# US 10,246,429 B2 · Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use

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- Number: US 10,246,429 B2
- Document ID: US10246429B2
- Status: Granted
- Kind: B2
- Application number: 15/749,895
- Filed: 2016-08-04
- Published: 2018-08-09
- Granted: 2019-04-02
- Earliest claimed: 2015-08-06
- Assignees: Amgen Inc.
- Applicants: Amgen Inc.
- Inventors: Jennifer R. Allen; Albert Amegadzie; Matthew P. Bourbeau; James A. Brown; Ning Chen; Michael J. Frohn; Longbin Liu; Qingyian Liu; Liping H. Pettus; Wenyuan Qian; Corey M. Reeves; Aaron C. Siegmund
- Web page: https://patentgrep.com/patent/US10246429B2

## CPC

- C07D 279/08: condensed with carbocyclic rings or ring systems
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07D 417/10: linked by a carbon chain containing aromatic rings
- C07D 417/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 491/056: with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
- C07D 491/08: Bridged systems
- C07D 491/107: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D 498/10: Spiro-condensed systems
- C07F 7/0812: {comprising a heterocyclic ring}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A7, and each of Ra, Rb, R1, R2, R3, R8 R9 and R10 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions.

## Claims

### Claim 1

A compound of Formula I
or a stereoisomer, tautomer, hydrate, solvate or a pharmaceutically acceptable salt thereof, wherein
A4 is CR4 or N;
A5 is CR5 or N;
A6 is CR6 or N;
A7 is CR7 or N, provided that no more than two of A4, A5, A6, and A7 are N;
each of Ra and Rb, independently, is H, F, Cl, C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein each of the C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, and C1-6-alkyl portion of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, and —C(O)C1-6-alkyl are optionally substituted with 1-4 substituents independently selected from F, oxo, or OH;
R1 is H, F, Cl, C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, —C(O)NH2, —CH═CHC(O)NH2, —CH═CHC(O)NHC1-6-alkyl, —CH═CHC(O)N(C1-6-alkyl)2, —CH═CHC(O)NHC1-6-alkyl-OC1-6-alkyl, —CH═CHC(O)-heterocyclyl, —CH═C(CH3)C(O)-heterocyclyl, —CH═CHC(O)2H, —CH═CHC(O)OC1-6-alkyl, —CH═CHCH2OH, C1-6-alkyl-C(O)NHC1-6-alkyl, C1-6-alkyl-C(O)N(C1-6-alkyl)2, —C(O)C1-6-alkyl, —C(O)C2-6-alkenyl, —C(O)OH, —C(O)OC1-6-alkyl, —C(O)NHC1-6-alkyl, —C(O)N(C1-6-alkyl)2, —C(O)NHC3-6-cycloalkyl, —C(O)NH-aryl, —C(O)NH-heterocyclyl, —C(O)NHOC1-6-alkyl, —C(O)N(C1-6-alkyl)OC1-6-alkyl, —C(O)-heterocyclyl, —CH2-heteroaryl, or heteroaryl, wherein the heterocyclyl groups of the —CH═CHC(O)-heterocyclyl, —CH═C(CH3)C(O)-heterocyclyl, —C(O)— heterocyclyl, and —C(O)NH-heterocyclyl groups are fully or partially saturated 3-, 4-, 5-, or 7-membered monocyclic rings or 6-, 7-, 8-, 9-, or 10-membered bicyclic rings that include 1 heteroatom selected from N, O, or S if the ring is a 3-membered ring, that include 1 or 2 heteroatoms independently selected from N, O, or S if the ring is a 4- or 5-membered ring, and include 1, 2, or 3 heteroatoms independently selected from N, O, or S if the ring is a 6-, 7-, 8-, 9-, or 10-membered ring, wherein the heteroaryl groups of the —CH2-heteroaryl and heteroaryl groups is a 5- or 6-membered ring that includes 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S, wherein the aryl group of the —C(O)NH-aryl group is a phenyl or naphthyl group, wherein each of the C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, and C1-6-alkyl and C2-6-alkenyl portions of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, C(O)C1-6-alkyl, —C(O)C2-6-alkenyl, —CH═CHC(O)NHC1-6-alkyl, —C(O)NHC1-6-alkyl, —C(O)N(C1-6-alkyl)2, and C1-6-alkyl-C(O)NHC1-6-alkyl groups is optionally substituted with 1-4 substituents independently selected from F, CN, oxo, or OH, and further wherein each of the heterocyclyl groups of the —CH═CHC(O)-heterocyclyl, —CH═C(CH3)C(O)-heterocyclyl, —C(O)heterocyclyl, and —C(O)NH-heterocyclyl groups is optionally substituted with 1-4 substituents independently selected from methyl, F, OH, oxo, —CN, OCH3, —CH2OC1-6-alkyl, —C(O)C1-6-alkyl, —C(O)OC1-6-alkyl, —CH2OH, —NH2, —NHC1-6-alkyl, —N(C1-6-alkyl)2, —CF3, phenyl, or —CH2—C3-6-cycloalkyl and further wherein each of the heteroaryl groups of the —CH2-heteroaryl and heteroaryl groups and the aryl group of the —C(O)NH-aryl group is optionally substituted with 1-3 substituents independently selected from halo, methyl, or OH;
R2 is H, F, Cl, C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, —C(O)NH2, —CH═CHC(O)NHC1-6-alkyl, —CH═CHC(O)2H, —CH═CHCH2OH, C1-6-alkyl-C(O)NHC1-6-alkyl, —C(O)C1-6-alkyl, or —C(O)C2-6-alkenyl, wherein each of the C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, and C1-6-alkyl and C2-6-alkenyl portion of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, C(O)C1-6-alkyl, —C(O)C2-6-alkenyl, —CH═CHC(O)NHC1-6-alkyl, and C1-6-alkyl-C(O)NHC1-6-alkyl, is optionally substituted with 1-4 substituents independently selected from F, CN, oxo, or OH;
R3 is C1-4-alkyl, CH2OC1-4-alkyl, CH2OH, C1-4haloalkyl or cyclopropyl, wherein each of the C1-4-alkyl, CH2OC1-4-alkyl, C1-4-haloalkyl, and cyclopropyl is optionally substituted with 1-4 F atoms;
each of R4, R5, R6 and R7, independently, is H, halo, haloalkyl, haloalkoxyl, C1-4-alkyl, CN, OH, OC1-4-alkyl, S(O)oC1-4-alkyl, NHC1-4-alkyl, C(O)C1-4-alkyl, C(O)OC1-4-alkyl, or CH2OH;
R8 is selected from H, F, Cl, or C1-3-alkyl;
one of R9 and R10 is selected from F or H and the other of R9 and R10 is a fully or partially unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 8-, 9-, or 10-membered bicyclic ring formed of carbon atoms, said ring optionally including 1-4 heteroatoms if monocyclic or 1-5 heteroatoms if bicyclic, said heteroatoms selected from O, N, or S, wherein the ring is optionally substituted, independently, with 1-5 substituents of R11;
each R11, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, SF5, acetyl, —C(O)NHC1-6-alkyl, —OCH2C(O)NHC1-6-alkyl, —OCH2C(O)N(C1-6-alkyl)2, —OCH2CH2-pyrrolidinonyl, oxo, cyclopropylmethoxy, 2-propynyloxy, 2-butynyloxy, 2-pentyloxy, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, C1-6-alkylamino-, C1-6-dialkylamino-, C1-6-alkoxyl, C1-6-thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolyl, pyrrolidinyl, piperazinyl, oxetan-3-yl, imidazo-pyridinyl, dioxolyl, or —OCH2-heteroaryl, wherein the heteroaryl group of the —OCH2-heteroaryl group is a 5- or 6-membered ring that includes 1, 2, 3, or 4 heteroatoms selected from N, O, or S, and further wherein each of the cyclopropylmethoxy, 2-propynyloxy, 2-butynyloxy, 2-pentyloxy, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, C1-6-alkylamino-, C1-6-dialkylamino-, C1-6-alkoxyl, C1-6-thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetan-3-yl, dioxolyl, or —OCH2-heteroaryl is optionally substituted independently with 1-5 substituents of F, Cl, Br, CN, NO2, NH2, OH, oxo, CF3, CHF2, CH2F, methyl, methoxy, ethyl, ethoxy, CH2CF3, CH2CHF2, propyl, propoxy, isopropyl, isopropoxy, cyclopropyl, butyl, butoxyl, cyclobutyl, isobutoxy, tert-butoxy, isobutyl, sec-butyl, tert-butyl, trimethylsilyl, cyclopentyl, cyclohexyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, thienyl, furyl, pyrrolyl, tetrahydropyranyl, pyrrolidinyl, or oxetan-3yl; and
the subscript o is selected from 0, 1, or 2.

### Claim 2 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IA

### Claim 3 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IB

### Claim 4 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein Ra and Rb are both —H.

### Claim 5 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R2 is —H.

### Claim 6 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein A6 is CR6 and R6 is —H.

### Claim 7 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein A7 is CR7 and R7 is —H.

### Claim 8 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein A4 is CR4.

### Claim 9 (depends on 8)

The compound according to claim 8, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R4 is —H.

### Claim 10 (depends on 8)

The compound according to claim 8, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R4 is —F.

### Claim 11 (depends on 8)

The compound according to claim 8, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R4 is —OCH3.

### Claim 12 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R8 is —H.

### Claim 13 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R8 is —F.

### Claim 14 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R3 is selected from C1-4-alkyl or C1-4-haloalkyl.

### Claim 15 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R3 is selected from —CH3 or —CH2F.

### Claim 16 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein A5 is CR5.

### Claim 17 (depends on 16)

The compound according to claim 16, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R5 is —H.

### Claim 18 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein A5 is N.

### Claim 19 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein one of R9 and R10 is —F.

### Claim 20 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R1 is selected from substituted or unsubstituted —CH2OC1-6-alkyl, substituted or unsubstituted —S(O)oC1-6-alkyl, —C(O)NH2, substituted or unsubstituted —C(O)C1-6-alkyl, substituted or unsubstituted —C(═O)NHC1-6-alkyl, substituted or unsubstituted —C(═O)N(C1-6-alkyl)2, or substituted or unsubstituted —C(O)-heterocyclyl.

### Claim 21 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R1 is selected from

### Claim 22 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein one of R9 and R10 is —F and the other of R9 and R10 is selected from

### Claim 23 (depends on 22)

The compound according to claim 22, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R10 is —F.

### Claim 24 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein one of R9 and R10 is —F and the other of R9 and R10 is selected from a substituted or unsubstituted thienyl, a substituted or unsubstituted thiazolyl, a substituted or unsubstituted pyridinyl, a substituted or unsubstituted pyrazinyl, a substituted or unsubstituted pyrimidinyl, a substituted or unsubstituted pyridazinyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted imidazo[1,2-a]pyridinyl, a substituted or unsubstituted pyrido[3,4-b]pyrazinyl, a substituted or unsubstituted 2,3-dihydro-[1,4]dioxino[2,3-c]pyridinyl, or a substituted or unsubstituted 6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidinyl group.

### Claim 25 (depends on 24)

The compound according to claim 24, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein the substituted or unsubstituted thienyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyridazinyl, substituted or unsubstituted phenyl, substituted or unsubstituted imidazo[1,2-a]pyridinyl, substituted or unsubstituted pyrido[3,4-b]pyrazinyl, substituted or unsubstituted 2,3-dihydro-[1,4]dioxino[2,3-c]pyridinyl, or substituted or unsubstituted 6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidinyl of the R9 or R10 groups are independently substituted with 1-3 substituents selected from —Cl, —Br, —F, —CN, cyclopropylmethoxy, 2-propynyloxy, 2-butynyloxy, C1-6-alkyl, C2-6-alkynyl, C1-6-alkoxy, oxetan-3-yl, or —O—CH2-heteroaryl, and further wherein each of the 2-propynyloxy, C1-6-alkyl, C2-6-alkynyl, C1-6-alkoxy, or —O—CH2-heteroaryl is optionally substituted independently with 1-5 substituents of F, CN, OH, oxo, methyl, cyclopropyl, cyclobutyl, trimethylsilyl, or oxetanyl.

### Claim 26 (depends on 24)

The compound according to claim 24, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein R10 is —F.

### Claim 27 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IC
wherein
A5 is CR5 or N;
Ra is —H;
Rb is —H;
R2 is —H;
R3 is selected from C1-4-alkyl or C1-4-haloalkyl; and
R8 is —H.

### Claim 28 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula ID
wherein
A5 is CR5 or N;
Ra is —H;
Rb is —H;
R2 is —H;
R3 is selected from C1-4-alkyl or C1-4-haloalkyl; and
R8 is —H.

### Claim 29 (depends on 1)

The compound according to claim 1, or the stereoisomer, tautomer, hydrate, solvate or the pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IE
wherein
A5 is CR5 or N;
Ra is —H;
Rb is —H;
R2 is —H;
R3 is selected from C1-4-alkyl or C1-4-haloalkyl; and
R8 is —H.

### Claim 30 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from
(1S,5S,6S)-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-(fluoromethyl)-1-(methoxymethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(5-((E)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-(fluoromethyl)-1-(methoxymethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(pyrrolidin-1-yl)methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-methoxypyridin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(pyrrolidin-1-yl)methanone;
(1S,5S,6S)-methyl 3-amino-5-(5-((Z)-2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(pyrrolidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(cyclopropylethynyl)pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-ethynylpyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-methyl 3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(azetidin-1-yl)methanone;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)methanol;
2-((1R,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)acetonitrile;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N-(3-hydroxybutyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(2-methylazetidin-1-yl)methanone;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((S)-2-(methoxymethyl)pyrrolidin-1-yl)methanone;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-N-phenyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((S)-2-methylazetidin-1-yl)methanone;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((R)-2-methylazetidin-1-yl)methanone;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N-cyclopropyl-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(3,3-difluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(azetidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((S)-3-hydroxypyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((R)-3-fluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((S)-3-fluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-N-(tetrahydro-2H-pyran-4-yl)-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(isoindoline-2-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
(R)-methyl 1-((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carbonyl)pyrrolidine-2-carboxylate;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(4-phenylpiperazine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(2-oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((2R,5R)-2,5-dimethylpyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((R)-3-(dimethylamino)pyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((4aS,8aR)-decahydroisoquinoline-2-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(1,3,3-trimethyl-6-azabicyclo[3.2.1]octane-6-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(3,5-dimethylpiperidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(2-methylpyrrolidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(4-(trifluoromethyl)piperidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(3-phenylpiperidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(4-(cyclopropylmethyl)piperazine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(5-oxo-1,4-diazepane-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(3-cyanopiperidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(3-oxopiperazine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(3-methylpiperidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(piperidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(4-methylpiperidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-methyl 3-amino-5-(5-((Z)-2-(5-bromopyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
(1S,5S,6S)-methyl 3-amino-5-(5-((Z)-2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
(1S,5S,6S)-methyl 3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-oxopropoxy)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(-1-(oxazol-2-yl)ethoxy)pyrazin-2-yl)vinyl)phenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-bromopyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(cyanomethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(cyclopropylethynyl)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)-5-methylnicotinonitrile;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxazol-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-bromopyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-1-yn-1-yl)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(cyclopropylethynyl)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((trimethyl silyl)ethynyl)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-ethynylpyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept- 3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(4-cyanophenyl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyrimidin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(6-cyanopyridin-3-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(4-cyano-2-fluorophenyl)-2-fluorovinyl)-2-fluorophenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(2-cyanopyrimidin-5-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(6-cyanopyridazin-3-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-methyl 3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
(1S,5S,6S)-methyl 3-amino-5-(5-((E)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((E)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
6-((Z)-2-(5-((1S,5S,6S)-3-amino-1-((R)-3-fluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(5-((1S,5S,6S)-3-amino-1-((S)-3-fluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(5-((1S,5S,6S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(5-((1S,5S,6S)-3-amino-1-((R)-3-fluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-6-methoxypyridin-3-yl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-1-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide; or
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(4-cyanophenyl)-1-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide.

### Claim 31 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from
5-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile;
5-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(piperidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile;
5-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((S)-3-fluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile;
5-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((R)-3-fluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile;
5-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(pyrrolidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-ethynylpyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-methoxyethoxy)pyrazin-2-yl)vinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(cyclopropylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxetan-3-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(2,2-difluoroethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(54(S)-1-methoxypropan-2-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(2,2-difluorocyclopropyl)methoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(54(5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((3-methyl-1,2,4-oxadiazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((3-methylisoxazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanothiazol-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanothiophen-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(4-cyanophenyl)-1-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(trifluoromethyl)pyridin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyano-3-methylpyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxazol-5-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1R,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-1-(methyl sulfonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1R,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((5-methyl-1,3,4-oxadiazol-2-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-1-(methyl sulfonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1R,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-1-(methylsulfonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1R,5S,6S)-5-(5-((Z)-2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-1-(methylsulfonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1R,5S,6S)-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-1-(methylsulfonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1R,5S,6S)-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-1-(methylsulfonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
6-((Z)-2-(3-((1R,5S,6S)-3-amino-5-methyl-1-(methylsulfonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
1-((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)ethanone;
1-((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)ethanone;
1-((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)ethanone;
1-((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)ethanone;
6-((Z)-2-(3-((1S,5S,6S)-1-acetyl-3-amino-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carbonitrile;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carbonitrile;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carbonitrile;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(6-cyanoimidazo[1,2-a]pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(pyrido[3,4-b]pyrazin-7-yl)vinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-methyl 3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2,3-difluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
6-((Z)-2-(3-((1S,5S,6R)-3-amino-7,7-difluoro-1-(hydroxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
((1S,5S,6R)-3-amino-5-(5-((Z)-2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-7,7-difluoro-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)methanol;
((1S,5S,6R)-3-amino-7,7-difluoro-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)methanol;
5-((Z)-2-(3-((1S,5S,6R)-3-amino-7,7-difluoro-1-(hydroxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile;
((1S,5S,6R)-3-amino-5-(5-((Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-7,7-difluoro-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)methanol;
(1S,5S,6R)-methyl 3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-7,7-difluoro-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate;
6-((Z)-2-(3-((1S,5S,6R)-3-amino-7,7-difluoro-1-(2-hydroxypropan-2-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6R)-3-amino-7,7-difluoro-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(5-((1S,5S,6S)-3-amino-1-(3,3-difluoropyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(5-((1S,5S,6S)-3-amino-1-(4,4-difluoropiperidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-5-(5-((Z)-2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(5-((Z)-2-(5-((S)-but-3-yn-2-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((S)-2-methoxypropoxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(5-((Z)-2-(5-(2,2-difluoroethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(3,3,3-trifluoropropoxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-fluoroethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(5-((Z)-2-(5-(cyclopropylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(5-((Z)-2-(5-(cyclobutylmethoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxetan-3-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-isobutoxypyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,65)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((5-methylisoxazol-3-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((3-methylisoxazol-5-yl)methoxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((1,1,1-trifluoropropan-2-yl)oxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((1R,5R)-3,7-dioxa-9-azabicyclo[3.3.1]nonan-9-yl)methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((S)-3-fluoropyrrolidin-1-yl)methanone;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-N-(2,2-difluoroethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((R)-3-methylmorpholino)methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((1R,5R)-3,7-dioxa-9-azabicyclo[3.3.1]nonan-9-yl)methanone;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylic acid;
(1S,5S,6S)-5-(54Z)-2-(5-chloropyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2-oxopropoxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
6-((Z)-2-(5-((1S,5S,6S)-3-amino-5-methyl-1-((R)-3-methylmorpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(2,2,3,3-tetrafluoropropoxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-methyl 3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxylate methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((R)-3-fluoropyrrolidin-1-yl)methanone;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyrazin-2-yl)-2-fluorovinyl)-2-fluoropyridin-3-yl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((R)-3-fluoropyrrolidin-1-yl)methanone;
6-((Z)-2-(5-((1S,5S,6S)-3-amino-1-((1R,5R)-3,7-dioxa-9-azabicyclo[3.3.1]nonane-9-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-6-fluoropyridin-3-yl)-1-fluorovinyl)nicotinonitrile;
5-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazine-2-carbonitrile;
(1S,5S,6S)-3-amino-N-(2,2-difluoroethyl)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)pyridin-3-yl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
(1S,5S,6S)-3-amino-N-(2,2-difluoroethyl)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((S)-3-fluoropyrrolidin-1-yl)methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((R)-3-methylmorpholino)methanone;
(1S,5S,6S)-5-(5-((Z)-2-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((2 S,3 S)-3-fluoro-2-methylpyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((2R,3R)-3-fluoro-2-methylpyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(2,5-dioxa-8-azaspiro[3.5]nonane-8-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((S)-3-hydroxy-3-methylpyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((R)-3-hydroxy-3-methylpyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((1S,6R)-2-oxa-5-azabicyclo[4.1.0]heptane-5-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((1R,6S)-2-oxa-5-azabicyclo[4.1.0]heptane-5-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((3 S,5R)-3,5-dimethylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((3R,5R)-3,5-dimethylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((S)-2-isopropylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((R)-2-isopropylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(4-oxa-7-azaspiro[2.5]octane-7-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(4-oxa-7-azaspiro[2.5]octane-7-6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(7-oxa-2-azaspiro[3.5]nonane-2-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-((S)-2-methylmorpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((R)-3-isopropylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((2 S,6S)-2,6-dimethylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(3,3-difluoropiperidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(4,4-difluoropiperidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(4-fluoropiperidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(1-oxa-6-azaspiro[3.4]octane-6-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((S)-3-(methoxymethyl)morpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((2 S,5S)-2,5-dimethylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((2R,5R)-2,5-dimethylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(8-oxa-5-azaspiro[3.5]nonane-5-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-(3,3-dimethylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((R)-3-hydroxypyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((S)-3-ethylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((S)-3-ethylmorpholine-4-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-1-((2S,3R)-3-hydroxy-2-methylpyrrolidine-1-carbonyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(2-phenylpyrrolidine-1-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(pyridin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxetan-3-yl)pyridin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(5-methyloxazol-2-yl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-1-(5-methyloxazol-2-yl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
6-((E)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-ethynylpyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((trimethyl silyl)ethynyl)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-ethynylpyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-chloropyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(cyclopropylethynyl)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((trimethyl silyl)ethynyl)pyridin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((E)-2-(5-bromopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(cyclopropylethynyl)pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(cyclopropylethynyl)pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(3,3-dimethylbut-1-yn-1-yl)pyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(pent-1-yn-1-yl)pyridin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(3-hydroxyprop-1-yn-1-yl)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(3-fluoroprop-1-yn-1-yl)pyrazin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide; or
(1S,5S,6S)-3-Amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(trifluoromethoxy)pyridin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide.

### Claim 32

A compound, or a pharmaceutically acceptable salt thereof, selected from
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((E)-2-fluoro-2-iodovinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-4-phenylbut-1-en-3-yn-1-yl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluorovinyl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoropent-1-en-3-yn-1-yl)phenyl)-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide;
(1S,5S,6S)-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(oxetan-2-ylmethoxy)pyrazin-2-yl)vinyl)phenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
(1S,5S,6S)-5-(5-((Z)-2-(5-((3,3-difluorocyclobutyl)methoxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(4-methyl-4,5-dihydrooxazol-2-yl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
6-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-((R)-5-methyl-4,5-dihydrooxazol-2-yl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)nicotinonitrile;
3-(5-((Z)-2-(3-((1S,5S,6S)-3-amino-5-methyl-1-(morpholine-4-carbonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-1-fluorovinyl)pyrazin-2-yl)oxazolidin-2-one;
((1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(azetidin-1-yl)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone;
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-cyanopyridin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-N-(2,2-dimethoxyethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide; or
(1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-((3-methyloxetan-3-yl)ethynyl)pyridin-2-yl)vinyl)phenyl)-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide.

### Claim 33 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from

### Claim 34 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from

### Claim 35 (depends on 1)

A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable excipient.

### Claim 36 (depends on 1)

A method of reducing beta amyloid peptide levels in the cerebral spinal fluid of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 1.

### Claim 37 (depends on 1)

A method of treating Alzheimer's disease, cognitive impairment or a combination thereof in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 1.

### Claim 38 (depends on 1)

A method of treating a neurological disorder selected from mild cognitive impairment, Down's syndrome, Hereditary cerebral hemorrhage with Dutch-type amyloidosis, cerebral amyloid angiopathy, degenerative dementia, dementia associated with Parkinson's disease, dementia associated with supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease or a combination thereof in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 1.

### Claim 39 (depends on 1)

A method of reducing the formation of plaque on the brain of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 1.

### Claim 40 (depends on 30)

A pharmaceutical composition comprising the compound according to claim 30 and a pharmaceutically acceptable excipient.

### Claim 41 (depends on 30)

A method of reducing beta amyloid peptide levels in the cerebral spinal fluid of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 30.

### Claim 42 (depends on 30)

A method of treating Alzheimer's disease, cognitive impairment or a combination thereof in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 30.

### Claim 43 (depends on 30)

A method of treating a neurological disorder selected from mild cognitive impairment, Down's syndrome, Hereditary cerebral hemorrhage with Dutch-type amyloidosis, cerebral amyloid angiopathy, degenerative dementia, dementia associated with Parkinson's disease, dementia associated with supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease or a combination thereof in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 30.

### Claim 44 (depends on 30)

A method of reducing the formation of plaque on the brain of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 30.

### Claim 45 (depends on 31)

A pharmaceutical composition comprising the compound according to claim 31 and a pharmaceutically acceptable excipient.

### Claim 46 (depends on 31)

A method of reducing beta amyloid peptide levels in the cerebral spinal fluid of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 31.

### Claim 47 (depends on 31)

A method of treating Alzheimer's disease, cognitive impairment or a combination thereof in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 31.

### Claim 48 (depends on 31)

A method of treating a neurological disorder selected from mild cognitive impairment, Down's syndrome, Hereditary cerebral hemorrhage with Dutch-type amyloidosis, cerebral amyloid angiopathy, degenerative dementia, dementia associated with Parkinson's disease, dementia associated with supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease or a combination thereof in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 31.

### Claim 49 (depends on 31)

A method of reducing the formation of plaque on the brain of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 31.

### Claim 50 (depends on 32)

A pharmaceutical composition comprising the compound according to claim 32 and a pharmaceutically acceptable excipient.

### Claim 51 (depends on 32)

A method of reducing beta amyloid peptide levels in the cerebral spinal fluid of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 32.

### Claim 52 (depends on 32)

A method of treating Alzheimer's disease, cognitive impairment or a combination thereof in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 32.

### Claim 53 (depends on 32)

A method of treating a neurological disorder selected from mild cognitive impairment, Down's syndrome, Hereditary cerebral hemorrhage with Dutch-type amyloidosis, cerebral amyloid angiopathy, degenerative dementia, dementia associated with Parkinson's disease, dementia associated with supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease or a combination thereof in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 32.

### Claim 54 (depends on 32)

A method of reducing the formation of plaque on the brain of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to claim 32.