US 2009/0156465 A1Published application

Derivatives of beta-amino acid as dipeptidyl peptidase-iv inhibitors

OwnerJitendra A. Sattigeri, Shahadat Ahmed +11inventors

InventorsJitendra A. Sattigeri, Shahadat Ahmed, Murugaiah M.S. Andappan, Sachin Sethi, Lalima Sharma, Chanchal Kumar Pal, Sachin Ramesh Kandalkar, Dipak C. Mahajan, Kaushal Kishore, Sumati Bhatia, Anil G. Gadhave, Vinay S. Bansal, Joseph Alexanand Davis

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Abstract

The present invention relates to β-amino acid derivatives as dipeptidyl peptidase-IV inhibitors and the processes for the synthesis of the same. This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating diabetes, especially type 2 diabetes, as well as prediabetes, diabetic dyslipidemia, metabolic acidosis, ketosis, satiety disorders, and obesity. These inhibitors can also be used to treat conditions manifested by a variety of metabolic, neurological, anti-inflammatory, and autoimmune disorders like inflammatory disease, multiple sclerosis, rheumatoid arthritis; viral, cancer and gastrointestinal disorders. The compounds of this invention can also be used for treatment of infertility arising due to polycystic ovary syndrome.

Claims10

Dependent claims

Compounds having the structure of formula 1

including pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, polymorphs, prodrugs, metabolites or N-oxides thereof,
wherein
A is an aryl or heteroaryl group;
E and E′ are independently —(CRaRb)1— (wherein 1 is an integer of 1 to 2 and Ra and Rb are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocyclyl;
Ra and Rb can together form a ring, which can be optionally unsaturated);
and
R is selected from the groups a to c:
wherein
Rc is hydrogen or alkyl;
Rd is hydrogen, alkyl, aryl, heteroaryl, heterocyclyl or cycloalkyl;
Re is hydrogen, alkyl, halogen, cyano, carboxy, hydroxyl, alkoxy, carbonyl or amino;
a and b are an integer of 0-2;
J is a bond, —O—, —NRf—, —NRfCO—, —NRfCONRf—, —NRfSO2—, —NRfC(O)O—, or —OCONRf—, wherein Rf refers to hydrogen, alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl;
J1 is hydrogen, alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl (when J is —NRfSO2—, or NRfC(O)O—, then J1 is not hydrogen);
L is (CH2)p wherein p is an integer of 1-2;
M is CH or N;
Q is (CH2)q, O or S(O)q wherein q is an integer of 0-2;
R1 is —(CRaRb)m— wherein m is an integer of 0-1;
R2 is —NRf—, —O—, —CO—, —CS—, —CONRf—, —NRfCO—, —NRfCONRf—, —NRfSO2—, —NRfCOO—, or
—OCONRf—;
wherein Rf is defined as above;
R3 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocyclyl;
R7 is no atom, —CO—, —CS—, and —SO2—;
R8 is no atom, —O— or —NRf—;
and
R9 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl with the following provisos:
(i) when A, E, and E′ are defined as earlier, R as a-1 and a-2 (group a), R1 as —(CRaRb)m— {wherein m=0 or m=1 when a=b=1}, and R2 as —NRf—, then R3 cannot be a heteroaryl,
(ii) when A, E, and E′ are defined as earlier, R as a-1 (group a) {wherein a is an integer of 0 and b is an integer of 1}, R1 as —(CRaRb)m-{wherein m is an integer of 0}, and R3 as defined earlier, then R2 cannot be —CONRf,
(iii) when A, E, and E′ are defined as earlier, R as a-1 (group a) wherein a is an integer of 0 and b is an integer of 0-2, R2 as —O— and —NRf— and R3 as defined earlier, then R1 cannot be —(CRaRb)m— [wherein m is an integer of 1],
(iv) when A, E, and E′ are defined as earlier, R as b-1 (when M is N) and b-2 (group b) or a-4 (group a) wherein R7 and R8 are no atom, then R9 cannot be a heteroaryl, and
(v) when A, E, and E′ are defined as earlier, R as a-4 (group a), b-1 (when M is N), b-2, and b-3, (group b), and R7 as no atom, then R8 cannot be —O— or —NRf—.

28 more elements

A compound selected from the group consisting of

Compound no 1:
(3R)-3-Amino-N-[1-(morpholin-4-ylcarbonyl)piperidin-4-yl]-4-(2,4,5-trifluorophenyl)butanamide and its trifluoroacetic acid salt,
Compound no 2:
(3R)-3-Amino-N-{1-[(4-fluorophenyl)sulphonyl]piperidin-4-yl}-4-(2,4,5-triflu-orophenyl)butanamide and its 4-methylbenzenesulfonic acid salt,
Compound no 3:
(3R)-3-Amino-N-[1-(4-fluorobenzoyl)piperidin-4-yl]-4-(2,4,5-trifluorophenyl) butanamide and its 4-methylbenzenesulfonic acid salt,
Compound no 4:
N-{1-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-4-fluorobenzamide and its trifluoroacetic acid salt,
Compound no 5:
(3R)-3-Amino-N-[1-(methylsulphonyl)piperidin-4-yl]-4-(2,4,5-trifluorophenyl) butanamide and its 4-methylbenzenesulfonic acid salt,
Compound no 6:
(3R)-3-Amino-N-(3-hydroxy-1-adamantyl)-4-(2,4,5-trifluorophenyl) butanamide and its 4-methylbenzenesulfonic acid salt,
Compound no 7:
4-{1[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]amino}-N-(4-chloro phenyl)piperidine-1-carboxamide and its hydrochloride salt,
Compound no 8:
(3R)-3-Amino-N-[(1R,5S)-3-(2-thienylsulphonyl)-3-azabicyclo[3.1.0]hex-6-yl]-4-(2,4,5-trifluorophenyl)butanamide and its trifluoroacetic acid salt,
Compound no 9:
(3R)-3-Amino-N-[(1R,5S)-3-(4-cyanobenzoyl)-3-azabicyclo[3.1.0]hex-6-yl]-4-(2,4,5-trifluorophenyl)butanamide and its trifluoroacetic acid salt,
Compound no 10:
(3R)-3-Amino-N-[(1R,5S)-3-(2,6-difluorobenzoyl)-3-azabicyclo[3.1.0]hex-6-yl]-4-(2,4,5-trifluorophenyl)butanamide and its trifluoroacetic acid salt,
Compound no. 11:
N-{1-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-4-flu-orobenzenesulfonamide and its trifluoroacetic acid salt,
Compound no. 12:
N-{1-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}mor-pholine-4-carboxamide and its trifluoroacetic acid salt,
Compound no. 13:
1-{1-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-3-(4-chlorophenyl)urea and its trifluoroacetic acid salt,
Compound no. 14:
N-{1-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-3-fluoro-4-methoxybenzamide and its trifluoroacetic acid salt,
Compound no. 15:
N-{1-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-2-propanesulfonamide and its trifluoroacetic acid salt,
Compound no 16:
(3R)-3-Amino-N-[(1R,5S)-3-(4-trifluorobenzenesulphonyl)-3-azabicyclo [3.1.0]hex-6-yl]-4-(2,4,5-trifluorophenyl)butanamide and its trifluoroacetic acid salt,
Compound no 17:
(3R)-3-Amino-N-[(1R,5S)-3-(thiophene-2-carbonyl)-3-azabicyclo[3.1.0]hex-6-yl]-4-(2,4,5-trifluorophenyl)butanamide and its trifluoroacetic acid salt,
Compound no 18:
(3R)-3-Amino-N-[(1R,5S)-3-(ethanesulphonyl)-3-azabicyclo[3.1.0]hex-6-yl]-4-(2,4,5-trifluorophenyl)butanamide and its trifluoroacetic acid salt,
Compound no 19:
(3R)-3-Amino-N-[(1R,5S)-3-(4-methylbenznesulphonyl)-3-azabicyclo[3.1.0] hex-6-yl]-4-(2,4,5-trifluorophenyl)butanamide and its trifluoroacetic acid salt,
Compound no 20:
4-[({(3R)-1-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]pyrrolidin-3-yl}oxy)methyl]benzonitrile and its trifluoroacetic acid salt,
Compound no 21:
(2R)-4-{(3S)-3-[(4-Fluorobenzyl)oxy]pyrrolidin-1-yl}-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound no 22:
4-[({(3S)-1-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]pyrrolidin-3-yl}oxy)methyl]benzonitrile and its trifluoroacetic acid salt,
Compound No. 23:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-2,2,2-trifluoroethanesulfonamide and its trifluoroacetic acid salt,
Compound No. 24:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-4-cyanobenzenesulfonamide and its trifluoroacetic acid salt,
Compound No. 25:
N-{1-[3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-2,4-difluorobenzenesulfonamide and its trifluoroacetic acid salt,
Compound No. 26:
Methyl 5-[({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)sulfonyl]-4-methylthiophene-2-carboxylate,
Compound No. 27:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-1,3,5-trimethyl-1H-pyrazole-4-sulfonamide,
Compound No. 28:
methyl 4-[({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)sulfonyl]-2,5-dimethyl-3-furoate,
Compound No. 29:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-4-fluorobenzenesulfonamide,
Compound No. 30:
4-acetyl-N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl] piperidin-4-yl}benzenesulfonamide and its trifluoroacetic acid salt,
Compound No. 31:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-2,4-difluorobenzenesulfonamide and its trifluoroacetic acid salt,
Compound No. 32:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} methane sulfonamide and its trifluoroacetic acid salt,
Compound No. 33:
methyl 5-[({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl] piperidin-4-yl} amino) sulfonyl]-4-methylthiophene-2-carboxylate and its trifluoroacetic acid salt,
Compound No. 34:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} propane-2-sulfonamide and its trifluoroacetic acid salt,
Compound No. 35:
N-{(3S)-1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-3-yl}ethane sulfonamide and its trifluoroacetic acid salt,
Compound No. 36:
4-(1,3-dihydro-2H-isoindol-2-yl)-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 37:
N-{1-[3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}propanamide and its trifluoroacetic acid salt,
Compound No. 38:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}acetamide and its trifluoroacetic acid salt,
Compound No. 39:
N-{1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl}-4-fluorobenzamide,
Compound No. 40:
2-({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)-4,6-difluorobenzonitrile and its trifluoroacetic acid salt,
Compound No. 41:
2-({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)benzonitrile and its trifluoroacetic acid salt,
Compound No. 42:
4-({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)-2,6-difluorobenzonitrile and its 4-methylbenzenesulfonic acid salt,
Compound No. 43:
4-({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)-2,6-difluorobenzonitrile and its trifluoroacetic acid salt,
Compound No. 44:
2-({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)benzonitrile and its trifluoroacetic acid salt,
Compound No. 45:
4-({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)benzonitrile and its trifluoroacetic acid salt,
Compound No. 46:
4-({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)benzonitrile and its trifluoroacetic acid salt,
Compound No. 47:
4-({1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]piperidin-4-yl} amino)-2-(trifluoromethyl)benzonitrile and its trifluoroacetic acid salt,
Compound No. 48:
Ethyl ({(3S)-1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]pyrrolidin-3-yl}oxy)acetate and its trifluoroacetic acid salt,
Compound No. 49:
(2R)-4-oxo-4-[5-(2-thienylacetyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 50:
(2R)-4-oxo-4-[5-(trifluoroacetyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine and its hydrochloride salt,
Compound No. 51:
(2R)-4-oxo-4-(5-propionyl-2,5-diazabicyclo[2.2.1]hept-2-yl)-1-(2,4,5-trifluoro phenyl) butan-2-amine and its hydrochloride salt,
Compound No. 52:
5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-cyanophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its 4-methylbenzenesulfonic acid salt,
Compound No. 53:
(2R)-4-(5-acetyl-2,5-diazabicyclo[2.2.1]hept-2-yl)-4-oxo-1-(2,4,5-trifluoro-phenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 54:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-fluoro-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 55:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-methoxy-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 56:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-[4-(trifluoro-methyl)phenyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 57:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-benzyl-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 58:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-methyl-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 59:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-tert-butyl-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 60:
(2R)-4-{5-[(3-fluorophenyl)sulfonyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 61:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(3-fluoro-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 62:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-[2-(trifluoromethyl)phenyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 63:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2-methyl-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 64:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-nitro-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 65:
4-{(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-2-chlorobenzonitrile and its trifluoroacetic acid salt,
Compound No. 66:
2-{(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-6-fluorobenzonitrile and its trifluoroacetic acid salt,
Compound No. 67:
4-{(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-3-fluorobenzonitrile and its trifluoroacetic acid salt,
Compound No. 68:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-cyclohexyl-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 69:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(3-methoxy-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 70:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl) butanoyl]-N-(2-fluoro-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 71:
(2R)-4-[5-(ethylsulfonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 72:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,4-dimethoxyphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 73:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-isopropyl-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 74:
4-{5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-2,5-diazabicyclo-[2.2.1]hept-2-yl}-2-(trifluoromethyl)benzonitrile and its trifluoroacetic acid salt,
Compound No. 75:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-[4-(benzyl-oxy)phenyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 76:
(2R)-4-[5-(4-fluorobenzoyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 77:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(3,4,5-tri-methoxyphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 78:
5-[3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-fluorophenyl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 79:
(1S,4S)-5-[3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,6-diisopropyl phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 80:
methyl 2-[({(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}carbonyl)amino]benzoate and its trifluoroacetic acid salt,
Compound No. 81:
(2R)-4-oxo-4-[5-(2-thienylsulfonyl)-2,5-diaza-bicyclo[2.2.1]hept-2-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 82:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(5-chloro-2-methoxy phenyl)-2,5-diazabicyclo [2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 83:
4-({5-[(3R)-3-amino-4-(2,4,5-trifluoro phenyl)butanoyl]-2,5-diazabicyclo [2.2.1]hept-2-yl}sulfonyl)benzonitrile and its trifluoroacetic acid salt,
Compound No. 84:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,3-dichlorophenyl)-2,5-diazabicyclo [2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 85:
(2R)-4-{(1S,4S)-5-[(3,5-difluorophenyl) sulfonyl]-2,5-diazabicyclo [2.2.1]hept-2-yl}-4-oxo-1-(2,4,5-trifluorophenyl) butan-2-amine and its trifluoroacetic acid salt,
Compound No. 86:
(1S,4S)—N-(4-acetylphenyl)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl) butanoyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 87:
methyl 5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-2,5-diazabicyclo [2.2.1]heptane-2-carboxylate and its trifluoroacetic acid salt,
Compound No. 88:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,5-dimethoxyphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 89:
ethyl 5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-2,5-diazabicyclo [2.2.1]heptane-2-carboxylate and its trifluoroacetic acid salt,
Compound No. 90:
(2R)-4-oxo-4-[5-(propylsulfonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-1-(2,4,5-trifluoro-phenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 91:
(2R)-4-[5-(isopropylsulfonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluoro phenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 92:
(2R)-4-[5-(butylsulfonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluoro-phenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 93:
(2R)-4-oxo-4-[5-(phenylsulfonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 94:
(2R)-4-[5-(morpholin-4-ylcarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 95:
(2R)-4-oxo-4-(5-{[3-(trifluoromethoxy)phenyl]sulfonyl}-2,5-diazabicyclo [2.2.1]hept-2-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 96:
(2R)-4-[5-(methylsulfonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 97:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,6-difluoro-phenyl)-2,5-diazabicyclo [2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 98:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,4,6-trifluoro-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 99:
(1S,4S)—N-(3-acetylphenyl)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl) butanoyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 100:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,5-dichloro-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 101:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-isopropyl-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 102:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-butyl-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 103:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-ethoxy-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 104:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(3-ethyl-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 105:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2-isopropyl-6-methylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 106:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-mesityl-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 107:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-methoxy-2-methylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 108:
(1S,4S)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-phenoxy-phenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 109:
(2R)-4-[(1R,4R)-5-(cyclohexylcarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluorophenyl) butan-2-amine and its trifluoroacetic acid salt,
Compound No. 110:
(2R)-4-[(1R,4R)-5-(cyclopropyl carbonyl)-2,5-diazabicyclo [2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluorophenyl) butan-2-amine and its trifluoroacetic acid salt,
Compound No. 111:
(2R)-4-[(1R,4R)-5-(3,5-difluorobenzyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-amine and its trifluoroacetic acid salt,
Compound No. 112:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2-ethoxyphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 113:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2-ethylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 114:
methyl 3-[({(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)amino]benzoate and its trifluoroacetic acid salt,
Compound No. 115:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(4-ethylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 116:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(3-chloro-4-methylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 117:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-[3-(methylthio)phenyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 118:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,4-difluorophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 119:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2,4-dimethylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 120:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(3,4-dichlorophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 121:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-[4-chloro-3-(trifluoromethyl)phenyl]-2,5-diazabicyclo [2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 122:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(3-cyanophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 123:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-(2-isopropylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt,
Compound No. 124:
(1R,4R)-5-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-[3,5-bis-(trifluoromethyl)phenyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide and its trifluoroacetic acid salt.

245 more elements

Dependencies are inferred from the claim text.