Abstract: Indole derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD).

Abstract: A process for the production of heterocyclic quaternary ammonium salts or hydroxides is disclosed. The process comprises a continuous hydrogenation step, in which an unsaturated heterocyclic amine is reacted with hydrogen to form a saturated heterocyclic amine; a first continuous N-alkylation step, in which the saturated heterocyclic amine is alkylated to produce an intermediate saturated heterocyclic amine having an increased degree of substitution compared to the saturated heterocyclic amine; and one or more further N-alkylation steps in which the intermediate saturated heterocyclic amine is N-alkylated to the heterocyclic quaternary ammonium salt or hydroxide. A process of producing a saturated heterocyclic amine is also disclosed. The process comprises reacting an unsaturated heterocyclic amine with hydrogen in a vapour phase reaction at a pressure of not more than 70 bar and a temperature in the range of from 150° C. to 350° C. A process of N-alkylating a saturated heterocyclic amine is also disclosed.

Abstract: There is described a method of preparing a compound of formula I, and optical isomers thereof; in which R1 is hydrogen or a protecting group; said method comprising oxidizing verbenone and optical isomers thereof.

Abstract: There is described a method of preparing a compound of formula I, and optical isomers thereof; in which R1 is hydrogen or a protecting group; said method comprising oxidising verbenone and optical isomers thereof.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N-methyl-3-keto-3-(2-thienyl)-1-propanamine to (S)—N-methyl-3-hydroxy-3-(2-thienyl)-1-propanamine.

Abstract: The present disclosure provides acyltransferases useful for synthesizing therapeutically important statin compound.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N,N-dimethyl-3-keto-3-(2-thienyl)-1-ketopropanamine to (S)-N,N-dimethyl-3-hydroxy-3-(2-thienyl)-1-propanamine.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N,N-dimethyl-3-keto-3-(2-thienyl)-1-ketopropanamine to (S)—N,N-dimethyl-3-hydroxy-3-(2- thienyl)-1-propanamine.

Abstract: The present disclosure provides acyltransferases useful for synthesizing therapeutically important statin compound.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N-methyl-3-keto-3-(2-thienyl)-1-propanamine to (S)—N-methyl-3-hydroxy-3-(2-thienyl)-1-propanamine.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N-methyl-3-keto-3-(2-thienyl)-1-propanamine to (S)—N-methyl-3-hydroxy-3-(2-thienyl)-1-propanamine.

Abstract: Methods for the improved acylation of chemical substrates using LovD acyltransferases, thioesters having acyl groups, and (i) thiol scavengers and/or (ii) precipitating agents are presented. An improved method for the production of simvastatin using (i) activated charcoal as a thiol scavenger and/or (ii) ammonium hydroxide as a precipitating agent is also presented.

Abstract: The present disclosure provides acyltransferases useful for synthesizing therapeutically important statin compound

Abstract: Presently provided are methods for (a) modulating an activity of indoleamine 2,3-dioxygenase comprising contacting an indoleamine 2,3-dioxygenase with a modulation effective amount of a compound as described in one of the aspects described herein; (b) treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression in a subject in need thereof, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (c) treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (d) enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent and a compound as described in one of the aspects described herein; (e) treating tumor-specific immunosuppression associated with cancer compris

Abstract: A method of determining velocity of a shaft is provided. The method includes receiving a first shaft position signal and a second shaft position signal. Derivatives of each of the first shaft position signal and the second shaft position signal are computed, as are squares of each of the derivatives, a summation of the squares, and a square root of the summation. The velocity is output as a result of the square root.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N-methyl-3-keto-3-(2-thienyl)-1-propanamine to (S)—N-methyl-3-hydroxy-3-(2-thienyl)-1-propanamine.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N,N-dimethyl-3-keto-3-(2-thienyl)-1-ketopropanamine to (S)—N,N-dimethyl-3-hydroxy-3-(2-thienyl)-1-propanamine.

Abstract: A method for implementing control signal linearization for an electric motor is disclosed. In an exemplary embodiment, the method includes receiving a desired voltage command to be applied to the motor and determining whether the magnitude of the desired voltage command falls between a first value and a second value. If the magnitude of the desired voltage command falls between the first value and the second value, then modulating a voltage command between the first and the second value over a determined sample period, thereby resulting in the application of a modulated voltage command to the motor.

Abstract: A method for controlling a voltage mode controlled electric machine comprising: receiving a torque value representative of a desired torque; obtaining a speed value indicative of a rotational velocity of the electric machine; acquiring a phase advance value indicative of a desired phase advance angle; generating a voltage command responsive to the torque value, the position value; the generating is responsive to the torque value, the speed value, and the phase advance value.

Abstract: A method and apparatus for determining the velocity of a rotating device is described herein. The apparatus includes a magnet assembly affixed to a rotating shaft of a rotating device and a circuit assembly. The circuit assembly includes a circuit interconnection having a sense coil and sensors affixed thereto. The circuit assembly is adapted to be in proximity to the magnet assembly, wherein the magnet assembly combines with the circuit assembly to form an air core electric machine such that voltages generated from the sense coil exhibits an amplitude proportional to the velocity.