R)-4-Hydroxy-7-(imidazo-1-yl)heptyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((S)-4-Hydroxy-7-morpholinoheptyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((R)-4-Hydroxy-7-morpholinoheptyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((S)-4-Hydroxy-7-(4-ethylpiperazin-1-yl)heptyl)thio)methyl-Sar]-3-cyclosporin,
[(S)-(((R)-4-Hydroxy-7-(4-ethylpiperazin-1-yl)heptyl)thio)methyl-Sar]-3-cyclosporin,
[(R)-(5-Carboxyheptyloxy)methyl-Sar]-3-cyclosporin,
[(R)-(5-Carboxyheptyloxy)methyl-Sar]-3-cyclosporin-potassium salt,
[(R)-((7,7′-Dicarboxy)heptyloxy)methyl-Sar]-3-cyclosporin,
[(R)-((7,7′-Dicarboxy)heptyloxy)methyl-Sar]-3-cyclosporin-dipotassium salt,
[(R)-(7,7′-Diethoxycarbonyl)heptyloxy)methyl-Sar]-3-cyclosporin,
[(R)-(((S)-4-Hydroxy-7-(imidazol-1-yl)heptyl)oxy)methyl-Sar]-3-cyclosporin,
[(R)-(((R)-4-Hydroxy-7-(imidazo-1-yl)heptyl)oxy)methyl-Sar]-3-cyclosporin,
[(R)-(((S)-4-Hydroxy-7-morpholinoheptyl)oxy)methyl-Sar]-3-cyclosporin,
[(R)-(((R)-4-Hydroxy-7-morpholinoheptyl)oxy)methyl-Sar]-3-cyclosporin,
[(R)-(((S)-4-Hydroxy-7-(4-ethylpiperazin-1-yl)heptylcyclos)oxy)methyl-Sar]-3-cyclosporin,
[(R)-(((R)-4-Hydroxy-7-(4-ethylpiperazin-1-yl)heptyl)oxy)methyl-Sar]-3-cyclosporin,
[(S)-(7,7′-Di(carboxy)heptylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(7,7′-Di(carboxy)heptylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin-dipotassium salt,
[(S)-(7,7′-Di(ethoxycarbonyl)heptylthio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((S)-4-Hydroxy-7-(imidazol-1-yl)heptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((R)-4-Hydroxy-7-(imidazo-1-yl)heptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((S)-4-Hydroxy-7-morpholinoheptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((R)-4-Hydroxy-7-morpholinoheptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((S)-4-Hydroxy-7-(4-ethylpiperazin-1-yl)heptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((R)-4-Hydroxy-7-(4-ethylpiperazin-1-yl)heptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((R)-3-Hydroxymethyl-6-(imidazol-1-yl)hexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((S)-3-Hydroxymethyl-6-(imidazo-1-yl)hexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((R)-3-Hydroxymethyl-6-morpholinohexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((S)-3-Hydroxymethyl-6-morpholinohexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((R)-3-Hydroxymethyl-6-(4-ethylpiperazin-1-yl)hexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(S)-(((S)-3-Hydroxymethyl-6-(4-isopropylpiperazin-1-yl)hexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(7,7′-Di(carboxy)heptyloxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin
[(R)-(7,7′-Di(carboxy)heptyloxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin-dipotassium salt,
[(R)-(7,7′-Di(ethoxycarbonyl)heptyloxy)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((S)-4-Hydroxy-7-(imidazol-1-yl)heptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((R)-4-Hydroxy-7-(imidazo-1-yl)heptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((S)-4-Hydroxy-7-morpholinoheptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((R)-4-Hydroxy-7-morpholinoheptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((S)-4-Hydroxy-7-(4-ethylpiperazin-1-yl)heptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((R)-4-Hydroxy-7-(4-ethylpiperazin-1-yl)heptyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((R)-3-Hydroxymethyl-6-(imidazol-1-yl)hexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((S)-3-Hydroxymethyl-6-(imidazo-1-yl)hexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((R)-3-Hydroxymethyl-6-morpholinohexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((S)-3-Hydroxymethyl-6-morpholinohexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin,
[(R)-(((R)-3-Hydroxymethyl-6-(4-ethylpiperazin-1-yl)hexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin, and
[(R)-(((S)-3-Hydroxymethyl-6-(4-isopropylpiperazin-1-yl)hexyl)thio)methyl-Sar]-3-[(γ-hydroxy)-N-MeLeu]-4-cyclosporin, or a pharmaceutically acceptable salt thereof.

225 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of Formula (I):

or pharmaceutically acceptable salt thereof, wherein:
R8 is n-butyl, (E)-but-2-enyl, or
—(CH2)4—SR9, —(CH2)4—(C═O)OR9, or —(CH2)3—(C═O)OR9;
each occurrence of R9 is independently hydrogen or (C1-C6)alkyl;
R2 is ethyl, 1-hydroxyethyl, isopropyl or n-propyl;
W is O, S, CH2, or NR1;
R1 is hydrogen;
(C1-C6)alkyl, optionally substituted by one or more groups RD which may be the same or different;
(C2-C6)alkenyl or (C2-C6)alkynyl;
(C3-C7)cycloalkyl optionally substituted with (C1-C6)alkyl;
phenyl optionally substituted with from one to five groups which may be the same or different selected from halogen, —O(C1-C6)alkyl, —C(═O)O(C1-C6)alkyl, amino, alkylamino and dialkylamino;
or a heterocyclic ring which may be saturated or unsaturated containing five or six ring atoms and from one to three heteroatoms which may be the same or different selected from nitrogen, sulfur and oxygen;
or R1 and R3 together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to four groups which may be the same or different selected from the group consisting of (C1-C6)alkyl, phenyl and benzyl;
R3 is:
H;
(C1-C6)alkyl, optionally substituted by one or more groups R4 which may be the same or different;
(C2-C6)alkenyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
(C2-C6)alkynyl, optionally substituted by one or one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
(C3-C7)cycloalkyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
phenyl or CH2-phenyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, (C1-C6)alkyl;
R7 is
R5 is:
H;
(C1-C6)alkyl, optionally substituted by one or more groups R6 which may be the same or different;
(C2-C6)alkenyl, optionally substituted by one or more groups which may be the same or different selected from hydroxy, (C1-C6)alkyl, aryl (e.g., phenyl), (CH2)pORA, O(CH2)mOH, O(CH2)mO(CH2)mOH, O(CH2)mNRARB, O(CH2)mO(CH2)mNRARB, (CH2)pNRARB, (CH2)pNRC(CH2)mNRARB, (CH2)pNRC(CH2)mNRC(CH2)mNRARB, (CH2)pC(═O)NRARB, (CH2)pC(═O)ORA;
(C2-C6)alkynyl, optionally substituted by one or one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
(C3-C7)cycloalkyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, amino, monoalkylamino and dialkylamino;
phenyl or CH2-phenyl, optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, (C1-C6)alkyl, (CH2)pORA, (CH2)pNRARB, (CH2)pC(═O)NRARB, (CH2)pC(═O)ORA;
each occurrence of R4 is independently halogen, hydroxy, aryl (e.g., phenyl), O(CH2)mORA, O(CH2)mO(CH2)mORA, C(═O)(C1-C6)alkyl, C(═O)ORA, C(═O)NRARB, —NRARB, —NRCCH2(CH2)pNRARB, NRC[CH2(CH2)pNRA]mCH2(CH2)nNRARB, O[CH2(CH2)pO]mCH2(CH2)nORA, OCH2(CH2)pNRARB, or O[CH2(CH2)pO]mCH2(CH2)nNRARB;
each occurrence of R6 is independently halogen, hydroxy, aryl (e.g., phenyl), S(C1-C6)alkyl, SRA, ORA, O(CH2)mORA, O(CH2)mO(CH2)mORA, C(═O)ORA, C(═O)NRARB, NRARB, O(CH2)mNRARB, O(CH2)mO(CH2)mNRARB, NRC(CH2)mNRARB, or NRC(CH2)mNRC(CH2)mNRARB, wherein said aryl or phenyl is optionally substituted by one or more groups which may be the same or different selected from halogen, hydroxy, (C1-C6)alkyl, (CH2)pORA, (CH2)pNRARB, (CH2)pC(═O)NRARB and (CH2)pC(═O)ORA;
each occurrence of RA and RB is independently:
hydrogen;
(C1-C6)alkyl, optionally substituted by one or more groups RD which may be the same or different;
(C2-C6)alkenyl or (C2-C6)alkynyl;
(C3-C7)cycloalkyl optionally substituted with (C1-C6)alkyl;
phenyl optionally substituted with from one to five groups which may be the same or different selected from halogen, —O(C1-C6)alkyl, —C(═O)O(C1-C6)alkyl, amino, alkylamino and dialkylamino;
or a heterocyclic ring which may be saturated or unsaturated containing five or six ring atoms and from one to three heteroatoms which may be the same or different selected from nitrogen, sulfur and oxygen;
or RA and RB, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to four groups which may be the same or different selected from the group consisting of alkyl, phenyl and benzyl;
each occurrence of RC is independently hydrogen or (C1-C6)alkyl;
p is an integer of 0, 1, 2, 3, 4, or 5;
and
m is an integer of 1, 2, 3, 4 or 5.

39 more elements